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The effect of ALFALIFE™ in improving metabolic syndrome and in reducing low-grade inflammation

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Abstract

This is the first draft of a protocol for an RCT that is going to take place in North Italy, aimed to assess whether Alfa1Linolenic Acid (ALA) is effective in reducing low-grade inflammation and its associated conditions
Study record 38310
Generated: 18/05/2020 12:54:45
Editorial Status: Under assessment
Title and Additional Identifiers
Submission number
38310
ISRCTN
DOI
Public title
The effect of ALFALIFE™ in improving metabolic syndrome and in reducing low-grade
inflammation
Scientific title
Interventional study to verify if ALFALIFE™ as supplementation of a healthy diet modifies, in
adult patients, the content of Alfa1Linolenic Acid in red blood cells; the circulating levels of
prostanoids related to inflammation, thrombosis, and atherosclerosis; and other risk factors for
metabolic heart diseases
Acronym
H4H-03
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol /serial number
H4H-03
Condition category
Nutritional, Metabolic, Endocrine
Date Applied
18/05/2020
Date Assigned
Last Edited
18/05/2020
Prospective/Retrospective
Overall Trial Status
Ongoing
Recruitment status
Not yet recruiting
Study Information
Study hypothesis
The routine administration of ALFALIFE™ modifies the metabolic profile of adult patients with
metabolic syndrome and/or low-grade inflammation, improving conditions associated with
chronic inflammation and hyperactivity of the immune response. ALFALIFE™ supplementation
provides an improvement in inflammatory marker levels and improves the metabolic profile. It
also offers improvement or prophylaxis of the complications of hyperactivation of the immune
response in viral infections, such as COVID-19, and improvement in overall quality of life.
Ethics approval
Granted
Study design
Multicentre longitudinal double-blind randomized clinical trial
Primary study design
Interventional
Secondary study design
Randomised parallel trial
Trial setting
Hospitals
Trial type
Prevention
Overall trial start date
01/06/2020
Overall trial end date
28/02/2021
Overall trial status override
Reason abandoned (if study stopped)
Condition
Metabolic syndrome, low-grade inflammation
Interventions
Participants will be randomly assigned to receive either ALFALIFE™ supplements or an identical
placebo control. Both arms will be asked to take 6 capsules orally each day (1 at breakfast, 2 at
lunch, and 3 at supper) for 120 days. Both groups will be required to maintain a balanced
hypolipidemic and isocaloric diet. There will be a 15 day washout period following baseline
measures being taken before the intervention begins. Immediately after the intervention, these
measurements will be repeated at 120 days. Following this, there will be a 20 day washout period
after which measurements are taken again at 150 days.
ALFALIFE™ is presented in soft capsules; the placebo contains edible oil and is presented in soft
capsules that appear identical to ALFALIFE™. ALFALIFE™ contains cannabis sativa seed oil,
extracted with mechanical process of cold pressing from dehulled seeds of Cannabis sativa. This
oil has the following characteristics: high bioavailability of essential fatty acids such as α-linolenic
acid (ALA) and linoleic acid, and of other polyunsaturated fatty acids such as γ-linolenic acid and
stearidonic acid.
To assess the intervention, the investigators will measure the inflammatory and metabolic
profiles of the participants, conduct medical examination of the participants, and ask the
participants to complete questionnaires.
