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Program ACTIVE II: Design and Methods for a Multi-Center Community-Based Depression Treatment for Rural and Urban Adults with Type 2 Diabetes

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Objective: Depression affects one in four adults with type 2 diabetes (T2DM) and is associated with worsened diabetes complications, increased health care costs and early mortality. Rural and low-income urban areas, including the Appalachian region, represent an epicenter of the T2DM epidemic. Program ACTIVE II is a comparative effectiveness treatment trial designed to test whether a combination of cognitive behavioral therapy (CBT) and community-based exercise (EXER) will offer greater improvements in diabetes and depression outcomes compared to individual treatment approaches and usual care (UC). The secondary aims are to assess changes in cardiovascular risk factors across groups and to conduct a cost-effectiveness analysis of predicted incidence of cardiovascular complications across groups. Methods: The study is a 2-by-2 factorial randomized controlled trial consisting of 4 treatment groups: CBT alone, EXER alone, combination of CBT and EXER, and UC. Adults with T2DM for > 1 year and who meet DSM-IVTR criteria for Major Depressive Disorder (MDD) are eligible to participate at two rural Appalachian sites (southeastern Ohio and West Virginia) and one urban site (Indianapolis). This type II behavioral translation study uses a community-engaged research (CEnR) approach by incorporating community fitness centers and mental health practices as interventionists. Conclusions: This is the first study to evaluate the comparative effectiveness of combined CBT and exercise in the treatment of depression using community-based intervention delivery. This approach may serve as a national model for expanding depression treatment for patients with T2DM.
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Program ACTIVE II: Design and Methods for a Multi-Center
Community-Based Depression Treatment for Rural and Urban
Adults with Type 2 Diabetes
Mary de Groot1,*, Jay Shubrook2, Frank Schwartz3, W. Guyton Hornsby Jr4, Yegan Pillay5,
and Chandan Saha1
1Indiana University School of Medicine, USA
2Touro University School of Medicine, USA
3Ohio University Heritage College of Osteopathic Medicine, USA
4West Virginia University School of Medicine, USA
5Ohio University, USA
Abstract
Objective—Depression affects one in four adults with type 2 diabetes (T2DM) and is associated
with worsened diabetes complications, increased health care costs and early mortality. Rural and
low-income urban areas, including the Appalachian region, represent an epicenter of the T2DM
epidemic. Program ACTIVE II is a comparative effectiveness treatment trial designed to test
whether a combination of cognitive behavioral therapy (CBT) and community-based exercise
(EXER) will offer greater improvements in diabetes and depression outcomes compared to
individual treatment approaches and usual care (UC). The secondary aims are to assess changes in
cardiovascular risk factors across groups and to conduct a cost-effectiveness analysis of predicted
incidence of cardiovascular complications across groups.
Methods—The study is a 2-by-2 factorial randomized controlled trial consisting of 4 treatment
groups: CBT alone, EXER alone, combination of CBT and EXER, and UC. Adults with T2DM
for > 1 year and who meet DSM-IVTR criteria for Major Depressive Disorder (MDD) are eligible
to participate at two rural Appalachian sites (southeastern Ohio and West Virginia) and one urban
site (Indianapolis). This type II behavioral translation study uses a community-engaged research
(CEnR) approach by incorporating community fitness centers and mental health practices as
interventionists.
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
*Corresponding author: Mary de Groot, Ph.D., Associate Professor, Indiana University School of Medicine, 410 W. 10th St., Suite
1140, Indianapolis, IN 46202, USA, Tel: (317) 278-1965; Fax: (317) 278-1750; mdegroot@iu.edu.
Author Contributions
All authors (MdG, JS, FS, WGH, YP) contributed to the study design, writing the manuscript and reviewing and editing all portions of
the manuscript.
Dr. de Groot and the co-authors serve as the guarantors of the manuscript and take full responsibility for the work as a whole including
the study design, access to data and decision to submit and publish the manuscript.
HHS Public Access
Author manuscript
J Diabetes Res Ther
. Author manuscript; available in PMC 2016 August 04.
Published in final edited form as:
J Diabetes Res Ther
. 2015 August ; 1(2): .
Author Manuscript Author Manuscript Author Manuscript Author Manuscript
Conclusions—This is the first study to evaluate the comparative effectiveness of combined CBT
and exercise in the treatment of depression using community-based intervention delivery. This
approach may serve as a national model for expanding depression treatment for patients with
T2DM.
Introduction
Nearly one in 10 Americans has diabetes and current projections estimate diabetes will
affect one in three Americans born in the year 2000 [1] resulting in annual T2DM-related
costs of $256 billion [2]. Low-income urban and rural areas such as the Appalachian region
bear a disproportionate burden of the national T2DM epidemic [3]. In West Virginia (WV),
the statewide age-adjustment prevalence of diagnosed T2DM is 10.4% [4] while the average
prevalence rate of T2DM in rural Appalachian Ohio (OH) counties is 11.3% [5] exceeding
the national average of 9.3% [1].The Appalachian region also bears a disproportionate
burden of major depressive disorder (MDD; 8.2%) compared to non-Appalachian areas
(7.6%), with higher rates found in central Appalachian states (10.6%) such as WV and OH
than northern or southern states [6].
Barriers to care for T2DM and MDD in low-income urban and rural areas such as central
Appalachia are considerable and similar. Decreased access to health and mental health care
providers, lack of public transportation and rising costs for private transportation (e.g. gas
prices) in the context of geographic isolation pose significant barriers to consistent and
effective health and mental health care [7–8]. Patients with T2DM have been found to be
two times more likely to experience depressive symptoms than their non-diabetic peers with
one in four patients reporting clinically significant depressive symptoms and 11.4% meeting
criteria for MDD [9].
Depressive symptoms have been shown to be associated with worsened blood glucose levels
[10] and T2DM complications [11]. In addition, significant functional and financial costs are
associated with depression and T2DM including decreased adherence to diabetes care
regimens[12], increased functional disability [13], increased health care costs without
resulting improvements in depression or diabetes outcomes [14], decreased quality of life
[15–16]and earlier mortality attributable to all causes (17–18).
Few controlled treatment trials have been conducted to treat depression and T2DM [19–23].
