Exclusive Enteral Nutrition in Patients With Ileocaecal Crohn's Disease

Crohn Disease Clinical Trial

Official title:

Exclusive Enteral Nutrition in Patients With Ileocaecal Crohn's Disease (XENIC): an Open-label, Multicenter, Prospective, Randomized Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04921033
• Other study ID #: EEN in ileocaecal Crohn's
• Status: Recruiting
• Phase: Phase 3
• Start date: March 1, 2021
• Est. completion date: January 1, 2026

Study information

• Verified date: October 2022
• Source: Duzce University
• Contact: Salih Tokmak
• Phone: 0905052532698
• Email: salihtokmak[@]duzce.edu.tr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 256
• Est. completion date: January 1, 2026
• Est. primary completion date: January 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Crohn Disease
• Nutrient; Excess

Intervention

Dietary Supplement:
• EEN (Nestle Modulen®)
35kcal/kg/day for every patient

Drug:
• Standart of care
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.

Locations

Country	Name	City	State
Turkey	Duzce University School of Medicine	Duzce

Sponsors (1)

Lead Sponsor	Collaborator
Duzce University

Country where clinical trial is conducted

Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Endoscopic response	Defined as decrease in SES-CD > 50% from baseline at 12 weeks after randomization	12 weeks
Secondary	Mean change from baseline in SES-CD at 12 weeks after randomization	Mean change from baseline in SES-CD	12 weeks
Secondary	Mean change from baseline in CDAI over time (Time Frame: Baseline, 4, 8 and 12 weeks after randomization)	The Crohn's Disease Activity Index (CDAI) is a research tool used to quantify the symptoms of patients with Crohn's disease. Participants were asked to record the frequency of stools, abdominal pain and general well-being on a daily basis. In addition to the diary data, the investigator assessed the following for the calculation of CDAI: presence of complications (arthritis/arthralgia, iritis/uveitis, erythema nodosum/pyoderma gangrenosum/aphthous stomatitis, anal fissure/fistula/abscess, other fistula, and fever), the use of antidiarrheal medicines, presence of an abdominal mass, hematocrit, and body weight. The CDAI is the sum of the products of each item multiplied by a weighting factor and generally ranges from 0 up to 600, where remission of Crohn's disease is defined as CDAI < 150, and severe disease is defined as CDAI > 450. A negative change from baseline indicates improvement.	12 weeks
Secondary	Time to clinical remission (Time frame: from randomization through 12 weeks after randomization)	Clinical remission was defined as: CDAI < 150; PRO-2 abdominal pain (AP) score=1 (7 day average) and liquid/very soft stool frequency (SF) score=3 (7 day average); Two-item Patient Reported Outcome (PRO-2) is a health outcome directly reported by the patient to quantify a treatment's efficacy that is derived from CDAI diary card. Participants were asked to record daily number of liquid or very soft stools and the severity of abdominal pain (defined as; 0=none, 1=mild, 2=moderate 3=severe). PRO-2 is the sum of the products of each item multiplied by a weighing factor. PRO-2 scores that correspond to CDAI thresholds are: Mild Moderate Severe CDAI 150 220 450 PRO-2 8 14 34	12 weeks
Secondary	Time to clinical response (Time frame: from randomization through 12 weeks after randomization)	Clinical response was defined as: CDAI reduction =100 from baseline; PRO-2 reduction =8 from baseline	12 weeks
Secondary	Mean change from baseline in C-reactive protein (CRP) over time (Time Frame: 4, 8 and 12 weeks after randomization)	Changes in CRP levels	12 weeks
Secondary	Mean change from baseline in fecal calprotectin (FC) over time (Time Frame: 4, 8 and 12 weeks after randomization)	Changes in fecal calprotectin levels	12 weeks
Secondary	Mean change from baseline in PRO-2 (Time Frame: Baseline and 12 weeks after randomization)	Two-item Patient Reported Outcome (PRO-2) is a health outcome directly reported by the patient to quantify a treatment's efficacy that is derived from CDAI diary card. Participants were asked to record daily number of liquid or very soft stools and the severtiy of abdominal pain (defined as; 0=none, 1=mild, 2=moderate 3=severe). PRO-2 is the sum of the products of each item multiplied by a weighing factor. PRO-2 scores that correspond to CDAI thresholds are: Mild Moderate Severe CDAI 150 220 450 PRO-2 8 14 34	12 weeks
Secondary	Change from baseline in SIBDQ total score (Time Frame: Baseline and 12 weeks after randomization)	Short Inflammatory Bowel Disease Questionnaire (SIBDQ) is a 10-item HrQOL questionnaire designed to quantify the changes in patients' daily activity, related to Crohn's disease symptoms. Participants were asked questions about physical, social, emotional, and systemic aspects and scored on a 7-point scale from 1 (severe problem) to 7 (no problems at all). The score ranges from 1 to 70 where higher scores indicate better HrQOL.	12 weeks
Secondary	Change in Robarts Histopathology Index (RHI) (Time Frame: Baseline and 12 weeks after randomization)	RHI is a research tool used to quantify the histologic changes and to assess the degree of inflammation in the mucosa.; RHI= 1xchronic inflammatory infiltrate level (4 levels); 2 x lamina propria neutrophils (4 levels); 3 x neutrophils in epithelium (4 levels); 5 x erosion or ulceration (4 levels); The total score ranges from 0 (no disease activity) to 33 (severe disease activity). RHI=3 corresponds to histologic remission.	12 weeks
Secondary	Number of Crohn's disease-related hospitalizations after randomization (Time Frame: From randomization through 12 weeks after randomization)	Hospitalization was defined as a visit to hospital/clinic resulting in admission and overnight stay in hospital/clinic. Hospitalization due to emergency was defined as a hospitalization admitted through the emergency department.	12 weeks