Clinical trial NCT02193750: Assessing the Tolerability of Oligosaccharide Supplementation in Patients With Crohn's Disease
Official title: Assessing the Tolerability of Oligosaccharide Supplementation in Patients With Crohn's Disease: A Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Crohn's Disease
Keywords: Crohn's Disease
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: The Alfred
name: Melbourne Health
First posted: 2014-07-18
Enrollment: 24
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: OTHER

Brief summary: The investigators hypothesize that a novel method for oligosaccharide supplementation, in the form of nutritional bars and/or muesli high in fructans and galacto-oligosaccharides (GOS), will be a safe and tolerable therapeutic intervention in patients with Crohn's disease (CD) in remission.

Detailed description: Subjects age \>/= 19 years with the diagnosis of CD for \>/= 6 months, currently in remission based on the Harvey-Bradshaw Index score (\</=4 points) and C-reactive protein (\<5 mg/L) will be recruited from two academic hospitals and affiliated gastroenterology outpatient clinics (St. Paul's Hospital, Vancouver, British Columbia, Canada; Alfred Hospital, Melbourne, Victoria, Australia).

The study is a randomized, double-blind, placebo-controlled trial that consist of a 2-week run-in period followed by a 4-week study period. Prior to study entry, a screening visit will be required for all potential participants. If a participant meets the inclusion criteria, they will be randomized to either a placebo (0.55 g total fructans/GOS), a moderate oligosaccharide group (3.25 g total fructans/GOS) or a high oligosaccharide group (5.43 g total fructans/GOS) through a computed-generated scheme within each respective center. During the run-in period, enrolled subjects will undergo the following: 1) Laboratory analyses (CBC, routine biochemistry, CRP and fecal calprotectin); 2) Stool collection for fecal calprotectin analysis; 3) tolerability assessment including overall gastrointestinal symptoms and specific symptoms (abdominal bloating, abdominal pain, gut rumbling, flatulence) utilizing a 100mm visual analogue scale (VAS, 0 = no symptoms; 100 = worst symptoms ever experienced); 4) fatigue assessment utilizing a multi-dimensional fatigue impact scale (FIS); 5) health-related quality of life (HRQOL) assessment utilizing the Short Form 36-Item Health Survey (SF-36) and 6) Mood assessment utilizing the Spielberger State-Trait Personality Inventory (STPI). Participants will also meet with a registered dietitian to quantify baseline oligosaccharide consumption by completing a prospective 5-day diet diary alongside a validated food frequency questionnaire (FFQ), the Monash University Comprehensive Nutritional Assessment Questionnaire (CNAQ) that assesses oligosaccharide intake in addition to the usual nutrients \[49\]. Once the initial dietary assessment is complete, participants will begin up-titration of their oligosaccharide supplementation in a step-wise fashion until they reach their required daily amounts defined by their treatment group allocation. Once this is achieved, they will enter the 4 weeks of treatment or at time of relapse. Participants will undergo re-assessment during the study period at 2 weeks (Visit #3), and at study completion (Visit #4).

If a participant undergoes a CD flare during the run-in period, they will be withdrawn from the study. The end point of the study will be at 4 weeks of treatment or at time of relapse.

Eligibility criteria: Inclusion Criteria:

* age \>/= 19 years
* diagnosed with CD for \>/= 6 months, currently in remission based on the Harvey-Bradshaw Index score (\</= 4 points) and C-reactive protein (\<5mg/L)

Exclusion Criteria:

* unable to provide informed consent;
* have significant hepatic, renal, endocrine, respiratory, neurological, or cardiovascular disease;
* confirmed diagnosis of celiac disease, or have suspected celiac disease and are following a gluten-free diet to manage symptoms with an elevated screening anti-tissue transglutaminase antibody test;
* significant complications of CD which includes a history of extensive colonic resection, including subtotal or total colectomy, history of \>/= 3 small bowel resections or received a diagnosis of short bowel syndrome, current ileostomy, colostomy or ileal-anal pouch, or a fixed symptomatic intestinal stenosis;
* antibiotic use in the 4 weeks prior to study start;
* use of any rectal preparations in the 2 weeks prior to study start;
* use of any non-steroidal anti-inflammatory drugs in the 2 weeks prior to study start;
* use of commercial probiotic supplements in the 4 weeks prior to study start
* change in CD therapy in the 4 weeks prior to study start (excluding steroid taper, however steroid dosing must be stable for 2 weeks prior to study start);
* recently been adhering to a novel dietary intervention for alternative health issues within the last 4 weeks prior to study start.