Only three have evaluated behavioral treatment strategies in this population. In a meta-
analysis of 29 randomized controlled trials evaluating cognitive behavioral therapy (CBT)
treatment for MDD across a continuum of disease states, a robust effect size (−.83)
documented the efficacy of this approach [24]. In a study of 51 patients
(meanage53+10years;60%female)diagnosedwithT2DM(meanduration 8 years) and MDD
randomly assigned to a 10-week individualized CBT or control condition without
medication intervention, Lustman found that patients receiving CBT were 3 times more
likely to experience depression remission at post-treatment assessment than controls [19].
Although no group differences in A1c levels were found at post-treatment assessment
(adjusted for baseline values), patients in the CBT condition showed improvement in A1c at
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the 6-month follow-up assessment compared to controls [19]. Treatment responsiveness
appeared to be associated with severity of depression and A1c at baseline [19,25].
In the Pathways Study, problem-solving therapy (a variation of CBT) was integrated within
the primary care setting to treat depression in adults with T2DM [23]. Participants
randomized to a stepped-care problem-solving therapy intervention reported higher levels of
treatment exposure, satisfaction with care and improved depression outcomes compared to
patients in the usual care group. In this study, improvements in glycemic control were not
observed immediately following care or at 6- or 12-month follow-up assessments [23].Taken
together; these studies demonstrate the efficacy of CBT in treating depression in adults with
T2DMwith mixed results associated with changes in glycemic control.
Exercise has the potential to directly improve glycemic outcomes in the context of MDD
treatment and has been shown to be an efficacious treatment for clinical depression among
adults without T2DM [26–27]. In a meta-analysis of 37 exercise intervention trials in
clinically depressed samples, Craft & Landers [28]found a large overall effect size (−.72) in
the reduction of clinical depression with the greatest impact found in samples with
moderate-to-severe levels of depression. Exercise interventions of 9 to12 weeks showed
significantly greater impact on depression outcomes, but no differences were observed in the
types of exercise used in treatment protocols. Exercise interventions have also been shown to
improve glycemic control in patients with T2DM [29–34].
To date, only one randomized controlled trial (RCT) has examined the impact of exercise on
depression in adults with type 2 diabetes. Piette and colleagues randomized 291 adult
patients with T2DM and depressive symptoms (mild to severe) to 12 weeks of manualized
telephone-based CBT (with 9 monthly booster sessions) with a walking programor enhanced
UC [35]. At 12-month follow-up, 58% of participants in the intervention group had
depressive symptoms fall below the mild threshold. Number of steps was higher and systolic
blood pressure was lower in the intervention group at follow-up. No changes were observed
in A1c at the 12-month follow-up assessment [35]. The telephone-based CBT and walking
interventions were combined and could not be evaluated for depression and A1c outcomes
separately.
To date, the existing literature has utilized traditional randomized controlled trials that make
use of research or health care personnel to implement the interventions. No studies have
evaluated the comparative effectiveness of CBT and exercise by implementing these
interventions with community fitness and mental health providers using a community-
engaged research (CEnR) approach. The challenge for health care providers and
communities is to create depression treatment programs for T2DM patients that will reach
the largest number of people at the lowest possible cost and burden to health care
organizations. Program ACTIVE II has been designed to create a model program of
community-based depression treatment using a CEnR design that may be disseminated and
adopted nationally. Central to this model is the assumption that effective depression
treatment requires multiple avenues of access beyond the formal health care system and
multiple approaches to depression treatment such as CBT and exercise. Program ACTIVE II
has been designed to simultaneously achieve two overarching goals: 1) to test the
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comparative effectiveness of the cognitive behavioral therapy (CBT) and community-based
exercise (EXER) to usual care (UC); and 2) to develop a sustainable program that may be
used as a scalable model for T2DM and depression treatment for national dissemination.
The research team has partnered with community mental health providers and exercise
facilities to implement the intervention. This paper reports on the innovative design and
methodology of this large-scale multi-site trial.
Research Design and Methods
Program ACTIVE II is a 2-by-2 factorial repeated measures RCT design. The study is a
multi-center trial in 3 states designed to maximize generalizability of the findings across
high risk groups in both urban and rural areas to assess outcomes and to build the
infrastructure necessary to achieve a sustainable program. Program ACTIVE II uses a
community-engaged research (CEnR) approach in which community organizations are
engaged in all aspects of the study: recruitment, intervention implementation, and
dissemination of findings. This approach confers additional validity to the study outcomes
by examining the effectiveness of the intervention in the sites where they are ultimately
designed to take place and demonstrated stakeholder commitment to the intervention which
serves as a foundation for the ultimate adoption of the Program ACTIVE intervention
beyond the period of federal funding.
The purpose of Program ACTIVE II is to address two primary aims: 1) to compare changes
in glycemic control across individual intervention groups to usual care (UC) at post-
intervention (POST) and 6- and 12-month follow-up assessments; and 2) to compare
changes in MDD outcomes across individual intervention groups to UCat POST and 6- and
12-month follow-up assessments. The study will also address two secondary aims: 1) to
compare changes in cardiovascular risk factors (e.g. LDL cholesterol) across individual
groups to UC at each of the 3 time points; and 2) to calculate the cost-effectiveness of each
treatment arm in terms of predicted incidence of cardiovascular complications over a 10-year
period.
Sample size
Based on our pilot study [36] and a meta-analysis by Boule et al., we used a conservative
assumption of a mean (SD) difference of 0.6% (1.4%) in improving A1c between the UC
and exercise groups at post intervention [29].Using a sample size of 43 in each of the four
treatment groups will have 80% power to detect the main effect of exercise. However, we
will recruit 54 per group assuming a 20% dropout rate.
In estimating the sample size to detect changes in MDD outcomes, we assumed 60% and
30% remission rates for the CBT and UC groups, respectively, at post intervention [19].
Using a sample size of 43 in each of the four treatment groups will have 97% power to
detect the main effect of CBT.
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Randomization
A site-specific computer generated randomization list was used to randomly assign study
subjects to one of the four treatment groups. A block size of four was used to ensure balance
in number of subjects recruited in four groups after recruiting every four subjects.
