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R E S E A R C H Open Access
Effectiveness of chiropractic manipulation
versus sham manipulation for recurrent
headaches in children aged 7–14 years - a
randomised clinical trial
Susanne Lynge
1
, Kristina Boe Dissing
2
, Werner Vach
3,4
, Henrik Wulff Christensen
3,5
and Lise Hestbaek
2,3*
Abstract
Background: To investigate the effectiveness of chiropractic spinal manipulation versus sham manipulation in
children aged 7–14 with recurrent headaches.
Methods: Design: A two-arm, single-blind, superiority randomised controlled trial.
Setting: One chiropractic clinic and one paediatric specialty practice in Denmark, November 2015 to August 2020.
Participants: 199 children aged 7 to 14 years, with at least one episode of headache per week for the previous 6
months and at least one musculoskeletal dysfunction identified.
Interventions: All participants received standard oral and written advice to reduce headaches. In addition, children in the active
treatment group received chiropractic spinal manipulation and children in the control group received sham manipulation for a
period of 4 months. Number and frequency of treatments were based on the chiropractor’s individual evaluation in the active
treatment group; the children in the control group received approximately eight visits during the treatment period.
Primary outcome measures: ‘Number of days with headache’,‘pain intensity’and ‘medication’were reported weekly by text
messages, and global perceived effect by text message after 4 months. A planned fixed sequence strategy based on an initial
outcome data analysis was used to prioritize outcomes. ‘Number of days with headache’and ‘pain intensity’were chosen as
equally important outcomes of highest priority, followed by global perceived effect and medication. The significance level for
the first two outcomes was fixed to 0.025 to take multiplicity into account.
Results: Chiropractic spinal manipulation resulted in significantly fewer days with headaches (reduction of 0.81 vs. 0.41, p= 0.019,
NNT = 7 for 20% improvement) and better global perceived effect (dichotomized into improved/not improved, OR = 2.8 (95% CI:
1.5–5.3), NNT = 5) compared with a sham manipulation procedure. There was no difference between groups for pain intensity
during headache episodes. Due to methodological shortcomings, no conclusions could be drawn about medication use.
(Continued on next page)
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* Correspondence: l.hestbaek@nikkb.dk
2
Department of Sports Science and Clinical Biomechanics, University of
Southern Denmark, Campusvej 55, 5230 Odense M, Denmark
3
Nordic Institute for Chiropractic and Clinical Biomechanics, Campusvej 55,
5230 Odense M, Denmark
Full list of author information is available at the end of the article
Lynge et al. Chiropractic & Manual Therapies (2021) 29:1
https://doi.org/10.1186/s12998-020-00360-3
(Continued from previous page)
Conclusions: Chiropractic spinal manipulation resulted in fewer headaches and higher global perceived effect, with only minor
side effects. It did not lower the intensity of the headaches.
Since the treatment is easily applicable, of low cost and minor side effects, chiropractic spinal manipulation might be considered
as a valuable treatment option for children with recurrent headaches.
Trial registration: ClinicalTrials.gov, identifier NCT02684916, registered 02/18/2016 –retrospectively registered.
Keywords: Ηeadache, Chiropractic, Children, Manipulation, Adolescents, Effectiveness, Clinical trial
Background
Recurrent paediatric headache is common with annual
prevalence rates ranging from approximately 5% among 3-
year-olds to more than half of the population around puberty
[1]. Recurrent headaches affect quality of life in children and
are known to interfere with school performance [2,3], social
life among peers and family [2], and participation in play and
sports [4]. Children with recurrent headaches also report
higher levels of stress and depression compared with chil-
dren without headache [3]. Importantly, suffering from re-
current childhood headache can be a precursor to potentially
severe headache syndromes later in life [5].
Paediatric headaches can be complex and are often asso-
ciated with co-morbid conditions [6,7] and the aetiology is
diverse, including familial disposition [8], psychological fac-
tors [9,10], nutrition [11], socioeconomic factors [7,12]
and more. Trauma to the head or neck, as well as pro-
longed static postures, have also been associated with head-
acheinchildren[13–15]. Thus, a biomechanical element
may be involved in the aetiology and therefore, spinal ma-
nipulation has been suggested as a treatment for headaches.
There is some evidence for the effectiveness of spinal ma-
nipulation in adults with chronic headache [16,17]. Spinal
manipulation is not uncommon for children with headache,
as it is the presenting symptom for 11–20% of school-aged
children and adolescents in chiropractic practice [18–20].