Blood samples:
The investigators will collect blood from the participants enrolled in the study and will send the
samples for the measurement of:
1. Metabolic analytes: cholesterol total, LDLc, HDLc triglycerides, Lp (a), glycemia, glycated
hemoglobin, HOMA-IR, HOMA-B, leptin, ghrelin, VCAM, ICAM, endothelin, homocysteine,
fibrinogen, uricemia, PCR-HS, cytokines (13), total lymphocytes, ferritin, GOT, GPT, CPK, and
creatinine
2. Measures of diabetes and prediabetes: insulin-resistance, and the lipidic profile
3. Measures of the general inflammatory response: level of those immunomodulators that are
known to be overexpressed in patients with SARS-CoV-2 infection
The samples will be taken at baseline before the 15 days washout period, and again at the end of
the trial (120 days) and at the end of the following washout (150 days)
The blood samples will be collected according to the following procedure:
Investigators will draw blood with the participant in a sitting position, from an antecubital vein of
the arm, with a vacutainer system, in the absence of stasis, after 11-12 hours of fasting (water
intake is allowed). The patient's name, surname, date of birth, date of sampling will be indicated
on all the test tubes and in a special computer register, after completing the privacy forms for
the entire duration of the study. The blood will be collected with a 10 ml vacutainer, preferably
containing EDTA or heparin, without hemolyzing. the sample will be immediately centrifuged to
separate the plasma. If it is not possible to perform the centrifugation immediately, it will be put
on ice until the moment of centrifugation (15 min at 3000 xg). After centrifugation, 3 aliquots of
700 microliters of plasma will be taken, to be placed in 1.5 ml Eppendorf © tubes. The samples
will then be placed immediately at -80 °C. The samples will then be sent to the reference
laboratories for the assay of the analytes. The same procedures will be repeated at each check,
to allow maximum standardization of the procedure.
Medical examination:
To better assess the general condition and better evaluate the effect of the intervention,
investigators will assess the general conditions of the enrolled participants and the level of
perception of their health status. Investigators will perform a full medical examination before
each blood collection.
Medical examination will be performed according to good medical practice standards. The
examiner will record the findings using a transferable or exportable electronic format. The
examiner will always measure, according to shared standard, systolic pressure, diastolic pressure,
mean heart rate, weight, and height (first check only), abdominal circumference.
At the beginning of the study, the investigator will record the participant's medical history
according to a standard template and will record in a form the findings with a special focus of the
participant's diet. At the end of the study the compliance of the participants in regularly taking
the capsules will be assessed (specifying how many and which dose the subject has skipped).
Investigators will record every diet supplementation and drugs taken by the participants during
the whole trial. Any possible side effects should be reported on the medical records/files.
Questionnaires:
Patients will receive a mid-term questionnaire and a second questionnaire at the end of the trial
to assess the level of acceptance defined as perceived easiness to take the capsules, and the
daily and overall compliance.
The questionnaires administered refer to the food history for adherence to the diet and
evaluation of the pro / anti-inflammatory diet, adherence to the administration of alpha-linolenic
acid, and physical activity.
Investigators will also assess the quality of life (SF 12), the quality and quantity of sleep, and any
nutraceutical and supplements intake.
The questionnaire and the table for the evaluation of the responses and for the evaluation of the
diet composition are presented in the investigator's handbook that will be made available to
every researcher. It will include the following annexes:
1. ANNEX I Questionnaire for patient recruitment
2. ANNEX II-IV 7-day recall questionnaires
3. ANNEX V Diet adherence questionnaire
4. ANNEX VI Physical activity monitoring questionnaire: IPAQ
5. ANNEX VII Capsule tolerance / adherence / intake questionnaire
6. ANNEX VIII Sleep Quality Questionnaire: PSQI
7. ANNEX IX Quality of Life Questionnaire: SF12
8. ANNEX X-XIX Isolipid diets while taking soft capsules
Intermediate questionnaires:
During the activities, short questionnaires will be periodically administered to patients for the
sole purpose of verifying the progress of food, physical behaviors, and other factors to keep
attention to the protocol high.
Intervention Type
Supplement
Phase
Drug name(s)
Primary outcome measure
Improvement in low-grade inflammation measured by cholesterol total, LDLc, HDLc triglycerides,
Lp (a), glycemia, glycated hemoglobin, HOMA-IR, HOMA-B, leptin, ghrelin, VCAM, ICAM,
endothelin, homocysteine, fibrinogen, uricemia, PCR-HS, cytokines (13), total lymphocytes,
ferritin, GOT, GPT, CPK, and creatinine levels from blood samples collected at baseline, 120, and
150 days.