Characteristics
Inclusion/Exclusion Criteria—Inclusion criteria: age 18 or older, ambulatory status,
diagnosis of T2DM for one year duration or longer, major depression lasting 2 weeks or
longer with no evidence of psychotic symptoms. Medical exclusion criteria include: history
of diabetic ketoacidosis (DKA), continuous insulin therapy since T2DM diagnosis, stage 2
hypertension as defined by JNC VII, recent cardiac events (e.g. unstable angina, diagnosed
angina, PTCA, any cardiac intervention for CAD or tachydysrhythmias in the past 6
months), laser surgery for proliferative retinopathy in the past 6 months, history of stroke,
lower limb amputation, asensory peripheral neuropathy, aortic stenosis or other severe
valvular heart disease, atrial fibrillation, severe COPD (e.g., basal oxygen), class III or IV
heart failure or medical instability. Psychiatric exclusion criteria include: active suicidal
ideation or a history of suicide attempt, bipolar depression or history of psychotic disorder
and current substance abuse or dependence disorder. Participants who are currently
prescribed antidepressant medications for 6 weeks or longer and who meet diagnostic
criteria for major depression without psychotic features are included.
Participants who report the use of a current antidepressant medication for 5 weeks or less are
excluded or deferred for later screening after the 6-week period. Participants who are
currently receiving psychotherapy from a mental health provider for MDD are excluded.
Participants who are currently receiving only medication management from a psychiatrist
are included. Respondents who meet eligibility criteria are invited to participate in the
baseline screening assessment and referred to their local site PI.
Recruitment
Participants are recruited from communities served by the 3 intervention areas: Indianapolis,
southeastern Ohio/western West Virginia and north central West Virginia. Advertising takes
place via physician offices, newspapers, radio stations, community centers, partnering
community organizations and community events. In addition, patients of partner medical
practices are contacted by phone to receive information about the study and to inquire about
interest and eligibility (IU and WV). The recruitment flow chart is shown in Figure 1
(below).Individuals are screened by telephone by trained study staff to determine initial
eligibility. Once eligible via phone screen, participants are scheduled for a baseline
assessment visit where the informed consent takes place. Medical and psychiatric data from
the baseline assessment are reviewed by the study or site medical directors (JS. FS, KF,
KM), exercise physiologist (GH) and PI (MdG) as a group to determine eligibility for study
enrollment. Eligible participants are then randomly assigned to one of the four groups: CBT,
EXER, CBT+EXER or UC.
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Assessment procedures
Psychological, behavioral and physiologic measures are administered at each assessment
period: baseline, post-intervention, 6- and 12-month follow-up with the exception of
demographic characteristics (baseline only). Measures are shown in Table 1.
At the beginning of the baseline assessment visit, individuals are consented to participate in
the study by the Site PI or project coordinator. Baseline assessment includes the medical
history interview, blood draws, anthropometric measurements and fitness assessment.
Participants are given a pedometer, food and activity diaries and questionnaires to complete
following the baseline assessment. Participants complete psychosocial measures at home
(returned by mail) and complete a SCID Axis I interview by phone. The core investigator
team, site PIs and project coordinators conduct weekly teleconferences to review all data
following baseline assessment. Participants who meet all study criteria are randomized to
one of the four intervention groups, scheduled for a free nutritional education program and
their first intervention session (CBT, EXER or CBT+EXER) the following week.
Interventions
The active interventions in Program ACTIVE II are 12-weeks of community-based exercise
and 10 individual sessions of CBT. In order to facilitate diabetes education and to offer an
incentive to UC participants,
Dining with Diabetes
nutrition classes are provided to
participants in all arms. Based on prior studies, nutrition education is not expected to
influence depression outcomes [19].
CBT Intervention—CBT has gained wide acceptance as an efficacious intervention
approach for the treatment of depression [50]. CBT posits that cognitions, emotions and
behaviors are interwoven and mutually reinforcing in the depressed patient [50]. Treatment
involves the identification and reframing of “automatic thoughts” (i.e., cognitive biases) that
work in the service of depressogenic core cognitive beliefs [50]. Cognitive biases and core
beliefs are empirically tested and restructured. Behavioral techniques, such as increasing
daily activity and development and interaction with social support networks are interwoven
into CBT therapy [50]. The use of cognitive and behavioral tools modeled in therapy and
generalized by the participant through take home activities provides participants with an
opportunity to generalize skills to situations beyond the therapeutic relationship.
CBT sessions are conducted by trained licensed mental health providers currently in practice
in their respective communities. They represent the range of practice environments from
individual private practitioners to community mental health centers. Participants receive 10
sessions of CBT using the manualized approach based on Beck’s model of cognitive therapy
[50].Sessions are scheduled weekly over the course of the 12-week period. In light of the
large array of skills that are possible to include in the CBT framework, selected goals have
been targeted for our brief therapy format (presentation of CBT model; thought records,
cognitive distortions, counterarguments, cognitive reframing, automatic thoughts, core
beliefs, and relapse prevention). CBT therapists receive training in CBT and manualized
training approach from the study team.
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Exercise Intervention—The exercise protocol is a community-based exercise
intervention based on the aerobic exercise goals adapted from the Lifestyle Balance behavior
arm of the DPP [44]. Partner exercise facilities represent a range of fitness facilities
including physical therapy practices, community centers and for-profit and non-profit fitness
organizations (e.g. YMCA). Trained instructors at each facility provide 6 classes of
monitored instruction on exercise to participants to meet heart rate and activity-level goals.
Membership to the centers is provided to participants free of cost throughout the 12-week
intervention period. Passes to fitness facilities and costs for time spent with the fitness
trainer are purchased by the grant to increase access to exercise for the duration of the
protocol. These costs replicate costs of the program to community members of an
independent program.
Exercise goals are adapted to accommodate the physical and medical restrictions of an
older-adult T2DM population. Exercise prescriptions are based on the results obtained from
the baseline 6MWT. Participants are given exercise goals of performing 150 minutes per
week of moderate activity at 40- <60% of heart rate reserve (HRR), comparable to a Rating
of Perceived Exertion of 11–13. These goals may be modified based on results of the 6
Minute Walk Test (6MWT). Due to high rates of sedentary behaviors in this population,
physical activity goals are increased in a graduated fashion during Weeks 1–3, beginning
with 100 minutes of weekly aerobic exercise to 150 minutes of total aerobic weekly exercise
by Weeks 4–12 [47]. Intensity of activity begins at 40% in Week 1 and progresses as
tolerated, but continues to remain below 60% of HRR.
In order to provide participants with the necessary training to begin a safe exercise program,
exercise classes are taught by trained fitness instructors at each exercise site in Weeks 1–4
and again in Weeks 6 and 8. In Week 1, participants are introduced to the proper use of
exercise equipment and the exercise prescriptions. During these sessions, participants are
monitored for 50-minutes of exercise by the exercise fitness instructor. Participants are
trained to exercise in a manner consistent with ACSM recommendations including 10
minutes of pre-activity (warm-up and stretching), 30 minutes of active exercise (endurance),
and 10 minutes of post-activity (cool down, recovery) [47,51]. Participants receive feedback
throughout the 50-minute session on their intensity for each given activity. Heart rate and
blood pressure are measured at rest, at peak activity level, and following recovery.
Participants are trained to utilize the Borg Scale [52] during their activity to monitor exercise
intensity.
In Weeks 2–4, participants are given personalized instruction on exercise modes available
including walking on a track, use of treadmills and stationary recumbent/upright ergometers
consistent with the equipment of each fitness location. In weeks 6 and 8, participants attend
an in-person booster session at their local exercise center to re-establish the appropriate
exercise intensity and assess exercise technique. Exercise prescriptions may be adjusted at
this time based on the information obtained about exercise intensity. At each class, a chapter
from the Program ACTIVE II Exercise Manual is provided to participants. Adapted from the
DPP Lifestyle Balance intervention materials, the manual is designed to address
psychological barriers associated with physical activity (e.g. social support, motivation,
behavioral goals).
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Participants are asked to complete weekly exercise diaries and to record number of steps
measured using pedometers provided by the study (Weeks 1–12) on paper or in electronic
form through the website. Participants are contacted bi-weekly by a member of the study
team to review information from activity diaries and pedometers and to evaluate any
exercise-related medical concerns including: hyperglycemia, hypoglycemia, joint pain, back
pain, angina, lightheadedness, and symptoms of hypotension. Data from participants who
report medical symptoms resulting from exercise will be shared with the Medical Director
for the respective site. The development of severe adverse events is communicated to the site
Medical Director, Data Safety and Monitoring Panel and hosting IRB offices for
consultation. SMBG data is downloaded electronically to examine significant changes in
daily blood sugars as a result of exercise. Participants who show increased instances of
hyper- or hypoglycemia are contacted by the project coordinator and advised to contact their
primary care provider for assessment of medications. Participants are provided with
electronic (via website) and paper (as needed) supplemental adherence materials (i.e. toolkit)
such as walking maps, self-care information, and games to promote adherence.
Nutrition Intervention—In order to evaluate the effectiveness of the target interventions
in the context of T2DM treatment best practices, participants in all 4 groups are provided
classes in the Dining with Diabetes (DWD) program through The Ohio State University,
West Virginia University Extension or Purdue University Marion County Extension.
Statistical analyses
The intention-to-treat principle will be used for all analyses. Differences in participants’
baseline characteristics among 4 groups will be evaluated by ANOVA or the nonparametric
Kruskal-Wallis test for continuous outcomes and by Chi-square test for categorical
outcomes. A mixed-model analysis of variance including site, treatment group, time, gender,
race, age, baseline value of A1c will be used to assess the effects of exercise on A1c at post-
intervention, 6- and 12-month. Participants will be treated as a random effect and a un-
structure covariance matrix will be used. The dichotomous primary outcome, remission in
depression, will be analyzed by a non-linear mixed-effects model and will adjust for
potential confounder’s gender, race, age and baseline depression score. In each of the above
two models, an interaction effect between time and treatment group will be assessed first. If
there is no interaction effect, the overall treatment difference will be assessed. Otherwise,
treatment difference will be assessed at each time point. The model will be fitted by the SAS
procedure NLMIXED.
Secondary Outcomes
Functional exercise status and cardiovascular risk factors
A repeated measures ANCOVA will be conducted to assess changes in highest HR during
the 6 minute walk test, distance achieved, LDL-C, HDL-C, triglycerides, and resting blood
pressure from baseline to POST and baseline to the 6- and 12-month assessments.
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Cost-effectiveness (CE) analyses
A Markov decision model of type 2 diabetes progression to complications will be
constructed using cost data collected at baseline, post-intervention, 6 and 12 months of
follow-up. Short- and long-term effects of the intervention can be estimated by including
time horizons 3, 10, 20 and lifetime in the Markov model. All costs will be adjusted to the
year 2007 using the US Consumer Price Index.
Markov models
We will develop a Markov decision model with sensitivity analyses to estimate the
Incremental Cost-Effectiveness ratio (ICER) of the intervention compared to UC as
implemented in Program ACTIVE II. An ICER is computed by the ratio of ΔC/ΔE where
ΔC represents the change in cost due to the intervention compared with UC and ΔE
represents the change in health benefits due to the intervention compared with UC. We will
use TreeAge Pro Suite 2009 software (TreeAge Software, Williamstown, MA). The model
will directly incorporate intervention effectiveness and cost data as well as event
probabilities from the RCT to estimate life expectancy, quality-adjusted life-expectancy
(expressed as QALYs), clinical outcomes (diabetes complications), and direct medical and
nonmedical costs associated with the interventions and UC.
Data Safety and Monitoring Panel
A Data Safety and Monitoring Panel (DSMP) were created to provide expert consultation in
the primary disciplines involved in the content of the study: psychology, medicine, and
exercise physiology. These consultants provide input on issues such as metabolic or
physiological changes in participants during participation, mental status of participants, and
implementation of the exercise protocol throughout Program ACTIVE II. Members of the
panel are available for consultation for issues of research ethics, clinical care, and human
subject’s protection. Members of the panel are independent from the research team to ensure
objectivity in the treatment of participants.
Data integrity is reviewed by the Core Investigators in consultation with Dr. Chandan Saha
of the IUSM Department of Biostatistics. The Core Investigators meet monthly by phone to
discuss issues related to recruitment, implementation of the intervention, participant safety,
and to monitor data trends (e.g., adherence, missing data.
Conclusions
T2DM and co-morbid depression represents a growing challenge to patients and health care
systems as the prevalence of both disorders rises but access to treatment remains limited. In
this study, we are investigating the comparative effectiveness of a combination of CBT and
exercise using a CErN approach in which community fitness and mental health partners
provide depression treatment to study participants. This approach is novel because it is the
first study to examine the comparative effectiveness of two behavioral treatment approaches
to depression and T2DM. Moreover, it leverages community resources such as fitness
centers, community centers and community mental health professionals that already exist in
rural and low-income urban communities to serve as treatment partners to health care
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centers. At the same time, it expands knowledge of diabetes treatment issues to these
community providers thereby expanding continuity of care for participants.
Data from this study will provide the empirical foundation for community stakeholders to
evaluate the value of this program in terms of health and mental health outcomes in their
communities and to identify the ways that this may become a sustainable treatment resource
for communities beyond the period of federal funding. Lessons learned from this study will
also inform the dissemination of this intervention as a model that may be scaled to the
national level to alleviate the burden and costs with this important set of disorders.
Supplementary Material
Refer to Web version on PubMed Central for supplementary material.
Acknowledgments
Program ACTIVE II was funded by the National Institute of Diabetes, Digestive Disease & Kidneys
(R18DK092765 & R34DK071545). The Program ACTIVE Research Team wishes to thank the following
individuals for their many contributions to this study: Barb Myers, B.S., CCRP; Rachel Clift, RN; Susan Eason,
M.A.; David Donley, M.S.; Lindsey Sams, B.S.; Jaclyn Babe, B.S.; Christiaan Abildso, Ph.D; Daniel Bonner, M.S.,
Melinda Ruberg, B.S.; Bernadette Heckman, Ph.D.; CammieStarner; Lynn Petrik; Tracey Garrett; Chelsea Holbert,
M.A.; Debby Wimer; Kelly Chaudoin, M.A.; Sarah Mielens, M.A.; Ellen Knapp, M.A.; Kent Crick, B.S.; Danielle
Epler, M.S.; Michelle Weinstein, M.S.; Kasey Goodpaster, Ph.D.; Brett McKinney; KishaWilkerson.
We also wish to acknowledge our community partners who delivered interventions to our participants: Hopewell
Health Center, Belpre and Athens, OH; Marietta Family YMCA, Marietta, OH; Sharon Sheets, Athens, OH; Jason
Weber, Athens, OH; Sheila Williams, Athens, OH; Counseling & Wellness Center, Parkersburg, WV; Mountain
River Physical Therapy, Parkersburg and Vienna, WV; Family Fitness, Parkersburg, WV; Wellworks, Athens, OH;
Athens Community Center, Athens, OH; West Virginia University County Extension Program; The Ohio State
University Washington County Extension Program; Purdue University Marion County Extension Program; United
Summit Center, Clarksburg, WV;., Kimberly Yingling, M.A., NCC, LPC, Morgantown, WV; Tygart Valley
Rehabilitation and Fitness Center, Grafton, WV; Fairmont General HealthPlus, Fairmont, WV; Pro Performance,
Morgantown, WV; Rob’s Fitness Factory, Morgantown, WV;, Harrison County YMCA, Lodgeville Branch,
Bridgeport, WV; Midtown Community Mental Health, Indianapolis, IN; YMCA of Greater Indianapolis,
Indianapolis, IN; Physically Active Residential Communities and Schools (PARCS) Program, Indianapolis, IN;
Chase Near Eastside Legacy Center, Indianapolis, IN; Natalie Johann; Denise Sayasit; Evan Heald; Latisha
Idlewine; Julie Kenny; Matt Larson; Gary Brown; Chelsy Winters; Anne Graves; Christina Ferroli; Lydia
Armstrong; LaRona Dixon; Allison Plopper; Ben Jones; James Brummett; Kathi Bledsoe; Allison White; Ella
Vinvi; Cynthia Donel; Monica Staples; Tina Wiesert; Carol Hendricks; Cindy Wilson; Richard Nulter; Kim
Johnson, M.A.; Adryanne Garrett; Bonnie de Lange; Cassandra Watt; Priscilla Leavitt, Ph.D.; Rick Stanley, Ph.D.;
Stephen Givens, Psy.D.; Sharon Sheets, M.A.; Suzy Zumwalde; Dave Vogel; Noah Albrecht; Joe Leaman; Erin
Weber; Allison Burner; Dan Braatz; CassyOffenberger; Eric Weber; Jonathan Rodriquez; Pat Perine; Louie Haer;
Josh Christen; McKenzie Walter; Flynt Smathers; Rich Campitelli; Kathy Dodrill; Brian Sharp, Ph.D.; Dana
Nugent, Psy.D; Mark Tipton, M.A., A.A.D.C, LPC; Eric Shaw, M.P.T; Rick Williams, C.D.M., M.P.F.T; Shane
Trivigno, B.S.; Kellie Snyder, B.S., M.B.A, C.P.T; Beth Burleson, B.S. C.P.T; Brad Wright, B.S, C.P.T; Rob Cress
M.S., C.S.C.S; Jesse Halldin, B.A, CPT; Whitney Hickman, B.S., A.C.S.M; Karen Newton, B.A; Eric Murphy,
M.S, M.A; Jennifer Murray, M.S; Lauren Prinzo, M.P.A; Rebecca Smith, M.B.A.
We thank all of the participants of Program ACTIVE who gave generously of their time and energy to engage in a
new research activity. We are grateful for their generosity of spirit and their willingness to try something new.
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Figure 1.
Recruitment Flow Chart
Separate randomization lists were generated by the study statistician for use by each study
site.
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Author Manuscript Author Manuscript Author Manuscript Author Manuscript
de Groot et al. Page 15
Table 1
Administration of Assessment Measures in Program ACTIVE
Measures Screening Baseline POST 6- and 12- Mo.
Follow-Up Outcome Variable Covariate Clinical Monitoring Variable
Psychosocial
Demographic Characteristics XX
Structured Clinical Interview for the DSM-IVTR (SCID Axis
I Disorders) X (Screener) X X X Primary
Lifetime Current Current
Beck Depression Inventory (BDI) X X X Primary
Diabetes Quality of Life (DQOL) X X X Secondary
SF-36 Quality of Life Measure X X X Secondary
Chronic Illness Resource Survey (CIRS) X X X Secondary
Behavioral
Physical Activity Diary (1 week) X X X X
Pedometer (1 week) X X X X
Physiologic
Glycated Hemoglobin (A1c) X X X Primary
Blood lipid profile (HDL-C; triglycerides) X X X Secondary
Self-Monitored Blood Glucose (SMBG) X X X X
Medical History Interview X X
Medical Status Review X X X
6-Minute Walk Test X X X Secondary
Height X X X X
Weight X X X X
Waist/Hip Girth X X X
Blood Pressure X X X Secondary X
Resting Heart Rate/Pulse X X X X
Perceived Exertion (Borg rating) X X X X
J Diabetes Res Ther
. Author manuscript; available in PMC 2016 August 04.

Supplementary resource (1)

... The study design is described in detail elsewhere (14). Participants were screened by telephone and invited to attend a baseline assessment visit during which inclusion and exclusion criteria were further evaluated (see MEASURES below). ...
... Inclusion and exclusion criteria are shown in Supplementary Table 1. Respondents who met eligibility criteria were invited to participate in the baseline screening assessment and referred to their local study site (14). ...
... Advertising was conducted in physician offices, newspapers, radio stations, community centers, partnering community organizations, and community events. Patients of partner medical practices were contacted by phone for recruitment to the study by research staff (14). Participants were recruited from May 2012 to May 2016. ...
Article
Objective: Depression (major depressive disorder [MDD]) in adults with type 2 diabetes mellitus (T2DM) is associated with worsened diabetes complications, increased health care costs, and early mortality. Program ACTIVE II was a randomized, controlled, multicenter treatment trial designed to test the comparative effectiveness of cognitive behavioral therapy (CBT) and/or community-based exercise (EXER) on diabetes and depression outcomes compared with usual care (UC). Research design and methods: Using a 2 × 2 factorial randomized controlled trial design, adults with T2DM for ≥1 year who met DSM-IV-TR criteria for MDD were randomized to CBT (10 sessions occurring over 12 weeks; N = 36), EXER (12 weeks of community-based exercise including six sessions with a personal trainer; N = 34), CBT+EXER (concurrent over a 12-week period; N = 34), and UC (N = 36). Primary outcomes were depression remission rate (assessed by psychiatric interviewers blind to assignment) and change in glycemic control (HbA1c). Results: The mean age was 56.0 years (SD 10.7). Participants were female (77%), white (71%), and married (52%). After controlling for education and antidepressant use, odds of achieving full MDD remission in the intervention groups were 5.0-6.8 times greater than UC (P < 0.0167). The CBT+EXER group demonstrated improved HbA1c compared with UC. For participants with a baseline HbA1c ≥7.0%, exploratory post hoc subgroup analysis showed that the CBT+EXER group had a 1.1% improvement in HbA1c (P < 0.0001) after controlling for covariates. Conclusions: The Program ACTIVE behavioral treatment interventions demonstrated clinically meaningful improvements in depression outcomes in adults with T2DM and MDD. These community-based interventions are complementary to medical care and extend access to those in rural and urban areas.
... Program ACTIVE (Adults Coming Together to Increase Vital Exercise) II was a multicenter repeated-measures randomized controlled trial conducted in three U.S. states including Ohio, West Virginia, and Indiana (21,22). The study used a community-engaged research approach in which community organizations participated in recruitment, intervention implementation, and dissemination of findings. ...
... The study protocol was approved by the institutional review boards of Indiana University, Ohio University, and West Virginia University. The study design and outcomes have previously been published (21)(22)(23). Overall, Program ACTIVE II (22) demonstrated that compared with usual care (UC), the community-based exercise (EXER), and CBT interventions delivered individually (EXER alone or CBT alone) and concurrently (EXER1CBT) resulted in significant improvements in depression, diabetes distress, or cardiometabolic outcomes among rural and urban adults with type 2 diabetes and MDD. ...
Article
Full-text available
Objective: We estimated the cost-effectiveness of the Program ACTIVE (Adults Coming Together to Increase Vital Exercise) II community-based exercise (EXER), cognitive behavioral therapy (CBT), and EXER+CBT interventions in adults with type 2 diabetes and depression relative to usual care (UC) and each other. Research design and methods: Data were integrated into the Michigan Model for Diabetes to estimate cost and health outcomes over a 10-year simulation time horizon from the health care sector and societal perspectives, discounting costs and benefits at 3% annually. Primary outcome was cost per quality-adjusted life-year (QALY) gained. Results: From the health care sector perspective, the EXER intervention strategy saved 313(USD)perpatientandproduced0.38moreQALY(costsaving),theCBTinterventionstrategycost313 (USD) per patient and produced 0.38 more QALY (cost saving), the CBT intervention strategy cost 596 more and gained 0.29 more QALY (2,058/QALY),andtheEXER+CBTinterventionstrategycost2,058/QALY), and the EXER+CBT intervention strategy cost 403 more and gained 0.69 more QALY (585/QALY)comparedwithUC.BothEXERandEXER+CBTinterventionsdominatedtheCBTintervention.ComparedwithEXER,theEXER+CBTinterventionstrategycost585/QALY) compared with UC. Both EXER and EXER+CBT interventions dominated the CBT intervention. Compared with EXER, the EXER+CBT intervention strategy cost 716 more and gained 0.31 more QALY (2,323/QALY).Fromthesocietalperspective,comparedwithUC,theEXERinterventionstrategysaved2,323/QALY). From the societal perspective, compared with UC, the EXER intervention strategy saved 126 (cost saving), the CBT intervention strategy cost 2,838/QALY,andtheEXER+CBTinterventionstrategycost2,838/QALY, and the EXER+CBT intervention strategy cost 1,167/QALY. Both EXER and EXER+CBT interventions still dominated the CBT intervention. In comparison with EXER, the EXER+CBT intervention strategy cost $3,021/QALY. Results were robust in sensitivity analyses. Conclusions: All three Program ACTIVE II interventions represented a good value for money compared with UC. The EXER+CBT intervention was highly cost-effective or cost saving compared with the CBT or EXER interventions.
... Because depressive symptoms were measured continuously, the odds ratio indicates that the odds of having diabetes increased by 5% for every 1-point increase in PHQ-9 score above the mean. Odds ratios were significant for all covariates except the "other" level of ethnicity, indicating protective effects for being female, being Caucasian, being younger (closer to age 40), and having at least some postsecondary education. For every year of age over the mean, the odds of having diabetes increased by 5% ...
... This model can then be used to develop interventions that will treat both body and mind. For example, several randomized controlled trials are underway in which researchers are using cognitive behavioral therapy to relieve depression among people living with diabetes, with the ultimate goal of managing their diabetes more effectively [40,41]. ...
Article
Full-text available
Background Empirical research has revealed a positive relationship between type 2 diabetes mellitus and depression, but questions remain regarding timing of depression measurement, types of instruments used to measure depression, and whether “depression” is defined as clinical depression or depressive symptoms. The present study sought to establish the robustness of the depression-diabetes relationship across depression definition, severity of depressive symptoms, recent depression, and lifetime depression in a nationally representative dataset and a large rural dataset. Methods The present examination, conducted between 2014 and 2015, used two large secondary datasets: the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2008 (n = 3072) and the Arthritis, Coping, and Emotion Study (ACES) from 2002 to 2006 (n = 2300). Depressive symptoms in NHANES were measured using the Patient Health Questionnaire 9-item survey (PHQ-9). ACES used the Center for Epidemiologic Studies—Depression Scale (CES-D) to measure depressive symptoms and the Composite International Diagnostic Interview (CIDI) to measure diagnosable depression. Diabetes was modelled as the dichotomous outcome variable (presence vs. absence of diabetes). Logistic regression was used for all analyses, most of which were cross-sectional. Analyses controlled for age, ethnicity, sex, education, and body mass index, and NHANES analyses used sample weights to account for the complex survey design. Additional analyses using NHANES data focused on the addition of health behavior variables and inflammation to the model. Results NHANES. Every one-point increase in depressive symptoms was associated with a 5% increase in odds of having diabetes [OR: 1.05 (CI: 1.03, 1.07)]. These findings persisted after controlling for health behaviors and inflammation. ACES. For every one-point increase in depressive symptom score, odds of having diabetes increased by 2% [OR: 1.02 (CI: 1.01, 1.03)]. Recent (past 12 months) depression [OR: 1.49, (CI: 1.03, 2.13)] and lifetime depression [OR: 1.40 (CI: 1.09, 1.81)] were also significantly associated with having diabetes. Conclusions This study provides evidence for the robustness of the relationship between depression or depressive symptoms and diabetes and demonstrates that depression occurring over the lifetime can be associated with diabetes just as robustly as that which occurs more proximal to the time of study measurement.
... Numerous studies suggest a bidirectional relationship between diabetes and depression 2 , with individuals with diabetes being 2-3 times more likely to develop depression than the general population. Conversely, depression increases the risk of developing type 2 diabetes by approximately 60% 3 . The comorbidity of depression and diabetes can impair self-management and reduce treatment adherence, potentially exacerbating each other and thereby increasing healthcare costs and placing a substantial burden on families and society 4 . ...
Article
Full-text available
Depression impairs self-management in diabetic patients, exacerbates insulin resistance, and elevates glycated hemoglobin (HbA1c) levels, thereby increasing diabetes risk. This study analyzed data from 30,386 participants in the National Health and Nutrition Examination Survey (NHANES), assessing depression severity using the 9-item Patient Health Questionnaire (PHQ-9) and evaluating diabetes status through clinical markers such as HbA1c, random blood glucose, and fasting blood glucose. Participants were stratified by depression severity and diabetes status to examine the relationship between depression and diabetes risk. We applied descriptive statistics, logistic regression models, subgroup analyses, and restricted cubic spline (RCS) modeling to explore this association. The results revealed that greater depression severity was significantly associated with increased diabetes incidence, elevated HbA1c, fasting glucose, and insulin levels. Multivariate regression analysis confirmed a consistent positive correlation between depression severity and diabetes risk. Subgroup analyses further identified significant relationships between depression and various demographic and behavioral factors, including gender, race, BMI, smoking status, and prediabetic conditions. Additionally, the RCS model demonstrated a clear increase in diabetes risk with rising PHQ-9 scores. In conclusion, our study demonstrates that the severity of depression is positively correlated with the risk of diabetes, and this association may be closely linked to various glycemic and lipid metabolic parameters.
... Details of the study design and eligibility criteria have been detailed elsewhere. (15) Recruitment Approach Participants were recruited from rural southeastern Ohio (OH), north-central West Virginia (WV), and central Indiana (IN) communities. To ensure that recruitment goals were met, the study utilized multiple recruitments approaches, continually assessing the effectiveness of each, and adjusting strategies as necessary.(16) ...
Preprint
Full-text available
Background Participant recruitment for clinical trials is a significant challenge for the scientific research community. Federal funding agencies have made continuation of funding of clinical trials contingent on meeting recruitment targets. It is incumbent on investigators to carefully set study recruitment timelines and resource needs to meet those goals as required under current funding mechanisms. This paper highlights the cost, labor, and barriers to recruitment for Program ACTVE II, a successful multi-site randomized controlled trial of behavioral treatments for depression in adults with type 2 diabetes, conducted in rural and urban settings in three states. Methods Quantitative and qualitative data on recruitment were gathered from study staff throughout the study recruitment period and were used to calculate costs and effort. The study utilized two main approaches to recruitment: 1.) relying on potential participants to see ads in the community and call a toll-free number, and 2.) direct phone calls to potential participants by study staff. Results Contact was attempted with 18,925 people to obtain the enrolled sample of 140. The cost of recruitment activities during the 4.5-year recruitment period totaled 190,056,anaveragecostof190,056, an average cost of 1,358 per enrolled participant. Qualitative evaluations identified multiple barriers to recruitment. Conclusions Recruitment for Program ACTIVE II exemplifies the magnitude of resources needed to reach recruitment targets in the current era. Continuous evaluation, flexibility, and adaptation are required on the part of investigators, community partners, and funding agencies to successfully reach high risk populations in rural and urban areas.
