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Exclusive Enteral Nutrition and Corticosteroids Therapy in Crohn's Disease (EENCD) (EENCD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03833596
Recruitment Status : Terminated (Low recruitment)
First Posted : February 7, 2019
Last Update Posted : September 2, 2020
Sponsor:
Collaborator:
Nestlé
Information provided by (Responsible Party):
Maria Ines Pinto Sanchez, McMaster University

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.

Condition or disease Intervention/treatment Phase
Crohn's Disease Drug: Prednisone Dietary Supplement: Exclusive Enteral Nutrition Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized control trial with three arms of treatment: EEN plus standard or short course of CS versus CS alone.
Masking: None (Open Label)
Masking Description: Treatment options are randomized and masked for participants and study staff until Visit 2, where participants and investigators are made aware of treatment arm.
Primary Purpose: Treatment
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
Actual Study Start Date : October 25, 2018
Actual Primary Completion Date : November 1, 2019
Actual Study Completion Date : November 1, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Prednisone

Arm Intervention/treatment
Active Comparator: Standard course CS with Regular Food
40 mg a day of oral Prednisone for 2 weeks with subsequent taper of daily dose by 5 mg per week.
Drug: Prednisone
All 3 arms will receive Prednisone - 2 will be standard course treatment, 1 will be short course and rapidly-tapered

Experimental: Standard course CS with EEN
40 mg a day of oral Prednisone for 2 weeks and taper of daily dose by 5 mg per week and Exclusive Enteral Nutrition for 6 weeks.
Drug: Prednisone
All 3 arms will receive Prednisone - 2 will be standard course treatment, 1 will be short course and rapidly-tapered

Dietary Supplement: Exclusive Enteral Nutrition
2 arms will receive EEN, in concurrence with either regular-course or short course and rapidly-tapered CS.
Other Name: Modulen (Nestlé)

Experimental: Short course CS with EEN
40 mg a day of oral Prednisone for 3 days and taper of daily dose by 5 mg every 3 days and Exclusive Enteral Nutrition for 6 weeks.
Drug: Prednisone
All 3 arms will receive Prednisone - 2 will be standard course treatment, 1 will be short course and rapidly-tapered

Dietary Supplement: Exclusive Enteral Nutrition
2 arms will receive EEN, in concurrence with either regular-course or short course and rapidly-tapered CS.
Other Name: Modulen (Nestlé)




Primary Outcome Measures :
  1. 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) [ Time Frame: 2 years ]
    Assess the efficacy of 6 weeks of EEN and CS in inducing remission (Crohn's Disease Activity Index (CDAI)<150) compared to treatment with CS alone in adult patients with active CD (CDAI>220 and either CRP>5 or fecal calprotectin >250mg/l)


Secondary Outcome Measures :
  1. Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing clinical disease improvement [ Time Frame: 2 years ]
    Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing clinical disease improvement (drop in Crohns Disease Activity Index - CDAI>70)

  2. Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in improving quality of life [ Time Frame: 2 years ]
    Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in improving quality of life (Short Inflammatory Bowel Disease Questionnaire (SIBDQ)) Total score ranges from 10 to 70 (higher values indicate better outcome). Subscales are divided into systemic (score range 2 to 14), social (score range 2 to 14), bowel (score range 3 to 21) and emotional (score range 3 to 21)

  3. Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing biochemical remission [ Time Frame: 2 years ]
    Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing biochemical remission (normalization of either serum CRP (CRP<5) and/or fecal calprotectin (less than 250mg/l)

  4. Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in normalizing colonic transit [ Time Frame: 2 years ]
    Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in normalizing colonic transit (SHAPE) among those with altered transit at baseline. Participants will take one capsule containing 24 markers and have an X-Ray done on day 5. If >20% markers (6 markers or more) are retained it is considered delayed transit.

  5. Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing anxiety and/or depression scores [ Time Frame: 2 years ]
    Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing anxiety and/or depression scores (decrease >2 points in Hospital Anxiety and Depression Scale. Total score ranges from 0 to 42, lower values indicating better outcome. Subscale HAD-A (anxiety) and HAD-D (depression) range from 0 to 21.

  6. Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in increasing body weight and improving nutritional status [ Time Frame: 2 years ]
    Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in increasing body weight and improving nutritional status (increased levels of micronutrients: vitamin A, vitamin B12, 25-hydroxy vitamin D, chromium, copper and zinc)

  7. Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing number of adverse events [ Time Frame: 2 years ]
    Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing number of adverse events

  8. Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing changes in microbiota composition [ Time Frame: 2 years ]
    Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing changes in microbiota composition (change in alpha diversity by 16S sequencing Illumina)

  9. Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing indirect markers of mucosal integrity [ Time Frame: 2 years ]
    Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing indirect markers of mucosal integrity (IFABP2)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03833596


Locations
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Canada, Ontario
McMaster University
Hamilton, ON, Ontario, Canada, L8S 4K1
Sponsors and Collaborators
McMaster University
Nestlé
Investigators
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Principal Investigator: Maria I Pinto-Sanchez, MD McMaster University
  Study Documents (Full-Text)

Documents provided by Maria Ines Pinto Sanchez, McMaster University:
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Responsible Party: Maria Ines Pinto Sanchez, Assistant Professor, Department of Medicine, McMaster University
ClinicalTrials.gov Identifier: NCT03833596    
Other Study ID Numbers: EEN in Crohn
First Posted: February 7, 2019    Key Record Dates
Last Update Posted: September 2, 2020
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Maria Ines Pinto Sanchez, McMaster University:
Corticosteroids
Exclusive Enteral Nutrition
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Prednisone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents