Assessing the Tolerability of Oligosaccharide Supplementation in Patients With Crohn's Disease

Study Overview
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Brief Summary
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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
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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.

Official Title
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Assessing the Tolerability of Oligosaccharide Supplementation in Patients With Crohn's Disease: A Randomized, Controlled Trial

Conditions
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Crohn's Disease

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: Moderate Oligosaccharide Group
* Dietary Supplement: High Oligosaccharide Group


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>1 placebo muesli bars and 1 serving placebo muesli per day (0.55 g total fructans/GOS) | Dietary Supplement: Placebo<br>* 1 placebo muesli bar and 1 serving placebo muesli per day (0.55 g total fructans/GOS)<br>|
| Experimental: Moderate Oligosaccharide Group<br>1 placebo muesli bar and 1 serving intervention muesli per day (3.25 g total fructans/GOS) | Dietary Supplement: Moderate Oligosaccharide Group<br>* 1 placebo muesli bar and 1 serving intervention muesli per day (3.25 g total fructans/GOS)<br>|
| Experimental: High Oligosaccharide Group<br>1 intervention muesli bar and 1 serving intervention muesli per day (5.43 total fructans/GOS) | Dietary Supplement: High Oligosaccharide Group<br>* 1 placebo muesli bar and 1 serving placebo muesli per day (5.43 g total fructans/GOS)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in overall GI symptoms | The primary outcome will be the difference in overall gastrointestinal symptoms quantified by the VAS, at study completion compared to baseline, averaged over the 5-days in which the diet diaries are being completed among the 3 study groups. | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability assessment including overall gastrointestinal symptoms and specific symptoms | Secondary outcomes concerning tolerability will include differences in the individual gastrointestinal symptoms (abdominal bloating, abdominal pain, gut rumbling, flatulence) quantified by the VAS at study completion compared to baseline, averaged over the 5-days in which the diet diaries are being completed among the 3 study groups. | 4 weeks | 
| Fatigue assessment | Secondary endpoints concerning differences in the scores of the overall FIS (fatigue impact scale) and sub-categories (physical, cognitive, psychosocial) at study completion compared to baseline in all 3 study groups | 4 weeks | 
| Quality of Life Assessment | Secondary endpoints concerning differences in physical components summary (PCS) and the mental component summary (MSC) scores at study completion compared to baseline in all 3 study groups respectively | 4 weeks | 
| Mood Assessment | Secondary endpoints concerning mood that will include differences in state anxiety, state curiosity, state anger, and state depression scores of the STPI at study completion compared to baseline in all 3 study groups respectively | 4 weeks | 
| Disease Activity Asessment | The proportion of participants who relapse, as well as the time to relapse at study completion between groups. | 4 weeks | 
| Adherence Assessment | Adherence will be estimated and compared between groups at study completion | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's Disease