Clinical trial NCT02231814: The Crohn's Disease Exclusion Diet With Partial Enteral Nutrition or Alone in Adult Patients With Crohn's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Crohn's Disease
Keywords: Crohn's disease
Mild to moderate Crohn's Disease
Diet
Enteral Nutrition
Lead sponsor: Wolfson Medical Center
Sponsor class: OTHER_GOV
First posted: 2014-09-04
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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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Primary outcomes:
measure: Clinical remission defined as Harvey Bradshaw Index (HBI)<5
timeFrame: Week 6
Secondary outcomes:
measure: Steroid free remission between groups
timeFrame: Week 6, 12 and 24.
measure: Mucosal healing
timeFrame: Week 24-26
measure: Changes in mean C-Reactive Protein (CRP)
timeFrame: Weeks 6, 12 and 24.
measure: Change in mean fecal calprotectin
timeFrame: Week 6, 12 and 24
Other outcomes:
Locations:
city: Afula
country: Israel
facility: Haemek
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
Study officials:
affiliation: Wolfson Medical Center
name: Arie Levine, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tel Aviv Medical Center
name: Iris Dotan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rambam Medical Center,Haifa
name: Irit Hermesh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.