Efficacy of Low-FODMAPs Dietary Therapy for Irritable Bowel Syndrome in China

Efficacy of Low-FODMAPs Dietary Therapy Versus Traditional Dietary Advice for Diarrhea-predominant Irritable Bowel Syndrome in China - A Prospective Randomized Controlled Trial

The primary aim of our study is to carry out a randomized trial to evaluate the efficacy of low-FODMAPs dietary therapy compared to conventional therapy for IBS patients recruited from tertiary hospitals in China. Secondary aims of this research include an analysis of clinical, physiological and microbiological factors that may predict IBS patient response to this dietary intervention.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome; Diet Modification
• Intervention / Treatment: Dietary supplement: low-FODMAPs diet; Dietary supplement: Traditional dietary advice

Detailed Description

Visit 1：Enrollment & Screening & Run-in period Patients who meet the inclusion criteria will be asked to complete IBS Baseline Assessment Questionnaires according to Rome III.Subjects that meet the criteria will receive verbal and written information about the study and provide written informed consent. After meeting with the dietitian and physician who will provide instructions, they will be asked to complete Combined Nutrient and Lactulose Breath Test.[16] Additionally, a baseline food and symptom diary will be completed in a (minimum) 14 day run-in period after breath test (the first 48hr after the breath test will not be included in this analysis). This diary record prior to the intervention will document baseline symptom severity and capture the habitual diet of IBS patients.

Visit 2: Randomization & Intervention. After the run-in period, patients will come back to the clinic to receive dietary instruction ahead of starting the intervention. At the same visit subjects will provide fresh stool for fermentation analysis (including short chain fatty acids and pressure detection) and blood for cytokines analysis. Subjects will then be randomly assigned to either low FODMAP diet (LFD) group or traditional dietary advice for IBS (TDA) group by computer-generated random number table. Participants will receive food instructions by a dietitian, according to their assignment. Throughout the study, only the dietitian will be aware of the assignment of the intervention given. Both diet therapy will last for 3 weeks, and all the subjects are instructed to complete daily food and symptom diary through a provided booklet. IBS Symptoms Severity Scores (IBS-SSS) is evaluated every week and the dietitian who is not aware of the allocation will make a telephone follow-up to assess patient adherence.

Visit 3: End of treatment & Follow-up. After 3 weeks of intervention, the participants will attend a follow-up appointment and complete the IBS Post-Intervention Assessment Questionnaires. Fresh stools and blood are recollected at this visit to evaluate for possible change in gut microbiota and cytokines after diet intervention.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhe Jiang
    • Hangzhou, Zhe Jiang, China, 310016
      • Sir Run Run Shaw Hospital , College of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-65 years old.
• Meet Rome Rome III criteria for IBS-D.
• All these patients should have no abnormality in blood, stool analysis or colonoscopy within the previous 2 years.
• No GI alarm symptoms.

Exclusion Criteria:

• Presence of a severe cardiac, hepatic, nephritic, neurologic disease.
• Presence of mental disorders caused by schizophrenia, organic brain disorder or physical disease.
• Other comorbid medical conditions (eg.unstable diabetes, unstable thyroid disease).
• Previous abdominal surgery except appendectomy or hysterectomy.
• Pregnant or lactating women.
• Use of probiotics, prebiotics, lactulose, antidiarrheal agents or bowel preparation within the 4 weeks prior to the study.
• Participation in any other form of dietary therapy within the 4 weeks prior to the study.
• Difficulties in communication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low-FODMAPs diet; The low-FODMAPs diet(LFD) aims to keep oligosaccharides, fructose in excess of glucose, and polyol content at less than 0.5 g each per serving based on previously published data. low-FODMAPs diet therapy for 3 weeks	Dietary supplement: low-FODMAPs diet; The low-FODMAPs diet(LFD) aims to keep oligosaccharides, fructose in excess of glucose, and polyol content at less than 0.5 g each per serving based on previously published data. low-FODMAPs diet therapy for 3 weeks
Placebo Comparator: Traditional dietary advice; Traditional dietary advice (TDA) will focus more on how and when to eat rather than on what foods to ingest . Patients will be instructed to regularly eat, never too much or too little, never to be hungry or too full; to eat in peace and to chew thoroughly; reduce intake of fatty, spicy food, fiber, coffee and alcohol during the intervention period Traditional dietary advice for 3 weeks	Dietary supplement: Traditional dietary advice; Traditional dietary advice(TDA) will focus more on how and when to eat rather than on what foods to ingest . Patients will be instructed to regularly eat, never too much or too little, never to be hungry or too full; to eat in peace and to chew thoroughly; reduce intake of fatty, spicy food, fiber, coffee and alcohol during the intervention period traditional dietary advice for 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare response to diet intervention between different groups.	Primary endpoint will be response to 3-week of diet intervention defined by shows >50 point reduction in IBS-SSS between baseline and post-intervention scores. The proportion of responders who met primary endpoint in each group will be compared.	three weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in abdominal pain between different groups.	Compare improvement about abdominal pain during 3-week intervention period between different groups according to Food and Drug Administration (FDA) individual composite end point (≥30% reduction in mean daily abdominal pain score).	Three weeks
Improvement in stool consistency between different groups.	Compare improvement about stool consistency during 3-week intervention period between different groups according to Food and Drug Administration (FDA) individual composite end point (a decrease in mean daily Bristol Stool Score (BSS) value of ≥1 compared with baseline for any 2 weeks of the intervention period).	Three weeks
Compare changes from baseline in abdominal pain score between different groups.	Compare group changes from baseline in abdominal pain score，averaged over each treatment week for total three weeks.	Every week, last for three weeks
Compare changes from baseline in abdominal frequency between different groups.	Compare group changes from baseline in abdominal frequency, averaged over each treatment week for total three weeks.	Every week, last for three weeks
Compare changes from baseline in bloating score between different groups.	Compare group changes from baseline in bloating score, averaged over each treatment week for total three weeks.	Every week, last for three weeks
Compare changes from baseline in excessive wind score between different groups.	Compare group changes from baseline in excessive wind score, averaged over each treatment week for total three weeks.	Every week, last for three weeks
Compare changes from baseline in stool consistency between different groups.	Compare group changes from baseline in stool consistency as measured by BSS, averaged over each treatment week for total three weeks..	Every week, last for three weeks
Compare changes from baseline in stool frequency between different groups.	Compare group changes from baseline in stool frequency, averaged over each treatment week for total three weeks.	Every week, last for three weeks
Compare changes from baseline in urgency score between different groups.	Compare group changes from baseline in urgency score, averaged over each treatment week for total three weeks.	Every week, last for three weeks
Compare changes from baseline in incomplete defecation score between different groups.	Compare group changes from baseline in incomplete defecation score, averaged over each treatment week for total three weeks.	Every week, last for three weeks
Compare changes from baseline in quality of life between different groups.	Compare group changes between baseline and post-intervention(3 weeks later) about quality of life evaluated by IBS-QOL.	Three weeks
Compare changes from baseline in mental health between different groups.	Compare group changes between baseline and post-intervention(3 weeks later) about mental health evaluated by GAD-7 and PHQ-9.	Three weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare group difference about stool fermentation production before and after intervention.	Compare group difference about stool fermentation production- short chain fatty acids, before and after 3-week intervention .	Three weeks
Compare group difference about fecal microbial α- diversity displayed by Shannon index before and after intervention.	Fresh feces will be collected from patients at baseline and the end of the intervention (three weeks intervention), and the fecal DNA will be extracted by MOBIO PowerSoil DNA Isolation Kit according to the instructions. The 16S rRNA sequencing will be performed from the extracted DNA. Within-community diversity (α- diversity displayed by Shannon index) will be further calculated according to the sequencing results.	Three weeks
Compare group difference about fecal microbial β- diversity displayed by Principal Component Analysis (PCA) before and after intervention.	Fresh feces will be collected from patients at baseline and the end of the intervention (three weeks intervention), and the fecal DNA will be extracted by MOBIO PowerSoil DNA Isolation Kit according to the instructions. The 16S rRNA sequencing will be performed from the extracted DNA. Between-community diversity (β- diversity displayed by Principal Component Analysis (PCA)) will be further calculated according to the sequencing results.	Three weeks
Compare group difference about fecal microbial communities before and after intervention.	Fresh feces will be collected from patients at baseline and the end of the intervention (three weeks intervention), and the fecal DNA will be extracted by MOBIO PowerSoil DNA Isolation Kit according to the instructions. The 16S rRNA sequencing will be performed from the extracted DNA. LEfSe (linear discriminant analysis coupled with effect size measurements) will be further calculated according to the sequencing results.	Three weeks
Compare stool microbial α- diversity displayed by Shannon between responders and non-responders	Fresh feces collected from responders and nonresponders to interventions at baseline will be analyzed by 16S rRNA sequencing. Within-community diversity (α- diversity displayed by Shannon index) will be further calculated according to the sequencing results.	Baseline (0 week)
Compare stool microbial β- diversity displayed by Principal Component Analysis (PCA) between responders and non-responders	Fresh feces collected from responders and nonresponders to interventions at baseline will be analyzed by 16S rRNA sequencing. Between-community diversity (β- diversity displayed by Principal Component Analysis (PCA)) will be further calculated according to the sequencing results.	Baseline (0 week)
Compare stool microbial communities between responders and non-responders	Fresh feces collected from responders and nonresponders to interventions at baseline will be analyzed by 16S rRNA sequencing. LEfSe (linear discriminant analysis coupled with effect size measurements) will be further calculated according to the sequencing results.	Baseline (0 week)
Compare stool fermentation production between responders and non-responders	Compare stool fermentation production- short chain fatty acids, between responders and non-responders	Baseline (0 week)
Compare IBS symptom severity between responders and non-responders	Compare IBS symptom severity (measured by IBS symptom severity scale(IBS-SSS)) between responders and non-responders	Baseline (0 week)