Nevertheless, with the exception of one small study where
the children only received a single manipulative treatment
[21], which is not common practice [16,22], there has not
been any formal investigation into the effectiveness of
spinal manipulation for children with recurrent headache.
Given the potentially severe consequences of recurrent
headaches in childhood and the risk of lifelong trajectories
of pain, safe and effective management needs to be identi-
fied. Adverse events following spinal manipulation appear
to be very rare [23] and the risk to be less than after taking
medication, which is often prescribed for painful condi-
tions [24]. Therefore, this approach calls for investigation.
Methods
Aim
The aim of this study is to investigate the effectiveness of
chiropractic spinal manipulation versus sham manipula-
tion in children aged 7–14 with recurrent headaches.
Trial design
This was a two-arm, single-blind, superiority random-
ized controlled trial. The protocol of the study has been
published elsewhere [25].
Participants
Between November 2015 and August 2019, we recruited
participants for this trial through the Danish School In-
formation Network, local newspapers, television, social
media and radio. The children had to be 7–14 years old,
to have experienced at least one episode of headache per
week for the previous 6 months and to have at least one
musculoskeletal dysfunction in the spine, pelvis and/or
temporomandibular joint, identified by the investigating
chiropractor. Exclusion criteria were examination find-
ings requiring immediate referral, contraindications to
spinal manipulation, previous treatment for headache
within the last 3 months and failure to report pre-
randomisation baseline data.
Setting
The study took place at two clinics in Northern
Denmark: one chiropractic clinic and one paediatric spe-
cialty practice. Screenings and treatments were adminis-
tered in both clinics by the same investigating
chiropractor with 34 years of experience in private
practice.
Pre-randomisation data collection
Before screening, eligible children and their parents an-
swered three questions each Sunday for 4 weeks via a
text message on their cell phone (Short Message System,
SMS). The questions regarded number of days with a
headache, intensity of headaches and number of pills
taken for headache during the previous week. In
addition, a pre-treatment questionnaire including the
characteristics of the child’s headache problem, lifestyle,
previous trauma, previous treatment, family history of
headache and general health was completed and
returned by mail. Details have been reported in the
protocol [25].
Lynge et al. Chiropractic & Manual Therapies (2021) 29:1 Page 2 of 13
Screening
After a four-week pre-treatment period, verifying at least
four episodes of headache, a screening for inclusion/ex-
clusion was done by the investigating chiropractor. This
included standard neurologic and orthopaedic examin-
ation, as well as examination for biomechanical dysfunc-
tions in the spine, pelvis and temporomandibular joints.
Randomisation
Upon receipt of the signed consent form, participating
children were randomised with 1:1 allocation using ran-
dom block size with the software nQuery Advisor [26]by
the data manager at the Nordic Institute for Chiropractic
and Clinical Biomechanics. Group assignment was noted
in opaque envelopes and sent to the project clinics.
After completing the four-week pre-treatment period
and confirmed as eligible for inclusion at the screening
visit, all participants and their parents received oral and
written advice believed to be beneficial to headache pa-
tients in general, regarding regular sleep, diet and exer-
cise. After this the randomisation envelope was opened
by the investigating chiropractor and the trial period of
4 months began.
Intervention
At all the visits, the participants’parents were present
during a short interview where information about side
effects and trauma experienced since the previous visit
was collected by the chiropractor. The parents would
then leave the room, and after examining the child, ei-
ther the chiropractic spinal manipulation or the sham
manipulation was administered.
The chiropractic spinal manipulation treatment was
directed at specific, individually identified dysfunctions
of one or more joints in the spine, pelvis and/or tem-
poromandibular joints. A high-velocity, low-amplitude
thrust, resulting in an audible cavitation, was given to
improve the function of the joint. The treatment has
been described in detail in the study protocol [25]. All
treatments were modified to fit the age and size of the
child as well as individual spinal characteristics. To re-
flect daily clinical practice, the number and frequency of
treatments, as well as the joints treated, were based on
the chiropractor’s individual evaluation at each visit
throughout the 4 months treatment period.
The sham manipulation treatment followed a previ-
ously validated protocol, developed by Chaibi et al. [27].
