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

• ClinicalTrials.gov Identifier: NCT03058679
• Recruitment Status: Completed
• First Posted: February 23, 2017
• Results First Posted: July 21, 2021
• Last Update Posted: July 21, 2021
• Sponsor: University of Pennsylvania
• Collaborators: Patient-Centered Outcomes Research Institute; Crohn's and Colitis Foundation; University of North Carolina, Chapel Hill
• Information provided by (Responsible Party): University of Pennsylvania

Tracking Information

• First Submitted Date: February 16, 2017
• First Posted Date: February 23, 2017
• Results First Submitted Date: March 26, 2021
• Results First Posted Date: July 21, 2021
• Last Update Posted Date: July 21, 2021
• Actual Study Start Date: September 29, 2017
• Actual Primary Completion Date: March 1, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 30, 2021)

• Percentage of Participants That Achieved Symptomatic Remission at Week 6 [ Time Frame: 6 weeks ]
  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
• 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 [ Time Frame: 6 weeks ]
  reduction of calprotectin to less than 250 μg/g and by greater than 50% from screening among those with screening FC >250 μg/g

Original Primary Outcome Measures (submitted: February 16, 2017)

• Symptomatic remission [ Time Frame: 6 weeks ]
  Assessed by Short Crohn's Disease Activity Index - diarrhea, abdominal pain and general well being
• Reduction in bowel inflammation [ Time Frame: 6 weeks ]
  Calprotectin <250 mcg/gm and >50% reduction from baseline

Current Secondary Outcome Measures (submitted: June 30, 2021)

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

Original Secondary Outcome Measures (submitted: February 16, 2017)

• Clinical remission [ Time Frame: 6 weeks ]
  Assessed by the Harvey Bradshaw Index
• Reduction in systemic inflammation [ Time Frame: 6 weeks ]
  hsCRP < 5mg/L >50% reduction from baseline

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Crohn Disease

Intervention

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

Study Arms

• 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.
  Intervention: Other: Diet
• 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.
  Intervention: Other: Diet

• Publications *: Lewis JD, Sandler R, Brotherton C, Brensinger C, Li H, Kappelman MD, Daniel SG, Bittinger K, Albenberg L, Valentine JF, Hanson J, Suskind D, Meyer A, Compher CW, Bewtra M, Saxena A, Dobes A, Cohen B, 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 May 27. pii: S0016-5085(21)03069-9. doi: 10.1053/j.gastro.2021.05.047. [Epub ahead of print]

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 30, 2021): 197
• Original Estimated Enrollment (submitted: February 16, 2017): 194
• Actual Study Completion Date: March 1, 2020
• Actual Primary Completion Date: March 1, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03058679
• Other Study ID Numbers: 825907
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: University of Pennsylvania
• Study Sponsor: University of Pennsylvania

Collaborators

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

Investigators

• Principal Investigator: James D Lewis, MD, MSCE; University of Pennsylvania

• PRS Account: University of Pennsylvania
• Verification Date: June 2021