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

Functional Abdominal Pain Syndrome Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04619095
• Other study ID #: REB20-1373
• Status: Withdrawn
• Phase: N/A
• Start date: June 1, 2022
• Est. completion date: November 1, 2023

Study information

• Verified date: September 2021
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 1, 2023
• Est. primary completion date: November 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 16 Years

Eligibility

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

Related Conditions & MeSH terms

• Abdominal Pain
• Functional Abdominal Pain Syndrome

Intervention

Dietary Supplement:
• Psyllium
See the information already included in the arm descriptions.
• Placebo
See the information already included in the arm descriptions.

Locations

Country	Name	City	State
Canada	Pediatric GI Motility Laboratory at Alberta Children's Hospital	Calgary	Alberta

Sponsors (2)

Lead Sponsor	Collaborator
University of Calgary	Alberta Children's Hospital Research Institute

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Stool microbiome - Stool samples will be assayed using metagenome shotgun sequencing, after which alpha diversity is assessed.	Alpha diversity will be assessed using the Shannon diversity index.	Significant change in alpha diversity from week-zero to week 12 between the active and placebo group
Other	Stool metabolome - Stool samples will be assayed using liquid chromatography-mass spectrometry for short-chain fatty acid levels	Short-chain fatty acid levels are expressed as mM.	Significant change in short-chain fatty acid levels from week-zero to week 12 between the active and placebo group
Other	Respiratory sinus arrhythmia.This will be quantified using the high-frequency component of heart-rate variability.	Vagus nerve activity will be measured indirectly using respiratory sinus arrhythmia.	Significant change from week-zero to week 12 between the active and placebo group
Other	Both structural and functional MRI will be used to quantify changes in connectivity between the amygdala and prefrontal cortex.	Connectivity will be expressed as a z-score.	Significant change in amygdala-prefrontal cortex connectivity from week-zero to week 12 between the active and placebo group
Primary	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	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
Secondary	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