Placement of the child was similar to the placement in
the chiropractic spinal manipulation group, but low-
amplitude, low-velocity gentle pushes in a broad non-
specific contact away from the spinal column were given
with no resulting cavitation. In addition to the protocol
previously established by Chaibi et al., a de-activated ac-
tivator (www.activator.com)[28] on the chiropractor’s
own arm would produce a click-noise in connection
with the cervical treatment to resemble the sound of the
audible joint cavitation in the chiropractic spinal ma-
nipulation group. The children in this group should re-
ceive approximately eight visits with increasing intervals
during the 4 months participation period to resemble a
common course of care in a chiropractic practice. The
ideal schedule was 2 visits the first week, 1 visit/week
the following 2 weeks, 1 visit every other week for 4
weeks and finally the last two visits 4 weeks apart, but it
could be modified to the parents’convenience.
Post-intervention treatment
Children in the chiropractic spinal manipulation treat-
ment group who reported little or no effect, or a worsen-
ing of their headache after treatment were offered a
consultation with the paediatrician. Children in the sham
manipulation group who reported little or no effect, or a
worsening of headache after the trial period were offered
free chiropractic care, similar to the care delivered in the
spinal manipulation group. After the four-month post-
trial treatment period, parents received a final text mes-
sage, identical to the one they received after participating
in the trial regarding the effect of the treatment.
Outcomes
Throughout the study period, the parents together with
their participating children answered the same weekly
text messages as they had during the pre-randomisation
period:
1. “How many days has <child’s name> had a
headache this week? Choose a number between 0
and 7”.
2. “How will you rate the pain on a scale from 0-10,
where 0 is no pain and 10 is the worst pain you can
imagine?”
3. “How many pills for headache has < child’s name>
taken this week? 0: none, 1: 1-4, 2: more than 4
pills.”
The parents sent the answers using the reply function,
and the answers were automatically registered and
stored in a database. At the end of the 4 months of treat-
ment, all participating families received a final text mes-
sage including three questions to be answered in
collaboration between parents and child:
1. “How satisfied is <child’s name> with participation
in this trial on a scale from 0-10, where 0 is the
worst and 10 is the best you can imagine?”
2. “How has the headache changed since <child’s
name> started the treatment at the chiropractor? 1.
almost gone/disappeared; 2. much better; 3. slightly
Lynge et al. Chiropractic & Manual Therapies (2021) 29:1 Page 3 of 13
better; 4. same; 5. a little worse; 6. much worse; 7.
worse than ever.”
3. “In this trial there have been two groups. Do you
think that <child’s name< was in group 1, who had
standard chiropractic treatment or in group 2, that
DID NOT have standard chiropractic treatment
(please answer 1 or 2)?”
To estimate the effect of the intervention, we consid-
ered the average values during the pre-treatment period
and the final 4 weeks of the study period (Weeks 14–17)
for the three variables based on the weekly SMS ques-
tions. The final outcomes were then given by the change
scores, i.e. the difference between these average values.
A fourth outcome was the global perceived effect (GPE)
based on the SMS (question #2) after 4 months.
Sample size
A sample size calculation was conducted when the data
collection was completed for 50 children in each treat-
ment group [29]. This was based on weekly headache
days, and details were reported in the study protocol [25].
A sample size of 100 children in each group was indicated
to detect a difference of 20% in mean change score be-
tween groups with a power of 80% and a significance level
of 5%. Calculations were performed in nQuery Advisor
[26]. Allowing for a 20% drop-out rate, the aim for inclu-
sion was 240 children. However, as drop out was very rare,
inclusion was terminated after 199 children.
Blinding
Blinding the chiropractor was obviously not possible. Al-
location was concealed from the participants and their
parents and blinding was further attempted by including
a sham manipulation, closely resembling the active treat-
ment, including the clicking sound. At the end of the
treatment period, participating children and their par-
ents received a text message asking which group they
believed the child had participated in.
Initial outcome analysis
Due to a lack of experience with the four potential out-
comes in a population of children suffering from head-
ache and with an SMS-based data collection based on
responses from children and their parents, we did not
know whether they were measured in a reliable manner
and whether they would show a population variation
suitable to be used as an outcome in an RCT. For ex-
ample, we could not exclude that there would be little
variation in some of the intended outcomes across chil-
dren, or that we observed associations with baseline vari-
ables which were lower than expected and/or difficult to
explain. Such insights were needed to make an informed
prioritisation of the outcome variables. Therefore, we
conducted an interim outcome data analysis to avoid po-
tential misjudgments [30,31].
That interim analysis was performed blinded to inter-
vention status to provide information about the distribu-
tion of the four outcome variables in our population and
guide the final prioritisation of outcome measures. The
results of this analysis were discussed among the authors
and the resulting decision report was approved by all au-
thors before analyses of effects were initiated. The statis-
tical report and the final decision report can be found in
the Additional File 1.
