Reducing Pain and Anxiety Through Dietary Fiber Supplementation in Children With Abdominal Pain

Study Overview
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Brief Summary
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Background - Mental health and pain problems in early childhood are major risk factors for serious mental health problems into adulthood. These long-term effects point toward the essential need for prevention and early intervention to curbing the rising tide of global mental health disease. New approaches to child and adolescent mental health are urgently needed. This study focus on children with functional abdominal pain (FAP), which is defined as recurrent abdominal pain independent of bowel movements without an underlying medical cause. This population has a high co-occurrence of anxiety and somatic complaints. The effects of fiber on gastrointestinal pain have not yet been tested in this group. The investigators propose that supplementation with dietary fiber (psyllium) in children with FAP will promote SCFA production by the gut microbiota, reducing abdominal pain and subsequently anxiety and improving quality of life. Psyllium promotes SCFA production, is considered safe, and meta-analyses have identified it as the most potent fiber for reducing abdominal complaints in IBS patients, indicating strong potential for reducing abdominal pain in children with FAP. It is essential that potential mechanisms through which psyllium-induced SCFA production can reduce abdominal pain and anxiety symptoms and improve quality of life are explored. This study will explore 3 mechanisms: 1) activation of the vagus nerve, as SCFAs can induce vagal signalling, and evidence suggests that vagus nerve stimulation can reduce pain and anxiety symptoms; 2) reduction in HPA-axis responsiveness, since fiber has been shown to do so in adults, and both abdominal pain and anxiety disorders are associated with increased HPA-axis activity; and 3) structural and functional brain changes in the amygdala and hippocampus, as SCFA can influence neuronal activity of specific brain regions and probiotics-induced improvements in mental health have been related to these brain regions in adults with IBS. Research question & Objectives - The first objective is to provide a dietary fiber psyllium supplement to children (ages 8-16 years) who suffer from FAP. The aims are to: 1) determine whether psyllium reduces abdominal pain, 2) investigate whether this subsequently decreases anxiety and improves quality of life, and 3) assess associated gut-brain axis mediators, specifically the vagus nerve, HPA-axis, and brain networks. Methods - The investigators propose a 12-week placebo-controlled double-blind parallel-group intervention pilot study (n=20/group) where children suffering from FAP will receive a daily supplement of either psyllium or placebo (maltodextrin). For participants aged 8-11 and weighing > 24 kgs, the dosage is daily 3 grams for 2 weeks followed by daily 6 grams for 10 weeks. For children aged 12-16 and weighing > 40 kgs, the dosage is daily 5 grams for 2 weeks followed by daily 10 grams for 10 weeks. An initial lower dose was chosen to allow the gastrointestinal tract to acclimatize to the increase in dietary fiber. The dosages were chosen based on the fact that this age group typically consumes 10g less dietary fiber than recommended. All study measures are collected prior to, and after the intervention. The primary measure is abdominal pain frequency and intensity during 7 consecutive days. Secondary measures include parent and child reported anxiety and quality of life. Stool samples are used to determine gut microbiota and SCFAs. MRI will be used to assess the role of brain regions implicated in pain and anxiety. Respiratory sinus arrhythmia during seated rest will be used to assess basal vagal tone.

Official Title
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Randomised, Blinded, Parallel, Placebo-controlled Study to Evaluate Whether Supplementation of the Dietary Fiber Psyllium Can Reduce Abdominal Pain and Improve Quality of Life and Anxiety in Children With Abdominal Pain.

Conditions
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Functional Abdominal Pain Syndrome

Intervention / Treatment
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* Dietary Supplement: Psyllium
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of functional abdominal pain as defined by the Rome IV criteria for childhood functional gastrointestinal disorders Exclusion Criteria: Diagnosis of inflammatory bowel disease or irritable bowel syndrome Lactose intolerance Abdominal surgery within the past year Contraindications for imaging Antibiotic use over the last 3 months

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Psyllium<br>For participants aged 8-11 and weighing > 24 kgs, the dosage is daily 3 grams for 2 weeks followed by daily 6 grams for 10 weeks. For children aged 12-16 and weighing > 40 kgs, the dosage is daily 5 grams for 2 weeks followed by daily 10 grams for 10 weeks. | Dietary Supplement: Psyllium<br>* See the information already included in the arm descriptions.<br>|
| Placebo Comparator: Placebo<br>For participants aged 8-11 and weighing > 24 kgs, the dosage is daily 3 grams for 2 weeks followed by daily 6 grams for 10 weeks. For children aged 12-16 and weighing > 40 kgs, the dosage is daily 5 grams for 2 weeks followed by daily 10 grams for 10 weeks. | Dietary Supplement: Placebo<br>* See the information already included in the arm descriptions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in abdominal pain scores as measured by an abdominal pain diary | The score minimum on the scale is 0, the maximum is 20. Higher scores indicate a worse outcome. The abdominal pain score diary is adapted from: See et al., 2001 - DOI: 10.1023/a:1010793408132 | Significant change from week-zero to week 12 between the active and placebo group | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anxiety scores as measured by PROMIS Anxiety scale | The Patient-Reported Outcomes Measurement Information System (PROMIS) questionaire will be used. The score minimum on the scale is 8, the maximum is 40. Higher scores indicate a worse outcome. | Significant change from week-zero to week 12 between the active and placebo group | 
| Quality of life as measured using the functional disability inventory (FDI) | The functional disability inventory (FDI) questionnaire will be used. The score minimum on the scale is 0, the maximum is 96. Higher scores indicate a worse outcome. | Significant change from week-zero to week 12 between the active and placebo group | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fiber, Psyllium, Quality of life, Gut microbiota, Anxiety, Pediatrics