The Crohn's Disease Exclusion Diet With Partial Enteral Nutrition or Alone in Adult Patients With Crohn's Disease (CDED-AD)

Dietary Therapy Using the Crohn's Disease Exclusion Diet (CDED) With Partial Enteral Nutrition or Alone for Induction and Maintenance of Remission in in Adults With Mild to Moderate Crohn's Disease- A Pilot Study

This study will evaluate a novel diet for adult crohn's disease patients (The Crohn's Disease Exclusion Diet - CDED). Half of the patients in this study will receive the CDED alone while the other half will receive the CDED and a liquid diet formula, for 24 weeks.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Dietary supplement: Crohns Disease Exclusion Diet + PEN; Other: Crohns Disease Exclusion Diet

Detailed Description

Environmental factors, the microbiome (bacteria in our gut) and innate immunity all play a role in the pathogenesis of Crohn's disease .Exclusive enteral nutrition (EEN) was found to be effective for inducing remission in active pediatric Crohn's disease, while Partial Enteral Nutrition (PEN) with free diet was not; suggesting that the mechanism of EEN depends on exclusion of dietary components. Dietary factors may play a role in the pathogenesis of the disease, and maybe an important under-investigated therapeutic target.

"The Crohn's Disease Exclusion Diet" (CDED) is a palatable diet excluding components suspected to interfere with the bacteria in our gut or impair immune mechanisms. Our group previously evaluated 47 patients using the Crohn's disease Exclusion Diet + 50% Polymeric formula for 6 weeks, and demonstrated a 78% response rate and 70% disease remission rate using stringent criteria. This was accompanied by a highly significant reduction in markers for inflammation (C-reactive protein (CRP) and Erythrocyte Sedimentation Rate (ESR)), and normalization of CRP in 70% of those entering remission. Among these patients were 13 adults aged 19-32, the remission rate in these 13 patients was 69%, similar to the pediatric data. Importantly, 6/7 patients in this study who refused to drink formula and just used the diet achieved remission, suggesting that the exclusion and not partial enteral nutrition are responsible for the high remission rate. Our former study did not evaluate mucosal healing as an end point, since performing colonoscopies after 6- 12 weeks of therapy is neither ethical nor feasible in children.

At present, data about nutritional therapy and this new dietary approach have been generated primarily in children, and this new diet has not been evaluated for early mucosal healing. The objectives of this pilot study are to generate data in adults, evaluate the diet over a longer period of time (24 weeks) and evaluate mucosal healing. The study is a prospective open label randomized controlled pilot trial in adults, with mild to moderate Crohn's disease who will receive the Crohn's Disease Exclusion Diet (CDED) for 24 weeks.

If effective, this could enable use of a feasible, safe intervention for induction and maintenance of remission as a new therapy or as an adjunctive therapy with medical therapy.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Afula, Israel
    • Haemek
  • Holon, Israel
    • Wolfson Medical Center
  • Petach Tikva, Israel
    • Rabin Medical Center
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Informed consent
2. Established Crohn's disease
3. Aged 18-55
4. Duration of disease up to 5 years
5. Harvey Bradshaw Index 5 ≤( HBI) ≤15
6. Patients with uncomplicated disease involving the terminal ileum and or cecum
7. Patients who performed colonoscopy (or MR/CTEnterography with elevated calprotectin>200) demonstrating active disease in the previous 8 weeks

Exclusion Criteria

1. Patients with severe Disease (HBI > 15) or HBI<5
2. Pregnancy,
3. Patients with active extraintestinal disease, current B2 (Fixed non inflammatory stricture1 or small bowel obstruction) or B3 disease,
4. Patients who used immunomodulator <8 weeks, or had dose changed in past 8 weeks,
5. Patients with current or past use of biologics, or use of systemic steroids2,
6. Patients with deep ulcers involving the colon distal to the splenic flexure on most recent colonoscopy
7. Any proven current infection such as positive stool cultures or positive tests for parasites or C. difficile. Stool tests are mandatory only if diarrhea is present.
8. Active Perianal disease ( clarification-fistula with discharge or abscess)
9. Patients who have undergone an intestinal resection
10. Patients with systemic disease including: type 2 diabetes, kidney failure, liver failure, neurological disease, active heart disease and patients with active autoimmune condition requiring medication3
11. Patients unwilling to consume any animal source protein (eggs, chicken or fish).

Comments:

1. Patients with ileo-cecal valve narrowing maybe included
2. Patients active despite budesonide may enter the trial if they are on 3 mg, and stop budesonide within 14 days of commencement of the trial.

3. Patients with Celiac disease or Hashimoto Thyroiditis can be enrolled

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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: Group 1; Crohn's Disease Exclusion Diet+Partial Enteral Nutrition (PEN): Crohns Disease Exclusion Diet + PEN	Dietary supplement: Crohns Disease Exclusion Diet + PEN; Patients will use the CDED for a 24 week period, coupled with 1000 m"l of polymeric formula (1 Kcal/m"L) for the first 6 weeks. For weeks 7 to 24 patients will use the CDED coupled with 600 ml formula and a calcium supplement. The CDED is divided into 3 stages: 0-6 weeks induction phase, weeks 7-12 step down phase, weeks 13-24 maintenance phase.; Other Names: CDED + Liquid dietary formula
Experimental: Group 2; Crohn's Disease Exclusion Diet alone with a calcium supplement	Other: Crohns Disease Exclusion Diet; Crohn's Disease Exclusion Diet alone with a calcium supplement during the study (0-24). The CDED is divided into 3 stages: 0-6 weeks induction phase, weeks 7-12 step down phase, weeks 13-24 maintenance phase.; Other Names: CDED

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinical remission defined as Harvey Bradshaw Index (HBI)<5	Week 6

Secondary Outcome Measures

Outcome Measure	Time Frame
Steroid free remission between groups	Week 6, 12 and 24.
Mucosal healing	Week 24-26
Changes in mean C-Reactive Protein (CRP)	Weeks 6, 12 and 24.
Change in mean fecal calprotectin	Week 6, 12 and 24

Collaborators and Investigators

• Sponsor: Prof. Arie Levine
• Investigators: Principal Investigator: Arie Levine, MD, Wolfson Medical Center; Principal Investigator: Iris Dotan, MD, Tel Aviv Medical Center; Principal Investigator: Irit Hermesh, MD, Rambam Medical Center,Haifa

Publications and helpful links

General Publications

• Sigall-Boneh R, Pfeffer-Gik T, Segal I, Zangen T, Boaz M, Levine A. Partial enteral nutrition with a Crohn's disease exclusion diet is effective for induction of remission in children and young adults with Crohn's disease. Inflamm Bowel Dis. 2014 Aug;20(8):1353-60. doi: 10.1097/MIB.0000000000000110.
• Yanai H, Levine A, Hirsch A, Boneh RS, Kopylov U, Eran HB, Cohen NA, Ron Y, Goren I, Leibovitzh H, Wardi J, Zittan E, Ziv-Baran T, Abramas L, Fliss-Isakov N, Raykhel B, Gik TP, Dotan I, Maharshak N. The Crohn's disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn's disease (CDED-AD): an open-label, pilot, randomised trial. Lancet Gastroenterol Hepatol. 2022 Jan;7(1):49-59. doi: 10.1016/S2468-1253(21)00299-5. Epub 2021 Nov 2.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: August 27, 2014
• First Submitted That Met QC Criteria: September 1, 2014
• First Posted (Estimate): September 4, 2014

Study Record Updates

• Last Update Posted (Actual): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 29, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Diet; Crohn's disease; Enteral Nutrition; Mild to moderate Crohn's Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: 0105-14