Effect of a Low FODMAP Diet in IBS and Functional Constipation with Bloating: a Randomized Double-Blind Trial

Not Applicable

Not yet recruiting

• Conditions: Irritable Bowel Syndrome (IBS); Constipation - Functional; Bloating

• Registration Number: NCT06871748
• Lead Sponsor: Mahidol University

Brief Summary

This clinical study aims to evaluate the effects of a low FODMAP diet compared to a high FODMAP diet in patients with Irritable Bowel Syndrome (IBS) and Functional Constipation (FC) with predominant bloating. The study is a randomized, double-blind, controlled trial designed to assess whether a diet low in fermentable carbohydrates can improve bloating symptoms, gut microbiota composition, intestinal gas production, and metabolic outputs.

Patients meeting the Rome IV criteria for IBS or FC with persistent bloating will be enrolled and randomly assigned to receive either a low or high FODMAP diet for two weeks. Meals will be standardized to control FODMAPs composition, ensuring that FODMAP content is the primary variable.

The primary endpoint is the proportion of participants with a ≥30% reduction in bloating severity, measured using the Visual Analog Scale (VAS). Secondary outcomes include changes in global IBS symptoms, abdominal pain, bowel movements, stool consistency, microbiota diversity, hydrogen/methane gas production, and metabolomic profiles.

This study will contribute to the growing body of evidence supporting dietary management in disorders of gut-brain interaction (DGBI), particularly in bloating-predominant IBS and FC, and will provide insights into the mechanisms linking diet, gut microbiota, and symptom improvement.

Detailed Description

Irritable Bowel Syndrome (IBS) and Functional Constipation (FC) are chronic Disorders of Gut-Brain Interaction (DGBI) characterized by altered motility, visceral hypersensitivity, dysbiosis, and central nervous system processing abnormalities. Bloating is a challenging and distressing symptom that often persists despite standard pharmacological treatments.

The low FODMAP diet has been widely studied as a dietary approach to alleviate IBS symptoms. FODMAPs (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) are poorly absorbed short-chain carbohydrates that increase osmolarity, promote intestinal gas production, and alter gut microbiota, leading to bloating and discomfort. Although studies support the effectiveness of the low FODMAP diet, existing research lacks controlled, blinded trials assessing its impact on bloating-specific symptoms and related physiological markers.

This study addresses these gaps by using a double-blind, controlled design with rigorously standardized meals containing well-defined FODMAP content. It will assess clinical outcomes, gut microbiota composition, gas production, and metabolomic changes to elucidate the mechanisms underlying the diet's effects.

Study Design This is a randomized, double-blind, controlled trial conducted at a single center. Participants will be assigned to receive either a low FODMAP or a high FODMAP diet for two weeks.

Participants:

Adults ≥18 years diagnosed with IBS or FC with persistent bloating based on Rome IV criteria.

Intervention:

Standardized meal plans containing either low FODMAP or high FODMAP content.

Randomization:

Computer-generated block randomization (block of 4)

Blinding:

Investigators, study staff, and participants will remain blinded to the dietary allocation.

Primary Outcome:

≥30% reduction in bloating severity on the VAS scale.

Secondary Outcomes:

Changes in global IBS symptoms (IBS-SSS) or constipation symptoms (PAC-Sym) Abdominal pain (VAS) stool frequency, and consistency (Bristol Stool Form Scale). Gut microbiota diversity and composition (16S rRNA sequencing). Intestinal gas production (hydrogen/methane breath test). Metabolomic analysis (short-chain fatty acids, urine histamine, azelaic acid). Use of rescue medications for symptom relief.

Study Procedures

Baseline Assessment:

Demographic data, medical history, and dietary habits (7-day food diary). Baseline bloating severity, stool consistency, and quality of life (IBS-QoL, PAC-QoL).

Microbiota, breath test, and metabolomic sampling.

Intervention Phase (2 Weeks):

Participants consume standardized low or high FODMAP meals (3 main meals + 1 snack/day).

Daily recording of symptoms, bowel movements, and use of rescue medications.

Follow-up Assessments:

Week 1: Phone follow-up to assess adherence and symptom progression. Week 2: Final clinical and laboratory assessments (identical to baseline). Data collection for statistical analysis comparing treatment effects.

Statistical Analysis Primary endpoint (bloating reduction) analyzed using Chi-square/Fisher's exact test.

Secondary outcomes analyzed with paired t-tests, Mann-Whitney U tests, and logistic regression.

Microbiota diversity assessed using Shannon index, beta diversity, and PERMANOVA testing.

Significance and Impact This study will provide high-quality evidence on the effectiveness of the low FODMAP diet for bloating-predominant IBS and FC, addressing critical knowledge gaps. By integrating clinical, microbiota, and metabolomic data, it will enhance understanding of diet-microbiota interactions and their role in symptom modulation.

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-28
• Study First Submitted QC: 2025-03-06
• Last Update Submitted: 2025-03-06
• Study First Posted: 2025-03-12
• Last Update Posted: 2025-03-12
• Study Start: 2025-03-15
• Primary Completion: 2026-03-15
• Study Completion: 2026-07-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

• Age ≥18 years
• Diagnosed with Irritable Bowel Syndrome (IBS) or Functional Constipation (FC) based on Rome IV criteria
• Persistent bloating affecting daily life, with a bloating VAS score ≥4
• Stable bowel habits with Bristol Stool Form Scale (BSFS) type 3-5
• History of prior treatment with antispasmodics and/or prokinetics (allowed if dose remains stable)
• Able to comply with dietary intervention and study procedures

Exclusion Criteria

• Prior gastrointestinal surgery (except appendectomy or cholecystectomy)
• Use of antibiotics, proton pump inhibitors (PPIs), probiotics, NSAIDs, lactulose, or metformin within the past 4 weeks
• Presence of systemic diseases affecting gut microbiota (e.g., liver cirrhosis, uncontrolled diabetes, end-stage renal disease, obesity, cancer, psychiatric disorders)
• Inability to consume study meals or follow dietary restrictions

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in Bloating Severity (VAS)	Baseline to 2 weeks (End of Intervention)	The primary outcome is the change in bloating severity, measured using the Visual Analog Scale (VAS). The VAS score ranges from 0 (no bloating) to 10 (severe bloating), with higher scores indicating worse bloating symptoms. Participants will record daily bloating scores throughout the intervention period. The proportion of participants achieving a ≥30% decrease in bloating severity from baseline will be analyzed.

Secondary Outcome Measures

Name	Time	Method
Reduction in Global IBS Symptoms (IBS-SSS)	Baseline to 2 weeks	Change in IBS Symptom Severity Score (IBS-SSS) from baseline, assessing overall IBS symptom burden, abdominal pain, bloating, and bowel habit changes. The IBS-SSS scale ranges from 0 to 500, with higher scores indicating more severe IBS symptoms.
Change in Abdominal Pain (VAS)	Baseline to 2 weeks	Change in abdominal pain severity, measured using the Visual Analog Scale (VAS). The VAS scale ranges from 0 (no pain) to 10 (severe pain), with higher scores indicating worse pain severity. Participants will record daily pain scores, and the difference between baseline and post-intervention scores will be analyzed.
Change in Stool Frequency and Consistency	Baseline to 2 weeks	Change in bowel movement frequency and stool consistency, assessed using the Bristol Stool Form Scale (BSFS).; Stool frequency will be recorded as the number of bowel movements per day.; Stool consistency will be graded using the BSFS scale (1-7): 1-2: Hard stools (constipation) 3-4: Normal stools 5-7: Loose stools (diarrhea) Higher BSFS scores indicate looser stool consistency. The difference between baseline and post-intervention values will be analyzed.
Changes in Gut Microbiota Composition	Baseline to 2 weeks	Alterations in gut microbiota diversity and abundance (16S rRNA sequencing).
Change in Hydrogen Gas Production (Lactulose Breath Test)	Baseline to 2 weeks	Change in exhaled hydrogen (H₂) levels, measured via lactulose breath test in parts per million (ppm). Higher hydrogen levels indicate increased fermentation by colonic microbiota.
Change in Methane Gas Production (Lactulose Breath Test)	Baseline to 2 weeks	Change in exhaled methane (CH₄) levels, measured via lactulose breath test in parts per million (ppm). Elevated methane levels are associated with slow colonic transit and constipation.
Use of Rescue Medications	Baseline to 2 weeks	Frequency and dosage of antispasmodics, prokinetics, or laxatives used for symptom relief.
Change in Psychological Symptoms (DASS-21)	Baseline to 2 weeks	Change in Depression, Anxiety, and Stress Scores (DASS-21), a validated self-reported scale measuring psychological distress. The DASS-21 consists of three subscales: Depression (0-21) Anxiety (0-21) Stress (0-21) Each subscale score ranges from 0 (normal) to 21 (severe symptoms), with higher scores indicating greater psychological distress. The total score is calculated by summing individual subscale scores.
Change in Quality of Life (IBS-QoL / PAC-QoL)	Baseline to 2 weeks	Change in IBS-specific Quality of Life (IBS-QoL) score, which assesses the impact of IBS on daily activities, emotional well-being, and social functioning.; The IBS-QoL score ranges from 0 to 100, with higher scores indicating better quality of life.
Patient Satisfaction with Treatment	Baseline to 2 weeks	Overall treatment satisfaction, measured using a Visual Analog Scale (VAS) ranging from 0 to 10: 0 = Completely Dissatisfied 10 = Completely Satisfied Higher scores indicate greater satisfaction with treatment. The difference between baseline and post-intervention scores will be analyzed.
Change in Patient-Reported Constipation Symptoms (PAC-SYM)	Baseline to 2 weeks	Change in Patient Assessment of Constipation-Symptoms (PAC-SYM) score, evaluating constipation-related symptoms, including stool consistency, discomfort, and straining. The PAC-SYM scale ranges from 0 to 48, with higher scores indicating worse constipation symptoms.
Change in Short-Chain Fatty Acids (SCFAs) Levels	Baseline to 2 weeks	Change in fecal short-chain fatty acids (SCFAs), including acetic acid, propionic acid, and butyric acid, measured in μmol/g stool. Higher SCFA levels indicate greater microbial fermentation activity.
Change in Urine Histamine Levels	Baseline to 2 weeks	Change in urine histamine concentration, measured in μg/mL urine, assessing histamine metabolism related to gut inflammation and microbiota activity. Higher levels indicate increased histamine production.
Change in Constipation-Specific Quality of Life (PAC-QoL)	Baseline to 2 weeks	Change in Patient Assessment of Constipation-Quality of Life (PAC-QoL) score, evaluating the impact of constipation on daily life, physical discomfort, psychological well-being, and social aspects.; The PAC-QoL score ranges from 0 to 100, with higher scores indicating better quality of life.
Change in Urine Azelaic Acid Levels	Baseline to 2 weeks	Change in urine azelaic acid concentration, measured in μg/mL urine, assessing microbial metabolic changes associated with gut dysbiosis and inflammation. Higher levels indicate altered microbial metabolism.