The following main conclusions were drawn in the re-
port. Since some participants did not follow the instruc-
tions to cluster the number of medications in their SMS
responses and report the actual number, data on medi-
cation use could only be analysed in a reliable manner
by identifying the presence/absence of use each week.
Consequently, the corresponding primary outcome vari-
able was now the change in the proportion of weeks
with medication use. As many children did not report
any intake of medication in the pre-treatment phase, the
statistical report also suggested a sensitivity analysis,
which only included children with at least 2 weeks with
medication in the pre-treatment phase.
The vast majority of participants reported a pain in-
tensity of 0 in the weeks with no days of headache, in
line with our expectation. However, it turned out that
this led to a high variation in pain intensity over time for
many children. Hence, the definition of the four-week
pain scores was changed for intensity to take only weeks
with at least 1 day of headache into account. Rather than
illustrating the average intensity, this reflects the inten-
sity of the headaches when present. In addition, two fur-
ther intensity definitions were suggested to be included
in the sensitivity analyses: the original definition and the
average over the last available 4 weeks with headache,
but maximally going back 7 weeks from the end of the
treatment period. Lastly, the statistical report suggested
the inclusion of an analysis of lower percentiles of the
change scores, instead of means, as a sensitivity analysis
to cover the scenario of only a few children benefiting
from the intervention.
Based on the above, ‘number of days with headache’
and ‘pain intensity’were chosen as equally important
outcomes of highest priority, followed by GPE and then
medication. The significance level for the first two out-
comes was fixed to 0.025 to take multiplicity into ac-
count within the planned fixed sequence strategy.
Statistical analyses
All analyses were performed and presented to all authors
for interpretation blinded for intervention status and
two alternative conclusions were formulated before the
concealment was broken. Baseline characteristics are
Lynge et al. Chiropractic & Manual Therapies (2021) 29:1 Page 4 of 13
reported as frequencies in each treatment arm for binary
and categorical variables, and as means for continuous
variables. To illustrate the spread of the data, means are
supplemented with 10th and 90th percentiles. With re-
spect to previous examinations, previous treatments and
reasons for school absence due to illness, the frequencies
for the most common category are reported.
The distribution of the primary outcomes in each
treatment group is illustrated by dot plots. Intervention
effects are assessed by the difference in mean values be-
tween the two intervention groups. They are supple-
mented by t-test-based 95% confidence intervals, p-
values and Cohen’s d (standardized mean difference be-
tween groups) as a measure of effect size. In addition,
we present adjusted p-values based on a linear regres-
sion model with one covariate in addition to treatment.
That covariate was the baseline level for each of the
change scores, and the number of days with headache at
baseline for GPE. According to the protocol, an adjust-
ment for additional baseline characteristics was planned
in case they showed a correlation of at least 0.3 with the
outcome variable. However, no such characteristic was
identified. The multiplicity implied by considering four
primary outcomes was taken into account by applying a
fixed sequence strategy according to the prioritisation
resulting from the initial outcome data analyses. Signifi-
cance levels of 0.025 for the first two primary outcomes
and 0.05 for the two remaining were used and applied to
the adjusted p-values.
For the three change scores, a responder analysis was
conducted, reporting the proportion in each group with
20, 25, 50 and 75% improvement compared with base-
line. The number needed to treat (NNT) to reach a 20%
improvement is also reported. In order to decide
whether to refer the child to a paediatrician after the
follow-up period, GPE was dichotomised into ‘improved’
or ‘same or worse’[25]. The same dichotomisation was
used to calculate NNT and this also allowed calculation
of an odds ratio.
Side effects and satisfaction with care are analysed as
secondary outomes (the latter not mentioned in the
study protocol). In addition, course of treatment and the
parents’guess about treatment group are reported by
group. Results for the pre-specified secondary outcomes,
headache status and GPE after 8 and 12 months, will be
presented in a subsequent manuscript.
Aligned with the protocol, sensitivity analyses were per-
formed with missing values imputed based on multiple
imputation (described in detail in Additional File 2). In
addition, the sensitivity analyses according to the initial
outcome data analysis report were performed.
The study is reported according to the CONSORT
guidelines [32] and a CONSORT check list is included
as Additional File 3.
STATA v.16.0 (StataCorp, College Station, Tx, USA)
was used for all analyses.
