Effect of a Probiotic Mixture on the Gut Microbiome and Fatigue in Patients With Quiescent Inflammatory Bowel Disease

Study Overview
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Brief Summary
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The study is proposed as a single-site randomized double-blind placebo-controlled trial requiring 4 study visits, where two of the visits are combined with their appointment for routine clinical care. The study population will consist of patients with quiescent CD and UC and IBD-unspecified recruited from the Massachusetts General Hospital Crohn's and Colitis center. All eligible subjects will have a confirmed diagnosis of CD, UC, or IBD-unspecified according to accepted clinical, endoscopic, radiologic, and histologic criteria. Eligible patients will be contacted at the time of their routinely scheduled office visit and consented for the study. Self-report and review of medical records will be used to obtain detailed information regarding their disease on an intake questionnaire completed by a research study coordinator. The study is proposed as a 12-week double-blind randomized controlled trial of the probiotic supplement compared to placebo. We propose to examine the effect of a specific probiotic supplement on the changes in the gut microbiome, serum metabolomic profile, and fatigue symptoms in patients with quiescent IBD. Within 2 weeks of screening, eligible patients will be invited to visit MGH for a baseline visit. The patient will receive either the probiotic supplement or placebo for 4 weeks. The first follow up visit will be at week 4 to check for adverse events on study treatment, to check accountability of probiotics/placebo, and to complete the set of questionnaires. Also, subjects will receive probiotic/placebo samples for the remaining 8 weeks of treatment. At week 8, subjects will receive a phone call from a study research coordinator to check in with probiotics/placebo intake for treatment compliance and accountability records, and to complete the set of questionnaires ascertaining subjective symptoms. Last study visit will be at week 12 which is often combined with a regular office appointment. Subject will provide serum blood and stool sample, as well as complete the set of questionnaires.

Official Title
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Effect of Dietary Therapy With a Probiotic Mixture on the Gut Microbiome and Fatigue Symptoms in Patients With Quiescent Inflammatory Bowel Disease - A Clinical Trial

Conditions
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Inflammatory Bowel Diseases, Crohn Disease, Ulcerative Colitis

Intervention / Treatment
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* Dietary Supplement: Probiotic Mixture
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years Confirmed CD or UC or IBD-unspecified diagnosed according to standard criteria Quiescent disease defined as Harvey Bradshaw index < 4 at baseline (week 0) or SCCAI < 2 Persistent ongoing fatigue symptoms Endoscopic or radiologic remission within 12 months of screening Washout of non-study probiotic supplements for at least 4 weeks prior to screening. Exclusion Criteria: Patients with clinical or endoscopically active inflammatory bowel disease Significant non-IBD comorbidity contributing to the fatigue (such as active cancer). Untreated severe depression or anxiety Known sleep disorders without adequate treatment, Presence of J-pouch or a stoma Ongoing use of other non-study probiotics Women who are pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Probiotic Mixture<br>Participants who are meeting the inclusion criteria will be randomized to either the probiotic mixture or an identical placebo. The probiotics sachets will be taken twice a day for 12 weeks. | Dietary Supplement: Probiotic Mixture<br>* The probiotic supplement contains 8 different strains of bacteria and participants will be dosed in two dosages per a total of 40 billion bacteria daily.<br>|
| Placebo Comparator: Placebo<br>Participants who are meeting the inclusion criteria will be randomized to either the probiotic mixture or an identical placebo The identical placebo sachets will be taken twice a day for 12 weeks. | Dietary Supplement: Placebo<br>* A placebo which is identical to the probiotic mixture. Participants will be dosed in two dosages daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in gut microbiome | Change in fecal microbiome pattern assessed using 16sRNA sequencing. | Week 12 | 
| Change in serum inflammatory cytokines levels | Change in inflammatory cytokines will be performed using the Biosciences Cytometric Bead Array kits. | Week 12 | 
| Change in metabolomic profiles | Change in metabolic profiling will be performed on serum samples using established targeted quantitative and semi-quantitative gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) methods | Week 12 | 
| Change in fatigue symptoms | Reduction of fatigue symptoms which will be assessed using FACIT-F questionnaire. FACIT-F score of >43 at week 4 or week 12 | Week 4 and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Microbiome, Fatigue, Probiotics