Clinical trial NCT03833596: Exclusive Enteral Nutrition and Corticosteroids Therapy in Crohn's Disease (EENCD)
Official title: Synergistic Effect of Exclusive Enteral Nutrition Formula in Addition to Corticosteroids Therapy to Induce Clinical Remission in Patients With Crohn's Disease: a Pilot Study Involving a Multidimensional Assessment of Potential Mechanisms
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Crohn's Disease
Keywords: Corticosteroids
Exclusive Enteral Nutrition
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Société des Produits Nestlé (SPN)
First posted: 2019-02-07
Enrollment: 3
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: Randomized control trial with three arms of treatment: EEN plus standard or short course of CS versus CS alone.
Primary purpose: TREATMENT

Brief summary: This study evaluates the effect of Exclusive Enteral Nutrition (EEN) in addition to different regimes of corticosteroid (CS) therapy (Prednisone) compared to CS alone in adults participants with active Crohn's Disease, on symptoms and inflammation after 6 weeks of treatment. Participants will be randomized to three treatment arms: standard CS, standard CS with EEN, short course CS with EEN. Participants will be assessed through questionnaires for gut symptoms, quality of life, mood changes and dietary patterns and potential mechanisms will be investigated by collecting stool samples for characterization of gut bacterial profiles, collection of blood to determine inflammatory markers and evaluation of gut motility before and after treatment. The investigators hypothesize that six weeks of EEN with CS will be more effective than CS alone in inducing clinical remission in patients with active CD, as well as leading to beneficial changes in the composition and/or metabolic activity of the intestinal microbiota, gastrointestinal transit and inflammatory burden. Furthermore, six weeks of EEN in addition to a short course of CS will have similar efficacy than EEN with standard course of CS and reduced number of adverse events.

Detailed description: Crohn's disease (CD) is an inflammatory bowel disease (IBD) characterized by diarrhea, abdominal pain and bleeding. There are several treatment options but the most-widely used for acute therapy are corticosteroids (CS), however, CS are often associated with severe side effects. The administration of a formula for exclusive feeding (EEN) is well-established as an alternative to CS in children with Crohn's disease (CD). EEN has been proposed to reduce inflammation in the gut. However, this intervention is not routinely used in adults, in part because of uncertainty regarding the magnitude of the benefit of EEN reported in previous studies. Although few studies have examined the effects of EEN in adult patients with active CD, the potentially synergistic effects of adding EEN to the conventional CS was not explored. Furthermore, it is also possible that the addition of EEN allows to decrease the duration of CS therapy; however, this was not investigated before.

The investigators propose that an oral formula may help decrease gut inflammation and improve nutritional status through modulation of gut bacteria. The investigators will therefore evaluate the effect of exclusive formula feeding therapy in addition to different regimes of CS therapy compared to CS alone in adult patients with active CD, on symptoms and inflammation after 6 weeks of treatment. Participants will be randomized to three treatment arms: standard CS, standard CS with EEN, short course CS with EEN. The investigators will collect information through questionnaires that assess gut symptoms, quality of life, mood changes and dietary patterns. To investigate potential mechanisms, the investigators will collect stool samples to characterize gut bacterial profiles, blood to determine inflammatory markers and evaluate gut movements (motility) before, and after the treatment. The investigators hope that the results will lead to better understanding of the beneficial effect of exclusive formula feeding in addition to CS as a more efficacious alternative than CS alone, and to understand the mechanisms of this therapy.

Eligibility criteria: Inclusion Criteria:

* Confirmed CD for at least 6 months
* Clinically active disease (CDAI \>220 or Harvey-Bradshaw Index (HBI) \>6) or active by endoscopy.
* Biochemical evidence of disease activity (CRP \>5 and/or fecal calprotectin \>250)

Exclusion Criteria:

* Currently using EEN
* Condition that would preclude the use of EEN, such as Intestinal obstruction, perforation, toxic megacolon, massive gastrointestinal bleeding, abdominal abscess, or stricturing disease
* Previous intestinal resection with a remnant bowel of less than 180 cm
* Treatment with Prednisone in the last 30 days
* New start or change in dose of azathioprine, 6-mercaptopurine, cyclosporine, other immunosuppressant or biologics in the last 90 days. Doses of these medications must also remain unchanged for the duration of the study
* New start or change in dose of 5-aminosalicylic acid (ASA) in the last 30 days. 5ASA dose must remain unchanged for the duration of the study
* Use of Antibiotics or Probiotics in the last 30 days
* Pregnant or Lactating
* Any serious illness which could interfere with study procedures or results

Primary outcomes:
measure: Efficacy of 6 weeks of EEN and CS in inducing remission (Crohn's Disease Activity Index - CDAI<150) in adult patients with active CD (CDAI>220 and either CRP>5 or fecal calprotectin >250mg/l)
timeFrame: 2 years
Secondary outcomes:
measure: Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing clinical disease improvement
timeFrame: 2 years
measure: Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in improving quality of life
timeFrame: 2 years
measure: Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing biochemical remission
timeFrame: 2 years
measure: Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in normalizing colonic transit
timeFrame: 2 years
measure: Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing anxiety and/or depression scores
timeFrame: 2 years
measure: Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in increasing body weight and improving nutritional status
timeFrame: 2 years
measure: Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing number of adverse events
timeFrame: 2 years
measure: Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing changes in microbiota composition
timeFrame: 2 years
measure: Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing indirect markers of mucosal integrity
timeFrame: 2 years
Other outcomes:
Locations:
city: Hamilton, ON
country: Canada
facility: McMaster University
state: Ontario
Study officials:
affiliation: McMaster University
name: Maria I Pinto-Sanchez, MD
role: PRINCIPAL_INVESTIGATOR
References: