Exclusive Enteral Nutrition in Patients With Ileocaecal Crohn's Disease

NCT04921033 | Unknown Phase 3 DMC

• 1 other identifier: EEN in ileocaecal Crohn's
• Study Type: interventional
• Target: 256
• Locations: 1 country
• Sites: 1

Brief Summary

Inflammatory bowel diseases are chronic and progressive entities, triggered by exposure to environmental factors in individuals with a genetic background. One of the most common environmental factors is the type of diet which is a key influencer on pathogenesis. Nutrients alter the intestinal microbiota, thus changing the intestinal permeability. The Western-type diet encompasses sugar, fat, and protein-rich products that have some deleterious effects on the intestinal microbiome compared to the plant-based Mediterranean-type diet. Based on this fact, diet-based therapeutic efforts have been used extensively in pediatric Crohn's disease patients and there is strong evidence that exclusive enteral nutrition (EEN) is as effective as corticosteroids to induce both clinical and endoscopic remission but this treatment strategy is underutilized in adults.

Conditions

Crohn Disease; Nutrient; Excess; Remission/Regression

Keywords

enteral nutrition; induction of remission; Crohn's disease

Outcome Measures

Primary Outcomes (2)

• Percentage of participants with mucosal healing

  Defined as Simple Endoscopic Score for Crohn's Disease (SES-CD) ≤2, at 12 weeks after randomization. The ileocolonoscopies will be evaluated by the site. SES-CD is an index for determining the severity of Crohn's disease. The SES-CD considers size of ulcerations, ulcerated surface, effected surface and the presence of narrowings, evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The score ranges from 0 to 60 where higher scores indicate more severe endoscopic activity.

  12 weeks

• Percentage of patients that tolerate the EEN by week 12

  Defined as withdrawal from the study from randomization through 12 weeks after randomization

  12 weeks

Secondary Outcomes (11)

• Endoscopic response

  12 weeks

• Mean change from baseline in SES-CD at 12 weeks after randomization

  12 weeks

• Mean change from baseline in CDAI over time (Time Frame: Baseline, 4, 8 and 12 weeks after randomization)

  12 weeks

• Time to clinical remission (Time frame: from randomization through 12 weeks after randomization)

  12 weeks

• Time to clinical response (Time frame: from randomization through 12 weeks after randomization)

  12 weeks

Study Arms (2)

Exclusive Enteral Nutrition

EXPERIMENTAL

35kcal/kg/day EEN (Nestle Modulen®) - Subjects will take medicine and EEN solution orally themselves.

Dietary Supplement: EEN (Nestle Modulen®)

Standard of care

ACTIVE COMPARATOR

* Budesonide 9mg/day for mild disease * Prednisolone 1mg/kg, maximum 40mg/day in decreasing doses (40mg for 4 weeks followed by a fixed taper for 6 weeks) for moderate-to-severe disease for 12 weeks. * Patients with moderate-to-severe disease in the steroid group will also receive 2mg/kg azathioprine. The dose of azathioprine will be adjusted according to abnormalities of white blood cell (WBC) count, platelet count, liver function tests (LFTs; i.e. alanine transaminase \[ALT\], aspartate transaminase \[AST\], alkaline phosphatase), lipase, blood urea nitrogen (BUN), and serum creatinine.

Drug: Standart of care

Interventions

EEN (Nestle Modulen®) DIETARY_SUPPLEMENT

35kcal/kg/day for every patient

Exclusive Enteral Nutrition

Standart of care DRUG

* Budesonide 9mg/day for mild disease * Prednisolone 1mg/kg, maximum 40mg/day in decreasing doses (40mg for 4 weeks followed by a fixed taper for 6 weeks) for moderate-to-severe disease for 12 weeks. * Patients with moderate to severe disease in the steroid group will also receive 2mg/kg azathioprine. The dose of azathioprine will be adjusted according to abnormalities of white blood cell (WBC) count, platelet count, liver function tests (LFTs; i.e. alanine transaminase \[ALT\], aspartate transaminase \[AST\], alkaline phosphatase), lipase, blood urea nitrogen (BUN), and serum creatinine.

Also known as: Budesonide (Budenofalk®), Prednisolone (Deltacortril®), Azathioprine (Imuran®)

Standard of care

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects, aged between 18-75 years with a diagnosis of ileocolonic Crohn's disease (CD) confirmed using endoscopy and/or imaging technology at most 3 months prior.
• Participant or his/her legal representative have voluntarily signed and dated an informed consent approved by and compliant with the requirements of this study protocol which has been approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) Adequate cardiac, renal, and hepatic function as determined by the Principal Investigator and demonstrated by Screening laboratory evaluations, questionnaires, and physical examination results that do not indicate an abnormal clinical condition that would place the participant at undue risk preclude participation in the study.
• Participant must be able to orally administer study medication/nutrient or have a designee or Healthcare Professional who can assist

You may not qualify if:

• Previous or current use of any medication for Crohn's disease such as biologics, immunomodulators (e.g., methotrexate, azathioprine, 6-mercaptopurine, JAK inhibitor, alpha-integrin), and corticosteroids
• Presence of complications (Fistula, abscess, fibrotic disease, imminent risk of surgery)
• Participants with a poorly controlled medical condition such as uncontrolled diabetes with a documented history of recurrent infections, unstable ischemic heart disease, moderate to severe congestive heart failure (New York Heart Association \[NYHA\] class III or IV), recent cerebrovascular accident, and any other condition which, in the opinion of the Investigator or the sponsor, would put the participant at risk by participation in the protocol
• Participants with positive C. difficile stool assay at screening.
• Rescue therapy with steroids, depending on the severity of the disease will be initiated for patients in the EEN group who do not respond clinically and will be excluded from the study. If the number of clinically unresponsive patients was greater than 25% of the total EEN population, the study will be stopped. Criteria for clinical response are described in the "Outcome Measures" section.

Sponsors & Collaborators

• Duzce University: lead

Study Sites (1)

Duzce University School of Medicine

Düzce, 81620, Turkey (Türkiye)

RECRUITING

MeSH Terms

Conditions

Crohn Disease

Interventions

Budesonide; Prednisolone; Methylprednisolone; Azathioprine

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols; Pregnadienes; Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Salih Tokmak

  Duzce University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Salih Tokmak

CONTACT

0905052532698; salihtokmak@duzce.edu.tr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Asistant Professor

Model Details: This is an open-label, randomized, multicenter, interventional, parallel-group study, designed to evaluate the efficacy and tolerability of EEN in inducing clinical remission at 12 weeks in subjects with ileocaecal CD. Patients will receive EEN for 8 weeks, initially building up to the full required volume of formula over the first 3 to 4 days, depending on tolerance and side effects After the completion of the period of EEN, foods will be reintroduced slowly and supplementary enteral nutrition will be continued for another 4 weeks. A total of 256 patients with ileocaecal CD will be randomized in a 1:1 ratio to receive steroids and EEN. Each of the treatment arms will comprise 128 subjects. In order to make the groups comparable, randomization will be stratified according to the severity of the disease according to Crohn's Disease Activity Index (CDAI): 1. CDAI between 150-220 --\> Mild 2. CDAI between 220-450 --\> Moderate 3. CDAI\>450 --\> Severe

Study Record Dates

• First Submitted: June 4, 2021
• First Posted: June 10, 2021
• Study Start: March 1, 2021
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: October 18, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After publication, for a year

Locations

TU (1)