Ethics
All parents were required to give written informed con-
sent allowing their child to participate in this study and
they were informed orally and in writing that participation
in the trial was voluntary and that parents could withdraw
their child from the trial at any time with no negative con-
sequences for the child. All participants were treated ac-
cording to the Declaration of Helsinki [33].
The project was approved by the Regional Committee
on Health Research Ethics for The North Denmark Re-
gion (#N-20150025) and data were handled according to
the General Data Protection Regulations [34]. The trial
was registered with ClinicalTrials.gov (Identifier:
NCT02684916) [35].
Results
Recruitment and dropouts
The inclusion period lasted from November 1st 2015 to Sep-
tember 2nd 2019. Of the 253 children screened, 199 (79%)
children were eligible for inclusion. Of these, 99 were rando-
mised to the intervention group, and 100 to the control
group. Five children dropped out during the four-month trial
period for reasons unrelated to treatment (Fig. 1).
In some children, the weekly SMS data were missing
for some weeks or single items were missing. Hence the
averages used to compute change scores were based on
less than 4 weeks for some individuals. Details are given
in Additional File 4.
Patient characteristics at baseline
There were more girls (57%) than boys in the cohort
and the mean age at baseline was 10.8 years. The mean
pain intensity at baseline was 6.0 and the vast majority
of children had taken non-prescriptive medicine at some
point, most often 1–3 times per month, but only 4% had
taken prescriptive medicine. Approximately half of the
children had been seen by a general practitioner for their
headache, but only one-fifth had received treatment for
their headache, most often by a chiropractor. Approxi-
mately three-quarters of the children reported previous
trauma to the head and/or neck, and headache was by
far the primary reason for absence from school due to
illness. The majority of the children were physically ac-
tive during leisure time and had a sufficient amount of
sleep. Baseline distribution of age, sex and the outcomes
are shown in Table 1and further details are presented
in Additional File 5, Supplementary Table 1.
Headache characteristics at baseline
Approximately half the children had experienced recur-
rent headaches for 1 to 3 years, most often a few days
Lynge et al. Chiropractic & Manual Therapies (2021) 29:1 Page 5 of 13
per week, but 13% suffered from headache almost every
day. An episode of headache lasted typically from 2 to
12 h per day and the onset varied over day and night.
The typical region of onset varied across children, but
headache was often located at the forehead. The most
predominant co-occurring symptoms were nausea,
dizziness, light and sound sensitivity (53–61%). Neck
pain (48%) and the use of computer/tv (51%) were the
activities most often thought to cause headache, whereas
sleeping was the main activity easing the headache
(83%). Further details are presented in Additional File 5,
Supplementary Table 2.
Fig. 1 Consort flowchart
Table 1 Baseline values of sex, age and outcome measures. Additional baseline characteristics are shown in Additional File 5,
Supplementary Table 1
Intervention group (N= 99) Control group (N= 100)
Sex, boys, n (%) 45 (45%) 40 (40%)
Age (mean, SD) 10.9 (2.1) 10.7 (2.0)
Number of days/week
a
(mean, SD) 2.8 (1.4) 2.8 (1.5)
Pain intensity
a
(NRS) (mean, SD) 5.2 (1.4) 5.3 (1.4)
Medication
b
(mean, SD) 0.5 (0.3) 0.4 (0.4)
a
within a 4-week period at baseline,
b
proportion of weeks with medication use
Lynge et al. Chiropractic & Manual Therapies (2021) 29:1 Page 6 of 13
Analysis of primary outcomes
Table 2and Figs. 2and 3describe the results for the pri-
mary outcomes.
Number of days
In both treatment groups, we observed a substantial
variation in the change in number of days with a ten-
dency to more substantial improvements in the interven-
tion group (Fig. 2). On average, children reported fewer
days with headache after the four-month follow up in
both groups compared with baseline, however the mean
reduction in number of days with headache was twice as
high for children in the intervention group compared
with the control group (0.81 vs. 0.41), which was statisti-
cally significant (Table 2). The effect size (Cohen’sd)
was 0.32. From the responder analysis, illustrated in
Fig. 3, it can be seen that about one-third of the children
displayed more than a 50% improvement with response
being more frequent in the intervention group. The
NNT to reach 20% improvement was 7.
Intensity
Regarding intensity of headache, we can observe a reduc-
tion over time for many children in both groups (Fig. 2).
The mean reduction was almost equal between the two
groups (0.53 vs. 0.52) and the difference was not statisti-
cally significant (Table 2). The effect size (Cohen’sd)was
0.01. In the responder analysis illustrated in Fig. 3,less
than a third of the children showed an improvement of at
least 20%. The difference between the groups was of negli-
gible magnitude. The NNT to reach 20% improvement
was 50.
Global perceived effect
As illustrated in Fig. 2, improvement in GPE was more
frequent in the intervention group. The mean score was
3.2 in the intervention group and 2.6 in the control
group. The difference in mean scoring was significant
with a value of 0.61, corresponding to a Cohen’sdof
0.67 (Table 2). When dichotomised, 43.4% reported im-
provement in the intervention group and 22.0% in the
control group, resulting in an odds ratio of 2.8 (95% CI:
1.5–5.3). The number needed to treat was 5.
Medicine
As illustrated in Fig. 2, intake of medicine went up or
down to a similar degree in both groups, resulting in
small reductions on average (Table 2). There was no sta-
tistically significant difference detected between groups
(0.10 vs. 0.03). Cohen’s d was 0.20. In the responder ana-
lysis seen in Fig. 3, both groups showed an almost equal
improvement, resulting in an NNT of 40 to reach 20%
improvement.
Secondary outcomes
In the intervention group, 84% of the children reported
side effects following at least one consultation and in the
control group it was 75%. Side effects reported were
mild in nature, most often soreness, headache and fa-
tigue, and they were typically of short duration (0–2 h).
There were no serious side effects reported. Details are
reported in Additional File 5, Supplementary Table 3.
As seen in Fig. 4, most children were quite satisfied
with participation in the trial, but children in the inter-
vention group were on average more satisfied than chil-
dren in the control group. The difference was
statistically significant (p< 0.001) with a mean of 7.9 ver-
sus 6.8 for the intervention and the control group, re-
spectively. Cohen’s d was 0.49.
Course of treatment and guessing of treatment group
We intended to expose the children to treatment for 17
weeks and this was achieved in the intervention group,
with a median of 16.8 weeks and little variation (10th–
90th percentile: 15.7–17.7). The median time was
smaller in the control group (15.0) with a more substan-
tial variation (12.3–18.6). There was, however, a distinct
difference in the number of consultations, with a median
of 11 in the intervention group and 7 in the control
group. This reflects a difference in the time scheduling
of the consultations. In the control group, we reached
the intended gap of 14 days between consultations quite
precisely with a median of 14 days, whereas in the inter-
vention group the median was 9 days.
At the four-month follow up, 62% in the intervention
group and 59% in the control group guessed the correct
randomisation group.
Table 2 Results on the four primary outcomes
Control Intervention
Outcome N Mean N Mean Difference in mean (95% CI) p-value p-value** Cohen’s d***
Number of days per week* 97 −0.41 96 −0.81 −0.40 (−0.77; −0.05) 0.027 0.019 0.32
Intensity (NRS)* 93 −0.53 90 −0.52 0.01 (−0.43; 0.46) 0.958 0.930 0.01
GPE 98 3.24 96 2.63 −0.61 (−0.88; −0.36) < 0.001 < 0.001 0.67
Medicine*# 97 −0.03 96 −0.10 −0.07 (−0.16; 0.03) 0.165 0.279 0.20
Nnumber of children, CI confidence interval, NRS numerical rating scale, GPE global perceived effect (1 = almost gone to 7 = worse than ever)
*change scores from baseline to follow up; **adjusted p-value; ***standardi zed mean difference between groups; # proportion of weeks with medication use
Lynge et al. Chiropractic & Manual Therapies (2021) 29:1 Page 7 of 13
Fig. 2 Change in the four primary outcomes by treatment group. The size of the symbols is proportional to the number of children
Lynge et al. Chiropractic & Manual Therapies (2021) 29:1 Page 8 of 13
Sensitivity analyses
Using different definitions of outcomes - as suggested in
the initial outcome data analysis report - did not change
the results, except for the case of using the original def-
inition for pain intensity. In this case, the results trended
towards those observed for number of days with head-
ache, as we expected from our considerations in the ini-
tial outcome data analysis (Additional File 5,
Supplementary Table 4). The handling of missing values
did not seem to affect the results (Additional File 2,
Supplementary Tables 5–6). We did not perform ana-
lyses of percentiles, as the analysis of mean values gave a
clear picture.
