Ulcerative Colitis Relapse Prevention by Prebiotics

NCT02865707 | Completed DMC

• 1 other identifier: Pro00041938
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

Ulcerative colitis (UC) is a relapsing chronic intestinal inflammation with no existing cure, that affects over 300 per 100.000 Canadians, the highest prevalence in the world. The standard drug therapies are expensive and potentially toxic, and mostly directed against the chronic inflammatory process. UC is the result of a dysbiosis between disease-inducing and protective intestinal bacteria in a genetically susceptible host. Non-digestible dietary carbohydrates (NDC) stimulate the growth of protective endogenous intestinal bacteria which ferment them into short-chain fatty acids (SCFA), some of the latter with natural anti-inflammatory properties, and are called prebiotics. The investigator was the first to report that oral intake of NDC, the dietary β-fructans inulin plus fructo-oligosaccharides (FOS), reduced colitis in a genetically-induced rat colitis model. Both inulin and FOS reduced colitis, each NDC modifying specific luminal microbiota. A small trial with the same mixture of NDC in patients with active UC relapsing on oral 5-aminosalicylic acid (5-ASA) showed a dose-dependent clinical response, confirming the translational potential of this NDC mixture. The investigators propose a randomized placebo-controlled trial to assess if inulin plus FOS can also prevent such relapses in UC patients with inactive disease on stable maintenance drugs. Primary hypothesis is that inulin plus FOS is effective adjunct therapy to standard drugs for maintaining clinical remission. The second hypothesis is that the colonic microflora and its metabolic function, altered by inulin plus FOS, or not, mediate protection or relapse in UC. The longitudinal design of this maintenance prevention study and by serially collecting colon biopsies, stool, serum and urine within the same patient before a relapse (inflammation) occurs, would enable to identify unique changes in the intestinal microbiota, their metabolic functions and also assess effects on host-immune response that are associated with remission or before a relapse occurs during treatment with beta-fructans, or not.

Conditions

Ulcerative Colitis

Keywords

ulcerative colitis; prebiotics; b-fructans; inulin; oligofructose; intestinal microbiota

Outcome Measures

Primary Outcomes (1)

• Prevention of relapse

  The percentage of patients that experienced relapse during the treatment period in prebiotic group versus that in the placebo group. Percentage will be calculated using the number of patients that relapse divided to the total number of patients in the treatment group. Relapse is defined as an total Mayo score of 3 or more with an endoscopy grade equal to or more than 2, and rectal bleeding for at least 3 days.

  6 months

Secondary Outcomes (6)

• Time to relapse

  6 months

• Patient compliance

  3 and 6 month

• Patient tolerability

  3 and 6 month

• Changes in endoscopic disease activity inflammation

  0 and 6 month

• Changes in fecal calprotectin

  0, 1, 3 and 6 month

Study Arms (2)

Prebiotic

EXPERIMENTAL

Prebiotic group will take 15 grams of prebiotic product Synergy-1 per day for 6 months. Synergy-1 is chicory-derived β-fructans inulin plus FOS (1:1). During the first two weeks the patient is advised to take 7.5 g of the product at breakfast only. Starting in week 3 until the end of the treatment the participant will take 7.5 g at breakfast and 7.5 g at dinner for a total of 6 months, or until you experience a flare.

Dietary Supplement: Synergy-1

Placebo

PLACEBO COMPARATOR

Placebo group will take 15 grams of maltodextrin per day for 6 months. Maltodextrin is a sugar adsorbed in the small bowel with no effect on the colonic intestinal microbiota. During the first two weeks the patient is advised to take 7.5 g of the product at breakfast only. Starting in week 3 until the end of the treatment the participant will take 7.5 g at breakfast and 7.5 g at dinner for a total of 6 months, or until you experience a flare.

Dietary Supplement: Maltodextrin

Interventions

Synergy-1 DIETARY_SUPPLEMENT

Synergy-1 is chicory-derived β-fructans inulin plus FOS (1:1).

Prebiotic

Maltodextrin DIETARY_SUPPLEMENT

Maltodextrin is carbohydrate adsorbed in the small bowel.

Placebo

Eligibility Criteria

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

You may qualify if:

• Patients with Ulcerative colitis (UC) with confirmed diagnosis by histology and endoscopy.
• Currently in clinical remission defined as total Mayo score of ≤ 2 and endoscopic score of 0 or 1) who have experienced at least one flare in the past 18 months.
• On stable doses of oral 5-ASA for 2 weeks and/or a stable doses of azathioprine and/or anti-tumor necrosis factor (anti-TNF) biologics for 2 months
• Colonic involvement of \>15 cm from the anal verge.
• Ability to give valid informed consent
• For females of child bearing potential, a negative pregnancy test and an agreement to use appropriate birth control over the study period.

You may not qualify if:

• Crohn's disease, indetermined colitis or infectious colitis.
• Active UC, (total Mayo score of ≥ 3)
• Taking prednisone (or steroid equivalent) within 1 month of enrollment
• Used topical 5-ASA or steroids within 2 weeks of enrollment
• Using immunosuppressive treatments of 6-mercaptopurine or methotrexate
• Used antibiotics within 2 months
• Used anti-diarreal agents with the previous 3 days
• Pregnancy or lactation
• Significant chronic disorders such as severe cardiac disease, significant renal failure, severe pulmonary disease (need for oxygen)
• Active gastrointestinal infection
• Severe psychiatric disorder
• Not able to consent to the study.

Sponsors & Collaborators

• University of Alberta: lead
• University of British Columbia: collaborator

Study Sites (1)

University of Alberta

Edmonton, Alberta, T6G 2E1, Canada

Location

Related Publications (1)

• Armstrong HK, Bording-Jorgensen M, Santer DM, Zhang Z, Valcheva R, Rieger AM, Sung-Ho Kim J, Dijk SI, Mahmood R, Ogungbola O, Jovel J, Moreau F, Gorman H, Dickner R, Jerasi J, Mander IK, Lafleur D, Cheng C, Petrova A, Jeanson TL, Mason A, Sergi CM, Levine A, Chadee K, Armstrong D, Rauscher S, Bernstein CN, Carroll MW, Huynh HQ, Walter J, Madsen KL, Dieleman LA, Wine E. Unfermented beta-fructan Fibers Fuel Inflammation in Select Inflammatory Bowel Disease Patients. Gastroenterology. 2023 Feb;164(2):228-240. doi: 10.1053/j.gastro.2022.09.034. Epub 2022 Sep 29.

  PMID: 36183751 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

maltodextrin

Condition Hierarchy (Ancestors)

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

Study Officials

• Levinus A Dieleman, MD, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2016
• First Posted: August 12, 2016
• Study Start: August 1, 2016
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: April 14, 2022

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)