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

Sponsor

Sir Run Run Shaw Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT03304041

Collaborator

Zhejiang Academy of Agricultural Sciences (Other), University of Michigan (Other), Klinik Arlesheim (Other)

108

Enrollment

Location

Arms

19.6

Actual Duration (Months)

5.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Irritable Bowel Syndrome Diet Modification	Dietary Supplement: low-FODMAPs diet Dietary Supplement: Traditional dietary advice	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

108 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 10, 2017

Actual Primary Completion Date :

May 31, 2018

Actual Study Completion Date :

May 31, 2019

Arms and Interventions

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

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

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

Outcome Measures

Primary Outcome Measures

Compare response to diet intervention between different groups. [three weeks]
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.

Secondary Outcome Measures

Improvement in abdominal pain between different groups. [Three weeks]
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).
Improvement in stool consistency between different groups. [Three weeks]
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).
Compare changes from baseline in abdominal pain score between different groups. [Every week, last for three weeks]
Compare group changes from baseline in abdominal pain score，averaged over each treatment week for total three weeks.
Compare changes from baseline in abdominal frequency between different groups. [Every week, last for three weeks]
Compare group changes from baseline in abdominal frequency, averaged over each treatment week for total three weeks.
Compare changes from baseline in bloating score between different groups. [Every week, last for three weeks]
Compare group changes from baseline in bloating score, averaged over each treatment week for total three weeks.
Compare changes from baseline in excessive wind score between different groups. [Every week, last for three weeks]
Compare group changes from baseline in excessive wind score, averaged over each treatment week for total three weeks.
Compare changes from baseline in stool consistency between different groups. [Every week, last for three weeks]
Compare group changes from baseline in stool consistency as measured by BSS, averaged over each treatment week for total three weeks..
Compare changes from baseline in stool frequency between different groups. [Every week, last for three weeks]
Compare group changes from baseline in stool frequency, averaged over each treatment week for total three weeks.
Compare changes from baseline in urgency score between different groups. [Every week, last for three weeks]
Compare group changes from baseline in urgency score, averaged over each treatment week for total three weeks.
Compare changes from baseline in incomplete defecation score between different groups. [Every week, last for three weeks]
Compare group changes from baseline in incomplete defecation score, averaged over each treatment week for total three weeks.
Compare changes from baseline in quality of life between different groups. [Three weeks]
Compare group changes between baseline and post-intervention(3 weeks later) about quality of life evaluated by IBS-QOL.
Compare changes from baseline in mental health between different groups. [Three weeks]
Compare group changes between baseline and post-intervention(3 weeks later) about mental health evaluated by GAD-7 and PHQ-9.

Other Outcome Measures

Compare group difference about stool fermentation production before and after intervention. [Three weeks]
Compare group difference about stool fermentation production- short chain fatty acids, before and after 3-week intervention .
Compare group difference about fecal microbial α- diversity displayed by Shannon index before and after intervention. [Three weeks]
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.
Compare group difference about fecal microbial β- diversity displayed by Principal Component Analysis (PCA) before and after intervention. [Three weeks]
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.
Compare group difference about fecal microbial communities before and after intervention. [Three weeks]
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.
Compare stool microbial α- diversity displayed by Shannon between responders and non-responders [Baseline (0 week)]
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.
Compare stool microbial β- diversity displayed by Principal Component Analysis (PCA) between responders and non-responders [Baseline (0 week)]
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.
Compare stool microbial communities between responders and non-responders [Baseline (0 week)]
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.
Compare stool fermentation production between responders and non-responders [Baseline (0 week)]
Compare stool fermentation production- short chain fatty acids, between responders and non-responders
Compare IBS symptom severity between responders and non-responders [Baseline (0 week)]
Compare IBS symptom severity (measured by IBS symptom severity scale(IBS-SSS)) between responders and non-responders

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.