Discussion
Principal findings
This is the first large-scale randomised clinical trial in-
vestigating the effectiveness of chiropractic spinal ma-
nipulation in the treatment of recurrent headaches in
children. Chiropractic spinal manipulation resulted in
Fig. 3 Responder analysis, including NNT, for the three continuous outcomes
Lynge et al. Chiropractic & Manual Therapies (2021) 29:1 Page 9 of 13
significantly fewer days with headaches and better GPE
when compared with a validated sham manipulation
procedure. There was no difference between groups for
pain intensity during headache episodes.
Previous literature
This positive effect is in line with results seen in studies
of adult populations for migraine [36] and cervicogenic
headaches [17,37], whereas the results for tension type
headaches are favorable but less conclusive [16,17]. Also
in trials in adults, effects of manual therapy were more
pronounced for frequency of headache than for pain in-
tensity [16,22].
However, the results presented in this article do not
distinguish between headache types in the children. Fur-
thermore, it should be noted, that the effect of placebo
is possibly larger for children than adults [38], and thus
larger effects are needed to demonstrate differences be-
tween treatment and sham interventions.
Strengths and weaknesses
The use of an adaptive design [29–31] allowing for the
prioritisation of the primary outcomes based on an in-
terim analysis might be considered unorthodox. How-
ever, due to the uncertainty about the measurement
properties of the outcomes included, we believed this
step to be necessary in order to avoid misjudgments in
the priority of outcomes. Actually, the interim analysis
led to a down-grading of the outcome medication, which
otherwise would probably have been given a higher pri-
ority. The interim analysis was pre-planned, blinded for
any information about the treatment status of the par-
ticipant, and performed by an independent statistician,
and thus the scientific standard was not compromised.
The process was transparent, and the reports are pub-
lished in the supplementary material.
This study has several strengths. The good compliance
and the large sample size resulted in more precise esti-
mates and can facilitate subsequent hypothesis-
generating subgroup analyses; utilising weekly SMS text
messages as a headache diary reduces recall bias and has
been shown to be an efficient and reliable method to
collect frequent data [39,40]; and there has been a
structured recording of side effect/adverse event. The
blinding appeared to be effective because the observed
difference in belief between groups is understandable
due to the better outcome in the treatment group likely
to have fostered a belief that they received the active
treatment [41].
The treatment was individualised with attention to any
specific biomechanical dysfunction the child might have
had, rather than a standardised treatment given to all. This
reflects clinical reality and is likely to make potential rec-
ommendations easier to translate into common practice.
We regard having the same, highly experienced chiro-
practor treating both groups as a way to reach similarity
of the clinical encounter across groups, with the only ex-
ception being the chiropractic spinal manipulation [42]
instead of the sham manipulation. However, we cannot
exclude deviations from this optimal scenario due to
lack of blinding. Using a highly experienced chiropractor
may also question the transferability of results, but using
an expertise-based approach can prove to be a strength
for the community to subsequently trust and embrace
the findings [43]. Future studies must determine the
level of expertise needed to obtain similar results.
Fig. 4 Proportion of children satisfied with participation in the trial as reported by their parents
Lynge et al. Chiropractic & Manual Therapies (2021) 29:1 Page 10 of 13
On average the control group had nearly the intended
number of eight consultations over a 16-week period
and the intended gap of 14 days between consultations
on average, whereas the active treatment group received
on average 11 consultations. This is clearly above our
expectations for the active treatment group and is due to
the fact, that the treatment was pragmatic, i.e. based on
the children’s signs and symptoms at each visit, and
therefore these could not be precisely planned and did
not follow a predefined protocol. On the other hand, the
control children followed the predefined pattern of visits
to the extent that the parents’and the clinician’s sched-
ules allowed. It cannot be excluded that the favorable re-
sults for patients in the active treatment group are
partially due to obtaining more attention - both in quan-
tity and quality. However, the control group actually re-
ceived an unusually high level of quantitative attention
compared to patients not included in this study, such
that the effect of additional attention may be limited.
Unfortunately, medication use could not be evaluated in
this study due to difficulties interpreting the responses as
described in the decision report. Future studies should at-
tempt better ways to include use of medication since the
risk of Medication Overuse Headache increases with age
[8] and the use of over-the-counter painkillers is worry-
ingly high in adolescence, primarily due to headache [44].
Implications
Considering the significant consequences of paediatric
headache and the lack of effective and safe pharmaco-
logical treatment [1,3,38], non-pharmacological treat-
ments such as spinal manipulation could be attractive
alternatives [45]. The positive results from this study
combined with the low risk of adverse events should en-
courage clinicians and policy-makers to consider spinal
manipulation for children with recurrent headaches.
