Trial of Specific Carbohydrate and Mediterranean Diets to Induce Remission of Crohn's Disease (DINE-CD)

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

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.

Study Overview

• Status: Completed
• Conditions: Crohn Disease
• Intervention / Treatment: Other: Diet

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 197
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • San Francisco, California, United States, 94115
      • UCSF Colitis and Crohn's Disease Center
  • Colorado
    • Denver, Colorado, United States, 80204
      • University of Colorado Denver
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Atlanta, Georgia, United States, 30342
      • Atlanta Gastroenterology
  • Illinois
    • Chicago, Illinois, United States, 60614
      • University of Chicago
    • Evanston, Illinois, United States, 60208
      • Northwestern University
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health University Hospital
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • The University of Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Baltimore
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Institute of Michigan
    • Troy, Michigan, United States, 48092
      • Troy Gastroenterology
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • The University of Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Minnesota Gastroenterology, P.A
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
    • New York, New York, United States, 10021
      • Weill Cornell - NewYork Presbyterian
    • New York, New York, United States, 10075
      • Lenox Hill Hospital
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • The University of North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Atrium Health (formerly Carolinas HealthCare System)
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University - Wexner Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Lifespan Health System
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53706
      • University of Wisconsin-Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Age ≥18
2. Documented diagnosis of Crohn's disease
3. sCDAI score >175
4. Documentation of receipt of a baseline stool sample by the data coordinating center and hsCRP.
5. Access to a computer with internet and the ability to complete daily online surveys
6. Capable of providing consent to participate
7. Able to receive weekly food shipments delivered every Friday for 6 weeks

Exclusion Criteria

1. Pregnancy
2. sCDAI >400
3. Hospitalized patients
4. Anticipated need for surgery within 6 weeks of randomization
5. Use of the Specific Carbohydrate Diet within 4 weeks of screening
6. Start or change*** dose of thiopurines (azathioprine and 6-MP), methotrexate, natalizumab, or vedolizumab within 12 weeks prior to screening
7. 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.
8. Start or change in dose of any 5-aminosalicylic acid (5-ASA) medications within 2 weeks of screening.
9. Start or change dose of corticosteroids within 1 week of screening or a dose >20mg/day prednisone or equivalent*
10. Use of antibiotics (other than topical formulations) for any reason within 2 weeks prior to screening
11. Known symptomatic intestinal stricture.
12. Presence of an ostomy
13. Baseline stool frequency >4 bowel movements/day when well
14. BMI <16
15. BMI ≥40
16. Celiac disease
17. Documented C difficile colitis within four weeks of screening
18. Diabetes Mellitus requiring medication
19. Albumin<2.0mg/dl, within 4 weeks of screening (if tested as part of routine clinical care)
20. Known allergy to tree nuts or peanuts
21. Other conditions that would be a contraindication to any of the study diets or preclude the participant from completing the study.

22. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Specific Carbohydrate Diet; 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; 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
Active Comparator: Mediterranean Style Diet; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Patient-Centered Outcomes Research Institute; University of North Carolina, Chapel Hill; Crohn's and Colitis Foundation

Publications and helpful links

General Publications

• Lewis JD, Sandler RS, Brotherton C, Brensinger C, Li H, Kappelman MD, Daniel SG, Bittinger K, Albenberg L, Valentine JF, Hanson JS, Suskind DL, Meyer A, Compher CW, Bewtra M, Saxena A, Dobes A, Cohen BL, Flynn AD, Fischer M, Saha S, Swaminath A, Yacyshyn B, Scherl E, Horst S, Curtis JR, Braly K, Nessel L, McCauley M, McKeever L, Herfarth H; DINE-CD Study Group. A Randomized Trial Comparing the Specific Carbohydrate Diet to a Mediterranean Diet in Adults With Crohn's Disease. Gastroenterology. 2021 Sep;161(3):837-852.e9. doi: 10.1053/j.gastro.2021.05.047. Epub 2021 May 27. Erratum In: Gastroenterology. 2022 Nov;163(5):1473.

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2017
• Primary Completion (Actual): March 1, 2020
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: February 16, 2017
• First Submitted That Met QC Criteria: February 16, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): July 21, 2021
• Last Update Submitted That Met QC Criteria: June 30, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: randomized controlled trial; diet; specific carbohydrate diet; Mediterranean style diet
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: 825907

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No