Trial of Specific Carbohydrate and Mediterranean Diets to Induce Remission of Crohn's Disease

Study Overview
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Brief Summary
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This protocol is designed to compare the effectiveness of two dietary interventions for patients with Crohn's disease (CD): the Specific Carbohydrate Diet (SCD) and a Mediterranean style diet (MSD) that has been demonstrated to have numerous other health benefits. The two diets will be compared in terms of their ability to resolve both the symptoms and bowel inflammation that characterize this debilitating disease.

Detailed Description
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This study tested whether the SCD is superior to a MSD for managing symptoms and reducing inflammatory markers in patients with CD. The study was designed to include 194 patients with CD who have 1) active symptoms defined by a short Crohn's Disease Activity Index (sCDAI) score >175. Although the initial plan was to also require that all patients have active inflammation documented by a fecal calprotectin (FCP) concentration >250mcg/g or high sensitivity C-reactive protein (CRP) >7 mg/L or ulceration of the small bowel and/or colon consistent with an SES-CD score >4 as documented in routine clinical practice within 4 weeks of screening, a decision was made early in the recruitment period to enroll all patients with CD with sCDAI>175 regardless of the results of the tests for inflammatory markers and to perform subgroup analyses of those with and without evidence of inflammation. Eligible participants were randomly assigned to follow one of the diets in a 1:1 ratio. Participants were provided with 3 meals and 2 snacks each day for a period of 6 weeks. The meals and snacks were prepared by the food vendor, Healthy Chef Creations, and were delivered directly to the participant's home once per week. Participants in both groups were also provided with instructions on how to follow the diets on their own. Participants reported their symptoms through an electronic diary and provided stool samples for FCP measurement and blood for CRP measurement at weeks 0, 6 and 12. The primary and secondary outcomes were assessed at week 6. Following week 6, participants were able to pay out of pocket to purchase food from Healthy Chef Creations and/or could attempt to follow their assigned diet completely on their own. At week 12, in addition to the primary and secondary outcomes assessed again

Official Title
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Open Label, Randomized, Multicenter, Comparative Effectiveness Trial of Specific Carbohydrate and Mediterranean Diets to Induce Remission in Patients With Crohn's Disease

Conditions
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Crohn Disease

Intervention / Treatment
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* Other: Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age ≥18 Documented diagnosis of Crohn's disease sCDAI score >175 Documentation of receipt of a baseline stool sample by the data coordinating center and hsCRP. Access to a computer with internet and the ability to complete daily online surveys Capable of providing consent to participate Able to receive weekly food shipments delivered every Friday for 6 weeks Exclusion Criteria Pregnancy sCDAI >400 Hospitalized patients Anticipated need for surgery within 6 weeks of randomization Use of the Specific Carbohydrate Diet within 4 weeks of screening Start or change*** dose of thiopurines (azathioprine and 6-MP), methotrexate, natalizumab, or vedolizumab within 12 weeks prior to screening Start or change*** dose of anti-tumor necrosis factor (TNF) agents (including infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), golimumab (Simponi) or ustekinumab within 8 weeks prior to screening. Start or change in dose of any 5-aminosalicylic acid (5-ASA) medications within 2 weeks of screening. Start or change dose of corticosteroids within 1 week of screening or a dose >20mg/day prednisone or equivalent* Use of antibiotics (other than topical formulations) for any reason within 2 weeks prior to screening Known symptomatic intestinal stricture. Presence of an ostomy Baseline stool frequency >4 bowel movements/day when well BMI <16 BMI ≥40 Celiac disease Documented C difficile colitis within four weeks of screening Diabetes Mellitus requiring medication Albumin<2.0mg/dl, within 4 weeks of screening (if tested as part of routine clinical care) Known allergy to tree nuts or peanuts Other conditions that would be a contraindication to any of the study diets or preclude the participant from completing the study. Currently participating in another clinical trial of a drug to treat Inflammatory Bowel Disease (IBD) or a dietary therapy for any indication. Patients may continue these medications at stable dose for the first six weeks and budesonide may be used at any dose. After the 6th week in the study, patients may taper their steroid dose. The study will provide a recommended taper schedule. Loading/induction doses of biologic type medication will be considered a stable doses. ***Exception for treatment failures: if a subject is determined to fail on any of the following standard lines of treatment at the treating investigator's discretion, subjects may screen for study intervention based upon the following wash out periods: 4 weeks for thiopurine and methotrexate and 8 weeks for natalizumab, vedolizumab, anti-TNF, or ustekinumab.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Specific Carbohydrate Diet<br>For the first six 6 weeks of the trial, participants received a weekly delivery of prepared meals compliant with the SCD (breakfast, lunch, dinner, and two 2 snacks per day). Meals were prepared by Healthy Chef Creations (Orlando, FL) based on menus developed by the food vendor in consultation with study dietitians. Participants assigned to the SCD received a three3-day starter diet as recommended in Breaking the Vicious Cycle. Meals were designed to be heated in an oven or microwave. No other preparation was required. | Other: Diet<br>* food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks<br>|
| Active Comparator: Mediterranean Style Diet<br>For the first six 6 weeks of the trial, participants received a weekly delivery of prepared meals compliant with the MD (breakfast, lunch, dinner, and two 2 snacks per day). Meals were prepared by Healthy Chef Creations (Orlando, FL) based on menus developed by the food vendor in consultation with study dietitians. Meals were designed to be heated in an oven or microwave. No other preparation was required. | Other: Diet<br>* food for the diet will be provided to the participants for 6 weeks and participants will follow the diet on their own for the remaining 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants That Achieved Symptomatic Remission at Week 6 | Assessed by Short Crohn's Disease Activity Index (sCDAI) - diarrhea, abdominal pain and general well being; sCDAI <150 in the absence of initiation or increase of any CD medications | 6 weeks | 
| Reduction in Bowel Inflammation Among Those Whose Screening Fecal Calprotectin (FC) Was Greater Than 250μg/g at Baseline and Who Had an FC Results at Both Baseline and Week 6 | reduction of calprotectin to less than 250 μg/g and by greater than 50% from screening among those with screening FC >250 μg/g | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants That Reached Clinical Remission at Week 6 | Assessed by the CDAI - CDAI <150 | 6 weeks | 
| Percentage of Participants With a Reduction in Systemic Inflammation at Week 6 | reduction in high-sensitivity CRP (hsCRP) to <5 mg/L and >50% reduction from screening among those with screening hsCRP >5mg/L | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diet, specific carbohydrate diet, Mediterranean style diet, randomized controlled trial