Unanswered questions and future research
The most important next step is investigating of the
long-term effect. One-year follow-up is being completed
for the present study and will be reported in a later art-
icle. The difference in effect of treatment between GPE
(NNT = 3) and frequency (NNT = 7), and the lack of ef-
fect on intensity, might imply that frequency and pain
intensity alone do not adequately capture ‘improvement’
as experienced by the children. This indicates that there
are elements of improvement which are not captured by
the investigated outcomes. Before future trials of ma-
nipulation or other types of treatment for paediatric
headaches are initiated, qualitative studies should inves-
tigate further which outcomes are important to children.
Furthermore, considering the complexity of childhood
headaches and the large individual differences in re-
sponse to treatment observed in this study, it is
important to identify potential treatment effect modifiers
to target treatment efficiently.
Conclusion
We found that children with recurrent headaches who
received chiropractic spinal manipulation experienced
fewer days with headaches compared with children re-
ceiving sham manipulation. We could not detect a rele-
vant difference in pain intensity between the groups.
Children receiving chiropractic spinal manipulation also
reported higher self-rated improvement than children
receiving sham manipulation. Unfortunately, medication
data were unreliable and therefore no conclusions could
be drawn on this.
Consequently, since the treatment is easily applicable,
of low cost and with no or only mild side effects, chiro-
practic spinal manipulation might be considered as a
valuable treatment option for children with recurrent
headache.
Supplementary Information
The online version contains supplementary material available at https://doi.
org/10.1186/s12998-020-00360-3.
Additional file 1. The results of the initial outcome data analysis and
the resulting decision report.
Additional file 2. Tables showing results following imputation of data.
Additional file 3. Full reporting check list including page numbers.
Additional file 4. Flowchart of SMS-reports.
Additional file 5. Additional information in tables.
Abbreviations
GPE: General Perceived Effect; NNT: Numbers Needed to Treat;
NRS: Numerical Rating Scale; SMS: Short Message Service
Acknowledgements
We would like to acknowledge Suzanne Capell for providing professional
proofreading service.
Authors’contributions
SL and LH conceived the idea; SL, LH and HWC designed the study; SL
collected the data; KBD and WV performed the data analyses; SL and LH
prepared the draft manuscript; all authors participated in the interpretation
of data; all authors read and approved the final manuscript.
Funding
The study was primarily funded by the Foundation for Chiropractic Research
and Postgraduate Education (Grant no 09/2518). The Danish Migraine and
Headache Society also made a financial contribution. The funding bodies did
not have any influence on the study design; in the collection, analysis, and
interpretation of data; in the writing of the report; or in the decision to
submit the article for publication. All authors had full access to all data
(including statistical reports and tables) in the study and can take
responsibility for the integrity of the data and the accuracy of the data
analysis.
Availability of data and materials
Relevant anonymised data are available from the corresponding author on
reasonable request.
Lynge et al. Chiropractic & Manual Therapies (2021) 29:1 Page 11 of 13
Ethics approval and consent to participate
All parents were required to give written informed consent allowing their
child to participate in this study and they were informed orally and in
writing that participation in the trial was voluntary and that parents could
withdraw their child from the trial at any time with no negative
consequences for the child. All participants were treated according to the
Declaration of Helsinki [33].
The project was approved by the Regional Committee on Health Research
Ethics for the Region of Northern Denmark (#N-20150025) and data were
handled according to the General Data Protection Regulations [34]. The trial
was registered with ClinicalTrials.gov (Identifier: NCT02684916) [35].
Consent for publication
N/A.
Competing interests
LH, WV and HWC are supported partly by the Foundation for Chiropractic
Research and Postgraduate Education; SL, HWC and KBD are in private
practice, treating the patients in question. No other relationships or activities
that could appear to have influenced the submitted work.
Author details
1
Private Chiropractic Practice, Vivaldisvej 6, 9700 Broenderslev, Denmark.
2
Department of Sports Science and Clinical Biomechanics, University of
Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
3
Nordic
Institute for Chiropractic and Clinical Biomechanics, Campusvej 55, 5230
Odense M, Denmark.
4
Basel Academy, Steinenring 6, 4054 Basel, Switzerland.
5
Private Chiropractic Practice, Enghavevej 2, 5800 Nyborg, Denmark.
Received: 10 August 2020 Accepted: 14 December 2020
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