Primary outcomes:
measure: Difference in overall GI symptoms
timeFrame: 5 days
Secondary outcomes:
measure: Tolerability assessment including overall gastrointestinal symptoms and specific symptoms
timeFrame: 4 weeks
measure: Fatigue assessment
timeFrame: 4 weeks
measure: Quality of Life Assessment
timeFrame: 4 weeks
measure: Mood Assessment
timeFrame: 4 weeks
measure: Disease Activity Asessment
timeFrame: 4 weeks
measure: Adherence Assessment
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Department of Gastroenterology Alfred Hospital
city: Vancouver
country: Canada
facility: GI Clinic, St. Paul's Hospital
state: British Columbia
Study officials:
affiliation: Division of Gastroenterology, Department of Medicine St. Paul's Hospital, Vancouver, BC Cananda
name: Brian Bressler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Gastroenterology Alfred Hospital, Melbourne, Australia
name: Peter Gibson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Talley NJ, Abreu MT, Achkar JP, Bernstein CN, Dubinsky MC, Hanauer SB, Kane SV, Sandborn WJ, Ullman TA, Moayyedi P; American College of Gastroenterology IBD Task Force. An evidence-based systematic review on medical therapies for inflammatory bowel disease. Am J Gastroenterol. 2011 Apr;106 Suppl 1:S2-25; quiz S26. doi: 10.1038/ajg.2011.58. No abstract available.
citation: Kappelman MD, Rifas-Shiman SL, Kleinman K, Ollendorf D, Bousvaros A, Grand RJ, Finkelstein JA. The prevalence and geographic distribution of Crohn's disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol. 2007 Dec;5(12):1424-9. doi: 10.1016/j.cgh.2007.07.012. Epub 2007 Sep 29.
citation: Herrinton LJ, Liu L, Lewis JD, Griffin PM, Allison J. Incidence and prevalence of inflammatory bowel disease in a Northern California managed care organization, 1996-2002. Am J Gastroenterol. 2008 Aug;103(8):1998-2006. doi: 10.1111/j.1572-0241.2008.01960.x.
citation: Lichtenstein GR, Hanauer SB, Sandborn WJ; Practice Parameters Committee of American College of Gastroenterology. Management of Crohn's disease in adults. Am J Gastroenterol. 2009 Feb;104(2):465-83; quiz 464, 484. doi: 10.1038/ajg.2008.168. Epub 2009 Jan 6.
citation: Pai CG, Khandige GK. Is Crohn's disease rare in India? Indian J Gastroenterol. 2000 Jan-Mar;19(1):17-20.
citation: El Mouzan MI, Abdullah AM, Al Habbal MT. Epidemiology of juvenile-onset inflammatory bowel disease in central Saudi Arabia. J Trop Pediatr. 2006 Feb;52(1):69-71. doi: 10.1093/tropej/fmi039. Epub 2005 Jun 9.
citation: Ouyang Q, Tandon R, Goh KL, Ooi CJ, Ogata H, Fiocchi C. The emergence of inflammatory bowel disease in the Asian Pacific region. Curr Opin Gastroenterol. 2005 Jul;21(4):408-13.
citation: Aghazadeh R, Zali MR, Bahari A, Amin K, Ghahghaie F, Firouzi F. Inflammatory bowel disease in Iran: a review of 457 cases. J Gastroenterol Hepatol. 2005 Nov;20(11):1691-5. doi: 10.1111/j.1440-1746.2005.03905.x.
citation: Wright JP, Froggatt J, O'Keefe EA, Ackerman S, Watermeyer S, Louw J, Adams G, Girdwood AH, Burns DG, Marks IN. The epidemiology of inflammatory bowel disease in Cape Town 1980-1984. S Afr Med J. 1986 Jul 5;70(1):10-5.