Clinical trial NCT04921033: Exclusive Enteral Nutrition in Patients With Ileocaecal Crohn's Disease
Official title: Exclusive Enteral Nutrition in Patients With Ileocaecal Crohn's Disease (XENIC): an Open-label, Multicenter, Prospective, Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Crohn Disease
Nutrient; Excess
Remission/Regression
Keywords: enteral nutrition
induction of remission
Crohn's disease
Lead sponsor: Duzce University
Sponsor class: OTHER
First posted: 2021-06-10
Enrollment: 256
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Percentage of participants with mucosal healing
timeFrame: 12 weeks
measure: Percentage of patients that tolerate the EEN by week 12
timeFrame: 12 weeks
Secondary outcomes:
measure: Endoscopic response
timeFrame: 12 weeks
measure: Mean change from baseline in SES-CD at 12 weeks after randomization
timeFrame: 12 weeks
measure: Mean change from baseline in CDAI over time (Time Frame: Baseline, 4, 8 and 12 weeks after randomization)
timeFrame: 12 weeks
measure: Time to clinical remission (Time frame: from randomization through 12 weeks after randomization)
timeFrame: 12 weeks
measure: Time to clinical response (Time frame: from randomization through 12 weeks after randomization)
timeFrame: 12 weeks
measure: Mean change from baseline in C-reactive protein (CRP) over time (Time Frame: 4, 8 and 12 weeks after randomization)
timeFrame: 12 weeks
measure: Mean change from baseline in fecal calprotectin (FC) over time (Time Frame: 4, 8 and 12 weeks after randomization)
timeFrame: 12 weeks
measure: Mean change from baseline in PRO-2 (Time Frame: Baseline and 12 weeks after randomization)
timeFrame: 12 weeks
measure: Change from baseline in SIBDQ total score (Time Frame: Baseline and 12 weeks after randomization)
timeFrame: 12 weeks
measure: Change in Robarts Histopathology Index (RHI) (Time Frame: Baseline and 12 weeks after randomization)
timeFrame: 12 weeks
measure: Number of Crohn's disease-related hospitalizations after randomization (Time Frame: From randomization through 12 weeks after randomization)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Duzce
country: Turkey
facility: Duzce University School of Medicine
Study officials:
affiliation: Duzce University
name: Salih Tokmak
role: PRINCIPAL_INVESTIGATOR
References: