Clinical trial NCT05636358: Hypnotherapy Through Self-exercises in Children With Functional Abdominal Pain in Primary Care
Official title: Hypnotherapy Through Self-exercises in Children With Functional Abdominal Pain in Primary Care
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Functional Gastrointestinal Disorders
Irritable Bowel Syndrome
Functional Abdominal Pain Syndrome
Keywords: Primary care
Children and adolescents
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2022-12-05
Enrollment: 152
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a pragmatic randomised controlled trial (RCT) with a total follow-up of 12 months executed in primary care in the Netherlands. Participating children will be randomised 1:1 on the patient level to either the intervention or the care as usual group. The intervention group will receive 3 months home-based hypnotherapy by self-exercises in addition to care as usual by their GPs according to the Dutch Society of GPs' (NHG) guideline. The control group will receive usual care (UC) by their GPs alone according to the Dutch Society of GPs' (NHG) guideline.
Primary purpose: TREATMENT

Brief summary: The goal of this randomised controlled trial is to study the (cost-)effectiveness of home-based hypnotherapy by self-exercises in children with functional abdominal pain (FAP) or irritable bowel syndrome (IBS) in primary care. The main questions it aims to answer are:

* What is the effect of home-based hypnotherapy by self-exercises on adequate relief of abdominal pain and discomfort in addition to care as usual of general practitioners (GPs), compared to care as usual of GPs alone in children with FAP or IBS?
* What is the effect of home-based hypnotherapy by self-exercises in addition to care as usual by GPs compared to care as usual of GPs alone in children with FAP or IBS on:

  * Frequency and intensity of abdominal pain and discomfort
  * Pain severity
  * Daily functioning and impact
  * Anxiety and depression
  * Pain beliefs
  * Sleep disturbances
  * School absence
  * Use of health care services, including GP visits and referrals to secondary care
  * Costs (healthcare and societal perspective)

Participants in the intervention group will receive home-based hypnotherapy 5 times a week for approximately 15-20 minutes a day during 3 months in addition to care as usual by their GP according to the Dutch society of GPs' guideline for children with abdominal pain.

Participants in the control group will receive care as usual by their GP according to the Dutch society of GPs' guideline for children with abdominal pain.

Detailed description: Recruitment

This study will be performed within the network of GPs connected to the Department of General Practice of the UMCG (Academisch Huisarts Ontwikkel Netwerk, AHON).

Children and/or parents visiting the GP with chronic gastrointestinal symptoms (at least 4 days per month during the past 2 months), who had none of the exclusion criteria, will be approached by their general practitioner (GP), either during consultation or following monthly retrospective search of medical records. The GP fills out the study response form including the in- and exclusion criteria and the contact details of the child and/or parents. If the child seems eligible, the child and/or parents will receive the patient information letter. If the child and/or parents are interested in study participation and provide permission, the GP will send the response form to the research team.

To further improve patient recruitment, since August 2022 children and parents are informed through schools, (social) media and the study website. Information includes background on functional abdominal pain (FAP) and irritable bowel syndrome (IBS), hypnotherapy, the current study, and contact information of the research group. The researchers will contact children and/or parents who apply for participation by telephone. The researcher will answer questions and check eligibility criteria. If the child wishes to participate, the researcher sends the PIF and informed consent (IC) forms via a REDCap link to their e-mail address. In the same e-mail, the researcher informs how their GP can find information and the digital response form on the study website. The GP will check the in- and exclusion criteria prior to participation and directly submits the form to the researchers on the study website.

The researcher/research assistant will approach the eligible children and/or parents by telephone within one week after receiving their response form. During the call the researcher/research assistant fills out the Rome IV criteria questionnaire and checks whether the child and/or parents are motivated and willing to participate. Questions by the child and/or parents will be answered. If the child is willing to participate, the researcher/research assistant will inform the child and/or parents, and send the IC forms via a REDCap link to their e-mail address to those who were included directly during consultation. If preferred, the second contact moment may also be face-to-face in the GP's practice instead. A follow-up visit at the GP 4 weeks after inclusion should also be scheduled. If the child does not want to be randomised, the child and/or parents are asked whether they are willing to participate in a cohort. Here, children with chronic abdominal pain and their parents will not participate in the RCT, but they will fill out primary and secondary parameters like in the RCT at baseline and during follow-up via the online system REDCap. If they are willing to participate in the cohort, they will also receive IC forms to be signed via REDCap. The research team will continuously monitor the return of the IC forms, and will call the child and/or parents if they do not return the forms. If child and/or parent(s) prefer written information and IC, the patient information package including a return envelope can be sent by regular post.

After signing the digital IC forms in REDCap, all children and/or parents will be asked to fill-out the baseline parameters online via a digital link from REDCap. They cannot begin with the questionnaires before giving informed consent. Next, randomisation will be performed. The result from the randomisation procedure will be discussed during the second telephone call by the research team and the child and/or parents. During this call the researcher/research assistant will also inform the IG about intervention procedures. The workbook in the online portal is leading and self-explanatory. Questions will be answered. Afterwards, the intervention group (IG) will receive access to the home-based hypnotherapy self-exercises for 3 months via a login to the closed part of the website/portal. All children in both the RCT and the cohort will fill out the required primary and secondary parameters at baseline, 3, 6 and 12 months through the digital REDCap application.

Overall, the GP remains responsible for the medical health of the children and will respond to any medical issues or related questions. The researchers are responsible for guiding the practical questions in relation to the study. To help the child and/or parents with practical issues, the public part of the website/portal contains a section on frequently asked questions (FAQ).

Statistical analysis In general, the researchers will use appropriate descriptive statistics and frequencies to summarize the collected primary and secondary outcomes at baseline and during follow-up.

Primary study outcomes

The primary outcome is the proportion of children with self-identified adequate relief of abdominal pain/discomfort (yes/no) after 12 months follow-up in the intervention group versus the care as usual group. The researchers will perform an intention to treat in a primary analysis and per protocol in a secondary analysis. The intention to treat population includes all children with signed IC, who have been randomised (despite what treatment they have in fact received). The per protocol population includes the children, who in fact have had the home-based hypnotherapy self-exercises and the control group, who in fact had no home-based hypnotherapy self-exercises.

A missing value analysis will be performed and if missing values are more than 5% and considered missing at random (MAR), data will be imputed by multiple imputation. The primary outcome is analyzed with an intention-to-treat analysis using a multivariable logistic regression model. Covariates taken into consideration include the stratification factor based upon age (\<12 years versus ≥12 years), baseline pain severity score (NRS-11) and treatment expectations of the child and parents at baseline. Both a complete cases analysis and an analysis with the imputed data (if the missing data are considered MAR) will be performed. A secondary per protocol analysis of the responders in the IG will be performed based on adequate use of the intervention. Adequate use is defined as listening to one of the exercises for at least 80% of the time.

Secondary study outcomes

The researchers will use logistic and linear multilevel analyses to investigate the longitudinal relationship between the intervention group and the control group with respect to the various secondary outcome variables. This includes the frequency and intensity of the abdominal pain/discomfort, school absence, anxiety and depression, pain beliefs, functional impairment and impact, sleep scores and healthcare use. The applied levels will be the repeated measures (the time - baseline, 3 months, 6 months and 12 months) and the patient groups respectively.

The cost effectiveness will be measured with a time horizon of 12 months, and costs will be calculated from a societal perspective. The cost-effectiveness analysis will include the primary outcome, expressing the additional costs or savings per additional patient with adequate relief of symptoms. Data regarding health care consumption and productivity losses will be collected on a patient level. Cost categories to be included are for example costs of the online intervention application, GP and specialist visits, medication, and productivity losses of parents. The cost questionnaire and the medical records of the participating child will be used to collect data regarding health care consumption and productivity losses. These items will be valued using standard prices from the Zorginstituut and medicijnkosten.nl when possible. For the use of the online intervention application, a cost price will be calculated based on true resources used. Costs between the two treatment arms will be compared. In the cost utility analysis, patient outcome will be measured using the EuroQoL Youth (EQ-5D-Y) and compared per study group.

