Clinical trial NCT06871748: Effect of a Low FODMAP Diet in IBS and Functional Constipation with Bloating: a Randomized Double-Blind Trial
Official title: Effect of a Low FODMAP Diet in Irritable Bowel Syndrome and Functional Constipation with Bloating: a Randomized Double-Blind Controlled Trial with Microbiota, Intestinal Gas, and Metabolomic Analysis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Irritable Bowel Syndrome (IBS)
Constipation - Functional
Bloating
Keywords: Irritable Bowel Syndrome (IBS)
Functional Constipation
FODMAP
Microbiota
Lead sponsor: Mahidol University
Sponsor class: OTHER
First posted: 2025-03-12
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a randomized, double-blind, controlled trial investigating the effects of a low FODMAP diet compared to a high FODMAP diet in IBS and functional constipation patients with bloating. Participants will be randomly assigned to one of two dietary intervention groups for two weeks. The trial employs block randomization (block size=4). Both participants and study personnel will be blinded to the diet assignment, with identical meal appearances to maintain blinding. Outcomes include clinical symptom improvement, gut microbiota changes, gas production, and metabolomic profiles. Data will be analyzed using chi-square tests, logistic regression, and microbiome diversity metrics. This study aims to provide mechanistic insights and evidence-based dietary recommendations for managing bloating-predominant IBS and functional constipation.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Bloating Severity (VAS)
timeFrame: Baseline to 2 weeks (End of Intervention)
Secondary outcomes:
measure: Reduction in Global IBS Symptoms (IBS-SSS)
timeFrame: Baseline to 2 weeks
measure: Change in Abdominal Pain (VAS)
timeFrame: Baseline to 2 weeks
measure: Change in Stool Frequency and Consistency
timeFrame: Baseline to 2 weeks
measure: Changes in Gut Microbiota Composition
timeFrame: Baseline to 2 weeks
measure: Change in Hydrogen Gas Production (Lactulose Breath Test)
timeFrame: Baseline to 2 weeks
measure: Change in Methane Gas Production (Lactulose Breath Test)
timeFrame: Baseline to 2 weeks
measure: Use of Rescue Medications
timeFrame: Baseline to 2 weeks
measure: Change in Psychological Symptoms (DASS-21)
timeFrame: Baseline to 2 weeks
measure: Change in Quality of Life (IBS-QoL / PAC-QoL)
timeFrame: Baseline to 2 weeks
measure: Patient Satisfaction with Treatment
timeFrame: Baseline to 2 weeks
measure: Change in Patient-Reported Constipation Symptoms (PAC-SYM)
timeFrame: Baseline to 2 weeks
measure: Change in Short-Chain Fatty Acids (SCFAs) Levels
timeFrame: Baseline to 2 weeks
measure: Change in Urine Histamine Levels
timeFrame: Baseline to 2 weeks
measure: Change in Urine Azelaic Acid Levels
timeFrame: Baseline to 2 weeks
measure: Change in Constipation-Specific Quality of Life (PAC-QoL)
timeFrame: Baseline to 2 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Mahidol University Faculty of Medicine Siriraj Hospital
name: Monthira Maneerattanaporn, MD
role: STUDY_DIRECTOR
affiliation: Mahidol University Faculty of Medicine Siriraj Hospital
name: Tanawat Geeratragool, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mahidol University Faculty of Medicine Siriraj Hospital
name: Somchai Leelakusolvong, MD
role: STUDY_CHAIR
References:
citation: Drossman DA, Tack J. Rome Foundation Clinical Diagnostic Criteria for Disorders of Gut-Brain Interaction. Gastroenterology. 2022 Mar;162(3):675-679. doi: 10.1053/j.gastro.2021.11.019. Epub 2021 Nov 19. No abstract available.
citation: Camilleri M. Diagnosis and Treatment of Irritable Bowel Syndrome: A Review. JAMA. 2021 Mar 2;325(9):865-877. doi: 10.1001/jama.2020.22532.
citation: Andrews CN, Sidani S, Marshall JK. Clinical Management of the Microbiome in Irritable Bowel Syndrome. J Can Assoc Gastroenterol. 2020 Jan 4;4(1):36-43. doi: 10.1093/jcag/gwz037. eCollection 2021 Feb.
citation: Varney J, Barrett J, Scarlata K, Catsos P, Gibson PR, Muir JG. FODMAPs: food composition, defining cutoff values and international application. J Gastroenterol Hepatol. 2017 Mar;32 Suppl 1:53-61. doi: 10.1111/jgh.13698.
citation: Muir JG, Shepherd SJ, Rosella O, Rose R, Barrett JS, Gibson PR. Fructan and free fructose content of common Australian vegetables and fruit. J Agric Food Chem. 2007 Aug 8;55(16):6619-27. doi: 10.1021/jf070623x. Epub 2007 Jul 11.