A Dietary Intervention Study on the Microbiome in Crohn's Disease Patients

Study Overview
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Brief Summary
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This protocol is designed to compare the effectiveness of a soy-based diet or identical diet without soy given to patients with Crohn's disease (CD) in remission, patients with active CD, or healthy controls. The assigned diet will be compared to participant 'baseline' (pre-diet) in terms of its ability to change the gut bacteria and fecal butyrate, an important short-chain fatty acid (SCFA) that limits bowel inflammation, a characteristic of this debilitating disease.

Detailed Description
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The inflammatory bowel disease (IBD) subtype, Crohn's disease (CD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract. Although the precise etiology of IBD is not known, evidence suggests that environmental factors, including diet, contribute to its pathogenesis. A soy-based diet has been demonstrated to have numerous health benefits. This single-center open-label study will compare the effectiveness of a soy-based diet or an identical diet without soy to change the gut microbiota composition and fecal butyrate concentration to that of baseline (pre-diet) in patients with CD (remission or active disease) and healthy control subjects without CD. Participants will follow either a soy-based diet or an identical diet without soy to which they will be randomized for 7 days. No data collection or other study procedures will take place until the potential participant provides written informed consent to participate in the research study. The informed consent, screening, enrollment, and baseline data collection which make up visit 1 can occur on the same day or be completed across several days.

Official Title
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A Single-center Open-label Study to Determine the Effect of Diet on Microbiome Signatures in Crohn's Disease Patients

Conditions
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Crohn Disease

Intervention / Treatment
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* Other: Soy based diet
* Other: Non-soy based diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CD subjects: Documented diagnosis of Crohn's disease. Control subjects: no documented diagnosis of CD. CD subjects: Harvey Bradshaw Index (HBI) score <4 ('CD remission'), or with HBI score >8 ('CD moderate disease') Capable of providing consent to participate Access to technology that permits the daily completion of study related activities Able to receive and have an adult sign for food shipments delivered to a work or home environment. Negative pregnancy test at screening visit in females of childbearing potential Able to take oral nutrition and medication intake for 3 months prior to and at time of study enrolment. 'CD remission' subjects: No change in 'IBD related' medications within 8 weeks prior to normally scheduled appointment with treating gastroenterologist (pre-screening): biologics, immunosuppressants, corticosteroids. Exclusion Criteria: Short bowel syndrome. Hospitalized patients Body mass Index <19 kg/m or ≥35. Known clinically significant liver/gallbladder/pancreatic disease/dysfunction Individuals who lack consent capacity, including the mentally ill, prisoners, cognitively impaired participants, dementia patients. Uncontrolled Diabetes Type I type II Known drug abuse. Known parasitic disease of the digestive system. symptomatic intestinal stricture. Presence of an ostomy. Known concurrent malignancy. Other conditions that would be a contraindication to and of the study diets (e.g. Soy, peanut, wheat, gluten allergy.) or preclude the participant from completing the study Start of new 'IBD related' medications within 8 weeks prior to enrollment: biologics, immunosuppressants, corticosteroids. Documented C difficile colitis within four weeks of screening Well-founded doubt about the patient's cooperation. Existing pregnancy or lactation. Current participation in another diet intervention, simultaneous participation in another clinical trial, or participation in any other dietary intervention trial within the last 30 days. History of <3 natural bowel movements per week. Unable to access to technology that permits the daily completion of study related activities. Currently consuming a soy-based diet

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is an open label single center study to compare the effect of a soy-based diet or an identical diet without soy on the composition and metabolite production of gut bacteria in Crohn's disease (CD) patients in remission or active disease, and in healthy controls. Crohn's subjects will be pre-screened by the treating gastroenterologist for eligibility criteria during their normally scheduled appointment. The treating gastroenterologist will ask suitable patients whether they are interested in participating in the described dietary intervention study during the patient appointment. Initial verbal consent will be obtained by the treating gastroenterologist. Healthy controls will be recruited in the same manner, as well as via a hospital flyer advertisement. Subjects will then be contacted by the study investigator to schedule a screening visit (visit 1) and if study eligibility is confirmed, and informed consent provided, enrolled into the study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Soy-based diet<br>Participants will be randomized to follow a soy-based diet for 7 days. The diet will be preceded by a 12-hr overnight fast. | Other: Soy based diet<br>* The diet will be based on the detailed descriptions according to the American Heart Association, US Food and Drug Administration (FDA), and the Soyfoods Association of North America Website, which all promote soy products as having beneficial nutrient profiles with a daily consumption of 25 grams or more of soy protein (average serving = 6.25 grams), upper limit of 50g.<br>|
| Active Comparator: Regular diet<br>Participants will be randomized to follow a diet without soy for 7 days. The diet will be preceded by a 12-hr overnight fast. | Other: Non-soy based diet<br>* Diet of identical composition to the soy diet with the exception of soy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maintenance of Symptomatic Remission, without worsening of any existing disease activity during study period | The primary aim will focus on maintaining quiescent disease status, without worsening of any existing disease activity of the patient with Crohn's disease (CD) before/after diet intervention. This will be measured at the enrollment and end of study visits using the Crohn's Disease Activity Index (CDAI). Fecal myleoperoxidase will also be assessed. | measured after the 7-day diet intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes to Functional Composition of Gut Microbiota | Secondary outcome will focus on changes to the functional composition of fecal gut microbiota, including bacterial butryate production after the diet intervention. | measured after the 7-day diet intervention | 
| Proportion of subjects who continue diet following completion of study | To assess the proportion of patients who intend to continue the study diets when prepared food is no longer provided without cost, and the reasons for discontinuation of either diet (compared to resuming usual food habits). | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diet, inflammatory bowel disease, gut microbiome