Diet as Essential Therapy (DIET) for Inflammatory Bowel Disease

Study Overview
=================
Brief Summary
-----------------
Recent data suggest that diet in inflammatory bowel disease (IBD) may lead to both symptom control and disease remission. Historically certain diets have been recommended for patients with Crohn's disease during exacerbations despite lack of data supporting efficacy. The investigators propose to evaluate two such diets by randomizing 32 subjects with mildly to moderately active Crohn's disease to one of two diets that differ in the amount and type of carbohydrates and fiber. Subjects will remain on the diet for 8 weeks and will be evaluated for changes from baseline in inflammatory biomarkers, symptomatic disease activity, and the microbiome.

Detailed Description
-----------------
Subjects will be randomized in a 1:1 ratio to receive one of two diets that are thought to be beneficial for Crohn's disease for a period of 8 weeks. Initial evaluation will include a clinic visit with physical exam, medication review, supplemental documentation, and labs. Patients will be asked about their food allergies and intolerances against a master list of all ingredients used in both diets. Patients will then be provided with instructions on how to record their baseline dietary intake for two weeks prior to the intervention diet. At day 0 patients will begin their study diet. All study meals will be provided to the subject and an approved snack list for the randomized diet will be provided in a sealed envelope with their first week of meals. At the conclusion of intervention patients will be asked to resume their previous diet for 4 weeks and record their dietary intake. Stool and blood will be collected at baseline and at 4, 8, and 12 weeks. At the conclusion of the study patients will be told which diet they were on and will be provided with dietary consultation by a registered dietitian. Subjects who withdraw from the study before the 4 week assessment will be asked to provide a final stool sample at the time of withdrawal. If more than 2 subjects drop out prior to week 4, subject replacement will occur.

Official Title
-----------------
Randomized Trial of Diet for Crohn's Disease and Impact on Disease Activity and the Microbiome

Conditions
-----------------
Crohn Disease

Intervention / Treatment
-----------------
* Dietary Supplement: Diet 1
* Dietary Supplement: Diet 2


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Consentable adults of age 18 or older. Diagnosis of Crohn's disease made by a primary gastroenterologist based upon history, physical exam, laboratory/radiological studies, and endoscopy with biopsy. Fecal Calprotectin ≥ 300 Mild to moderate disease activity based upon a modified Harvey Bradshaw Index score of 5-16. On stable medication doses for ≥ 2 months. Exclusion Criteria: Inability/unwillingness to adhere to dietary recommendations. Allergy or intolerance to any major component of the diets. Major component defined as an ingredient which, when left out of intervention diets, may affect study outcomes. Allium intolerance Exclusively vegetarian diet Active intra-abdominal or perianal abscess/fistula Symptomatic bowel stricture Other serious medical conditions such as neurological, liver, kidney, autoimmune, or systemic disease Use of corticosteroids within 1 month prior to baseline visit Tobacco, alcohol, or illicit drug abuse Pregnant subjects Celiac disease Patients already on one of the diets being studied C. difficile or other enteric infection (O&P, stool enterics) Antibiotic use within 2 months prior to baseline visit

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diet 1<br>Administered for 8 weeks. | Dietary Supplement: Diet 1<br>* Diet controlled in amount and source of carbohydrates or fiber containing foods.<br>|
| Experimental: Diet 2<br>Administered for 8 weeks. | Dietary Supplement: Diet 2<br>* Diet controlled in amount and source of carbohydrates or fiber containing foods.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fecal Calprotectin Remission | To compare the proportion of patients with calprotectin remission (fecal calprotectin level < 250 and a decrease by ≥ 100 points) at 8 weeks post-dietary intervention for subjects on each diet | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fecal Calprotectin Response | Calprotectin response (decrease by ≥ 100 points) or calprotectin improvement (decrease by > 50%) at weeks 4 and 8 for subjects on each diet. Comparison of the mean calprotectin between the 2 treatment groups. | 8 weeks | 
| Clinical Response | Proportion of patients on each diet with clinical response (HBI score decrease by ≥ 3) or remission (HBI score < 5) at weeks 4 and 8 | 8 weeks | 
| Metagenomics | To compare changes in the metagenomics of the fecal microbiome at 8 weeks relative to baseline for each diet | 8 weeks | 
| Microbiota correlation with clinical disease activity and inflammatory biomarkers | To determine if changes in the microbiota are associated with changes in clinical disease activity (HBI score), or inflammatory biomarkers (fecal calprotectin, C-reactive protein, etc.). | 8 weeks | 
| Future Use | To collect stool and blood for potential future analysis looking at proteomics and metabolomics. | 8 weeks |