Secondary outcome measures
1. Diabetes and prediabetes risk measured by insulin-resistance and lipid profile levels from
blood samples collected at baseline, 120, and 150 days
2. General health and medical conditions measured through full medical history and examination
at baseline, 120, and 150 days
3. Adverse events and side effects assessed through full medical history and examination,
medical records, and recording of all supplements and drugs taken by participants at baseline,
120, and 150 days
4. Participant quality of life measured using the sleep quality questionnaire (PSQI), and quality of
life questionnaire (SF12) at 60 and 120 days
5. Dietary adherence assessed through the diet adherence questionnaire at 60 and 120 days
6. Physical activity assessed through the 7-day recall questionnaire and physical activity
monitoring questionnaire (IPAQ) at 60 and 120 days
7. Participant tolerance and compliance assessed through the capsule tolerance/adherence/
intake questionnaire at 60 and 120 days
Trial website
Participant information sheet
Eligibility
Participant inclusion criteria
1. Patients with non-optimal ALA intake (<RDA of 0.5%)
2. Adults, able to independently express informed consent
3. Aged 40 to 69 years
4. Patients with Metabolic Syndrome
5. Possible or probable Low-grade inflammation as defined below:
5.1. High sensitivity C-reactive protein (HS-CRP) between 3 and 10 mg/L
5.2. Galmes Genetic Score
5.3. INFLA score (Moli-Sani project)
5.4. Clinical, laboratory and nutritional criteria as per the following conditions:
5.4.1. Kaluza J 2020 nutritional questionnaire
5.4.2. Persistent or relapsing clinical symptoms related to chronic
5.4.3. Presence of frequently associated conditions (metabolic, overweight etc.)
5.4.4. BIA-ACC criteria (4 points) and PPG stress flow
5.4.5. Presence of other inflammatory markers (specific morphological fibrinogen ESR markers)
5.4.6. Previous diagnosis made by a specialist
5.4.7. Chronic or phased NSAID intake (to be discontinued during the trial)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
24
Total final Enrolment
Participant exclusion criteria
1. Familial hyperlipoproteinemia, excluding a possible coexisting hyper-lp(a)emia
2. Diabetes mellitus
3. Currently being treated with drugs (any type) or nutritional supplements (any type) or who are
expected to start treatments during the study period
4. Clinical symptoms or instrumental laboratory parameters such as to suggest the presence of
acute or subacute viral/bacterial infection or other inflammation
5. Require lipid-lowering or antithrombophilic therapy (patients with very high cardiovascular risk
, patients with severe and/or unstable atheromasia, in any vascular district, patients with a
history of angina, thromboembolism, TIA, heart infarction, stroke, etc.)
6. Menopausal, premenopausal and postmenopausal women under treatment or with active
post-menopausal symptoms
7. Secondary metabolic diseases, endocrinopathies, and systemic diseases of any kind 8. Disabled
or functionally limited patients
9. Severe depressive syndromes and/or other psychiatric diagnosis
10. Patients who for any reason cannot follow the periodic checks aimed to assess their diet and
the adherence to the study
11. Previous bulimia/anorexia
12. Recent (within 3 months) strong decrease or increase in weight
13. Weight fluctuations greater than the sum of the analytical and pre-analytical physiological
variability according to gender, age and weight
14. Weight trends on multiple measures constantly increasing or decreasing
15. BMI >30
16. Food restrictions due to food intolerances (unless these are attributable to LGI, with the
exclusion of other causes, lactose, nickel, celiac disease, etc., intolerances) and vegan/vegetarian
diets or for any other reason
Recruitment start date
01/07/2020
Recruitment end date
31/07/2020
Recruitment status override
Locations
Countries of recruitment
Italy
Trial participating centres
Trial Centre
Trial Centre Name
Università degli Studi dell'Insubria
Address
Via Ravasi, 2
City
Varese
Country
Italy
Zip
21100
Plain English Summary
Background and study aims
Metabolic syndrome refers to a clinical disorder where a group of conditions occur together.
These conditions are altered levels of fats and cholesterol in the blood, high blood pressure,
increased abdominal circumference (measurement around the waist), and high blood sugar levels
. This syndrome can be caused by a number of factors including activity levels, body weight, diet,
age, sex, ethnicity, and genetic profile. Together these conditions can cause chronic low-grade
inflammation and increase the risk of developing a set of diseases such as coronary heart disease
, stroke, and diabetes. A main complication of metabolic syndrome is the increased risk of
thromboembolism (a clot in a blood vessel that obstructs blood flow).
Inflammation is an important part of how the body responds to infections and injuries. However,
if inflammation occurs where it is not needed or the process goes on for too long, it can cause ill
health. Low-grade chronic inflammation is thought to be linked to a number of diseases such as
diabetes and heart disease. Some factors in the body that promote inflammation may be linked
to diet, lifestyle, pollution exposure, and infections. Inflammation is suspected to have a major
role in triggering metabolic syndrome.
This study aims to investigate whether a supplement of a Cannabis sativa seed oil (ALFALIFE™)
may improve the levels of metabolic markers in the body and reduce the level of low-grade
inflammation in addition to a balanced diet, in patients with a history of metabolic syndrome.
The study will also look at whether there are preventive effects on cardiovascular and lung
diseases, conditions such as diabetes, and low-grade inflammation, as well as inflammatory
syndromes following viral infections such as COVID-19 (a condition caused by a coronavirus
which can infect the respiratory system. This virus was first identified in 2019 and the outbreak
was declared a pandemic by the WHO in March 2020).
The study will also assess if the ALFALIFE™ supplement is safe and tolerable and whether it
improved the quality of life of the participants enrolled in the study
Who can participate?
Patients aged 40 to 69 with metabolic syndrome and low-grade inflammation or possible
low-grade inflammation who also have an insufficient dietary intake of alpha-linolenic acid.
What does the study involve?
Participants will be randomly assigned to one of two groups. One group will receive six capsules
of ALFALIFE™ (1 capsule with their breakfast, 2 with their lunch, and 3 with their supper) for 120
days, whilst the second group will receive a placebo, that will look exactly as ALFALIFE™. At the
start and end of the study, participants will have medical examinations, blood samples will be
taken, and will be asked to complete some questionnaires.
What are the possible benefits and risks of participating?
The subjects participating in the study will be checked on a regular basis to assess their health
conditions, their quality of life as well as their acceptance to the treatment. They will freely
receive their supplements and will receive medical advice during and at the end of the study,
based also on the results of the medical examination and the response to the treatment.
As long as the intervention is based on supplements with no known side effects, there are no
health safety issues related to the trial. However, the health status will be regularly checked and
any side effects promptly recorded and resolved.
Where is the study run from?
University hospital of the University of Insubria (Italy)
When is the study starting and how long is it expected to run for?
From June 2020 to October 2020
Who is funding the study?
Freia Farmaceutici s.r.l. (Italy)
Who is the main contact?
Dr Flavio Tangianu
flavio.tangianu@asst-settelaghi.it
Results and Publications
Publication and dissemination plan
Intention to publish date
30/04/2021
Participant level data
Other
Basic results (scientific)
Results (plain English)
Publication list
Publication citation(s)
Contact(s)
Contact
Type
Public
Title
Dr
Name
Flavio Tangianu
ORCID ID
Address
Viale Borri, 57
City
Varese
Country
Italy
Zip
21100
Tel
+39 (0)332 278 111
Email
flavio.tangianu@asst-settelaghi.it
Privacy
Public
Contact
Type
Scientific
Title
Prof
Name
Francesco Dentali
ORCID ID
https://orcid.org/0000-0003-4195-7725
Address
Viale Borri, 57
City
Varese
Country
Italy
Zip
21100
Tel
+39 (0)332 278 111
Email
francesco.dentali@uninsubria.it
Privacy
Public
Sponsor(s)
Sponsor
Organisation
University of Insubria
Address
Via Ravasi, 2
City
Varese
Country
Italy
Zip
21100
Tel
+39 800 011 398
Email
ateneo@pec.uninsubria.it
Type
University/education
Website
http://www.uninsubria.it
Privacy
Public
Funder(s)
Funding Type
Industry
Funder
Funder Name
Freia Farmaceutici Srl
Alternative Name(s)
Funding Body Type
Funding Body Subtype
Location
Applicant Details
Name
Fabio Capello
ORCID ID
Address
City
Country
Zip
Tel
Email
info@fabiocapello.net
Payment Method
Payment method
Online payment
Trusted funder
Invoice Details
Name
Institution
Address
City
State
Country
Zip
Email
Purchase order/ reference number
VAT number
Why did you choose ISRCTN to register your trial?
Previously registered a trial
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