Designing a Personalized Diet to Reduce the Risk of Crohn's Disease Onset

Study Overview
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Brief Summary
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The purpose of this trial is to run a pilot study that examines the impact of different dietary components on risk factors such as the Genetic, Environmental, Microbial (GEM) Microbiome Risk Score (GMRS) and fecal calprotectin (FCP), a marker of inflammation in the bowels, and a risk factor for developing Crohn's disease (CD) among first degree relatives (parents, siblings, or offspring) of Crohn's patients. The study will utilize the Western diet and the Mediterranean diet to explore the complex interplay between diet, microbiome, and inflammatory biomarkers to identify specific dietary components that may be beneficial in reducing the risk of developing CD. The study will enroll 30 participants from Mount Sinai Hospital in Toronto.

Detailed Description
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This study is a clinical trial that will occur at Mount Sinai Hospital and healthy first degree relatives of CD patients will be recruited. Participation will occur over 7 weeks with 1 week of consuming the subject's regular diet and 6 weeks of intervention. A total of 30 subjects are expected to be enrolled into this trial. As part of this trial, The study will attempt to modify dietary consumption between the Western Diet (WD) and the Mediterranean Diet (MD) to evaluate participants responses to specific food items key to the WD or MD by monitoring subject's GMRS and FCP. Subjects will be randomized into one of two groups (1:1), in which there will be crossover between the two diets. Stool samples will be collected 3 times a week, a daily questionnaire and a daily consumption diary will be completed through an app. Group 1 will follow the WD for weeks 2 and 3, switch to the MD for weeks 4 and 5, and then back to the WD for weeks 6 and 7. Group 2 will follow the MD for weeks 2 and 3, switch to the WD for weeks 4 and 5, and then back to the MD for weeks 6 and 7. Meal plans developed by the study Dietitian and recipes will be provided for all weeks of the intervention (weeks 2-7). These meal plans will be identical for subjects within the same group. Groceries required to prepare the meals as per the meal plan will be provided to subjects on a weekly basis.

Official Title
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Designing a Personalized Diet to Reduce the Risk of Crohn's Disease Onset

Conditions
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Diet, Healthy, High Risk

Intervention / Treatment
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* Other: Mediteranean to Western to Mediteranean Diet
* Other: Western to Mediteranean to Western Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, asymptomatic first degree relative (child or sibling) of someone with Crohn's disease Have at least 1 bowel movement every other day Exclusion Criteria: Received antibiotic treatment within 3 months of recruitment Unintentional weight loss in the last 3 months more than 15% of baseline weight Have ever been diagnosed with any chronic or recurring gastro-intestinal disease or bowel disease Belly pain occurred more than once per week for longer than three months in the past year Diarrhea (>three times per day) has been occurring for more than three months in the last year Have blood in their stool with most stools Diagnosed with diabetes Diagnosed with Celiac disease Diagnosed with irritable bowel syndrome Diagnosed with inflammatory bowel disease Presents significant symptoms of gastrointestinal disease Pregnant or breastfeeding women Has any serious food allergies Diagnosed with lactose intolerance Unable to stop NSAID or probiotic use during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Western to Mediteranean to Western Diet<br>Weeks 2 and 3 = WD Weeks 4 and 5 = MD Weeks 6 and 7 = WD | Other: Mediteranean to Western to Mediteranean Diet<br>* week 2-3 : Switching between Mediterranean diet and Western diet week 4-5 : Switching between Western diet and Mediterranean diet week 6-7 : Switching between Mediterranean diet and Western diet<br>Other: Western to Mediteranean to Western Diet<br>* week 2-3 : Switching between Western diet and Mediterranean diet week 4-5 : Switching between Mediterranean diet and Western diet week 6-7 : Switching between Western diet and Mediterranean diet<br>|
| Other: Mediteranean to Western to Mediteranean Diet<br>Weeks 2 and 3 = MD Weeks 4 and 5 = WD Weeks 6 and 7 = MD | Other: Mediteranean to Western to Mediteranean Diet<br>* week 2-3 : Switching between Mediterranean diet and Western diet week 4-5 : Switching between Western diet and Mediterranean diet week 6-7 : Switching between Mediterranean diet and Western diet<br>Other: Western to Mediteranean to Western Diet<br>* week 2-3 : Switching between Western diet and Mediterranean diet week 4-5 : Switching between Mediterranean diet and Western diet week 6-7 : Switching between Western diet and Mediterranean diet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Personalized model | Repeated measures of FCP and GMRS will be used to generate a personalized model identifying food items that provide are predicted to have the greatest effect in the GMRS and FCP levels for a given individual | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of FCP levels over time during each intervention | fecal calprotectin will be analyzed from all stool samples collected during the study to provide continual data on any changes in intestinal inflammation | Duration of each diet (2 to 4 weeks) | 
| Modulation of GMRS over time during each intervention | Microbiome data will be collected from all stool samples collected during the study to provide continual data on any changes. This data will be used to calculate the GMRS at each time point. A higher GMRS indicate high risk for Crohn's disease | Duration of each diet (2 to 4 weeks) | 
| Measure of microbial taxa relative abundance over time during each intervention | Microbiome data will be collected from all stool samples collected during the study to provide continual data on any changes in microbial composition | Duration of each diet (2 to 4 weeks) | 
| Ability to maintain a balanced diet as measured by food intake records | Through the submission of the daily food diaries an assessment on the ability to maintain the diet will be reviewed | 6 weeks | 
| Adherence to the interventions | Compliance to the diet will be monitored through an app throughout the study | 6 weeks |