Collaborators and Investigators

• Sponsor: Sir Run Run Shaw Hospital
• Collaborators: University of Michigan; Klinik Arlesheim; Zhejiang Academy of Agricultural Sciences
• Investigators: Principal Investigator: Yawen Zhang, MM, Sir Run Run Shaw Hospital; Principal Investigator: Lijun Feng, Sir Run Run Shaw Hospital

Publications and helpful links

General Publications

• Zhang Y, Feng L, Wang X, Fox M, Luo L, Du L, Chen B, Chen X, He H, Zhu S, Hu Z, Chen S, Long Y, Zhu Y, Xu L, Deng Y, Misselwitz B, Lang BM, Yilmaz B, Kim JJ, Owyang C, Dai N. Low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet compared with traditional dietary advice for diarrhea-predominant irritable bowel syndrome: a parallel-group, randomized controlled trial with analysis of clinical and microbiological factors associated with patient outcomes. Am J Clin Nutr. 2021 Jun 1;113(6):1531-1545. doi: 10.1093/ajcn/nqab005.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2017
• Primary Completion (Actual): May 31, 2018
• Study Completion (Actual): May 31, 2019

Study Registration Dates

• First Submitted: July 20, 2017
• First Submitted That Met QC Criteria: October 1, 2017
• First Posted (Actual): October 6, 2017

Study Record Updates

• Last Update Posted (Actual): September 12, 2019
• Last Update Submitted That Met QC Criteria: September 11, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Irritable Bowel Syndrome; Breath test; low-FODMAP; stool fermentation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome
• Other Study ID Numbers: 20170116-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No