Other study parameters

Patient descriptive data, Rome IV criteria, treatment expectations, frequency and intensity of the use of the hypnotherapy self-exercises and co-morbid somatization problems will be presented with the appropriate descriptive statistics and frequencies to summarize the information. School level and treatment expectations will be incorporated as covariates in the analyses of the primary outcome. Usage of the hypnotherapy self-exercises will be integrated in the responder analysis of the intervention group.

Sample size calculation

Based on earlier research, the researchers expect adequate relief in 55% of the children in the usual care group and 75% in the intervention group. In order to detect this difference of 20%, with 80% power and 5% significance level a randomised study would require 180 children (90 per group). When taking into account a total loss during follow-up of 10%, the researchers need to include 200 children (100 per group) for this study.

Handling and storage of data and documents

All consecutive patients, who meet the inclusion criteria, will receive a unique study number, assigned by the coordinating investigator. The study number is not based on the patient's initials and birth-data. The study number will be composed of the number of inclusion and the stratification group (\<12 years or ≥12 years). All data will be collected and stored linked to this number. All patients, who gave written IC for the study, will complete digital questionnaires via a hyperlink to REDCap send by e-mail, which will automatically be linked to the corresponding study ID. The coordinator investigator has access to the full subject identification code lists in order to able to link patients to the corresponding study number. A password is needed for entering this link file. Data will be stored during the study period and until 15 years thereafter when the parents give permission.

Monitoring and quality assurance

As this study is with negligible risks a monitor from the UMCG Monitor pool will monitor the study once 50 participants are recruited. A qualified monitor (research assistant at the Department of General Practice and Elderly Care Medicine, UMCG) has prepared a concept monitoring plan, including specification of the methods, frequency and extent of the monitoring.

Eligibility criteria: Inclusion Criteria:

* Aged 7 to 17 years
* GP visit concerning chronic gastrointestinal symptoms
* FAP or IBS according to their GP

Exclusion Criteria:

* A concomitant organic gastrointestinal disease
* Treatment by a paediatrician for abdominal symptoms
* Intellectual disability
* A history of a psychotic disorder
* Hypnotherapy treatment in the past year
* Insufficient knowledge of the Dutch language by the child or parents

Primary outcomes:
measure: Adequate relief at 12 months
timeFrame: 12 months
Secondary outcomes:
measure: Adequate relief at 3 and 6 months
timeFrame: 3 and 6 months
measure: Pain frequency and intensity
timeFrame: 0, 3, 6, and 12 months
measure: Severity of pain
timeFrame: 0, 3, 6, and 12 months
measure: Daily functioning and impact
timeFrame: 0, 3, 6, and 12 months
measure: Anxiety and depression
timeFrame: 0, 3, 6, and 12 months
measure: Pain beliefs
timeFrame: 0, 3, 6, and 12 months
measure: Sleep disturbances
timeFrame: 0, 3, 6, and 12 months
measure: School absence
timeFrame: 0, 3, 6, and 12 months
measure: Healthcare consumption
timeFrame: 0, 3, 6, and 12 months
measure: Cost-effectiveness
timeFrame: 0, 3, 6, and 12 months
measure: Cost-utility
timeFrame: 0, 3, 6, and 12 months
Other outcomes:
measure: Patient baseline characteristics
timeFrame: Baseline
measure: Paediatric gastrointestinal symptoms
timeFrame: Baseline
measure: Usage of hypnotherapy self-exercises
timeFrame: 3 months
measure: Treatment expectations
timeFrame: Baseline
measure: Quality of exercises
timeFrame: 3 months
measure: Somatisation
timeFrame: 0, 3, 6, and 12 months
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Marjolein Y. Berger, prof
role: PRINCIPAL_INVESTIGATOR
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