... Eligible participants were randomized, notified of their randomization group (EX, CBT, EX+CBT, or UC), and assigned to an intervention provider, if relevant. Details of the study design and eligibility criteria have been detailed elsewhere [15]. ...
Article
Full-text available
Background: Participant recruitment for clinical trials is a significant challenge for the scientific research community. Federal funding agencies have made continuation of funding of clinical trials contingent on meeting recruitment targets. It is incumbent on investigators to carefully set study recruitment timelines and resource needs to meet those goals as required under current funding mechanisms. This paper highlights the cost, labor, and barriers to recruitment for Program ACTVE II, a successful multisite randomized controlled trial of behavioral treatments for depression in adults with type 2 diabetes, conducted in rural and urban settings in three states. Methods: Quantitative and qualitative data on recruitment were gathered from study staff throughout the study recruitment period and were used to calculate costs and effort. The study utilized two main approaches to recruitment: (1) relying on potential participants to see ads in the community and call a toll-free number; and (2) direct phone calls to potential participants by study staff. Results: Contact was attempted with 18,925 people to obtain the enrolled sample of 140. The cost of recruitment activities during the 4.5-year recruitment period totaled 190,056,anaveragecostof190,056, an average cost of 1358 per enrolled participant. Qualitative evaluations identified multiple barriers to recruitment. Conclusions: Recruitment for Program ACTIVE II exemplifies the magnitude of resources needed to reach recruitment targets in the current era. Continuous evaluation, flexibility, and adaptation are required on the part of investigators, community partners, and funding agencies to successfully reach high-risk populations in rural and urban areas. Trial registration: ClinicalTrials.gov, NCT03371940 . Registered on 13 December 2017.
... Approximately 10% of patients with T2DM also exhibit depression, and about two out of every five patients with T2DM have alexithymia 12,13 . Thus, there is an increased risk of depression in patients with T2DM. ...
Article
Full-text available
Type 2 diabetes mellitus (T2DM) is closely related to depression; however, the exact molecular mechnisms of this association are unknown. Here, we investigated whether circular RNAs (circRNAs) in the blood are related to the occurrence of depression in patients with T2DM. Fourteen patients with T2DM and depressive symptoms, as assessed by the Self-Rating Depression Scale, were included in this study. Cutoff points of 44 (total coarse points) and 55 (standard score) were used to define depression. The Patient Health Questionnaire 9 was used for common mental disorders, and a score of 5 or more the cutoff for depression. Microarray assays and quantitative real-time reverse transcription polymerase chain reaction showed that 183 hsa-circRNAs were significantly upregulated, whereas 64 were downregulated in the T2DM with depression group (p < 0.05) compared with that in the T2DM group. Differentially expressed hsa-circRNAs could interact with microRNAs to target mRNA expression. KEGG pathway analysis predicted that upregulation of hsa-circRNA_003251, hsa-circRNA_015115, hsa-circRNA_100918, and hsa_circRNA_001520 may participate in the thyroid hormone, Wnt, ErbB, and mitogen-activated protein kinase signalling pathways. We speculate that differentially expressed hsa-circRNAs could help us to clarify the pathogenesis of depression in patients with T2DM and could represent novel molecular targets for clinical diagnosis and therapy.
Article
Full-text available
We investigated how COVID-19 has disrupted the work of health professionals who address behavioral and psychosocial needs of people with diabetes (PWD). English language emails were sent to members of five organizations that address psychosocial aspects of diabetes, inviting them to complete a one-time, anonymous, online survey. On a scale from 1=no problem, to 5=serious problem, respondents reported problems with the healthcare system, their workplaces, technology, and concerns about the PWD with whom they work. Respondents (n=123) were from 27 countries, primarily in Europe and North America. The typical respondent was a woman, aged 31-40 years, who worked in an urban hospital in medicine or psychology/psychotherapy. Most judged that the COVID lockdown in their region was moderate or severe. Over half felt moderate to serious levels of stress/burnout or mental health issues. Most participants reported moderate to severe problems due to the lack of clear public health guidelines, concerns with COVID safety of themselves, PWD, and staff, and a lack of access or knowledge on the part of PWD to use diabetes technology and telemedicine. In addition, most participants reported concerns with the psychosocial functioning of PWD during the pandemic. Overall, the pattern of findings reveals a high level of detrimental impact, some of which may be ameliorated with changes in policy and additional services for both health professionals and the PWD with whom they work. Concerns about PWD during the pandemic must go beyond their medical management and also consider the health professionals who provide them with behavioral and psychosocial support.
Article
Purpose The primary aim of this pilot study was to examine the feasibility of codelivering a mental health intervention with an evidence-based type 2 diabetes (T2DM) boot camp care management program. The preliminary impact of participation on symptom scores for depression and anxiety and A1C was also examined. Methods This was a 12-week, non-randomized pilot intervention conducted with a convenience sample of adults with uncontrolled T2DM and moderate depression and/or anxiety at an urban teaching hospital. Co-management intervention delivery was via in-person and telehealth visits. Participants were assessed at baseline and 90 days. Results Participants (n = 18) were African American, majority female (83%), and age 50.7 ± 13.4 years. Significant improvements in mental health outcomes were demonstrated, as measured by a reduction in Patient Health Questionnaire − 9 scores of 2.4 ± 2.9 ( P = .01) and in Generalized Anxiety Disorder − 7 scores of 2.3 ± 1.9 ( P = .001). The pre-post intervention mean A1C improved by 3.4 ± 2.1 units from 12% ± 1.4% to 8.5% ± 1.7% ( P < .001). Conclusion The data generated in this pilot support the feasibility of delivering a diabetes and mental health co-management intervention using a combination of in-person and telemedicine visits to engage adults with T2DM and coexisting moderate depression and/or anxiety. Further research is warranted.
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