The Effects of Bifidobacterium Breve Bif195 for Small Intestinal Crohn's Disease

Study Overview
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Brief Summary
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The purpose of this study is to investigate if the probiotic Bifidobacterium breve Bif195 (Bif195) will result in improvement in clinical outcome in patients with small intestinal Crohn's disease.

Detailed Description
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Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) with an incidence rate at 11/100 000 per year in Denmark. The disease can potentially affect the entire gastrointestinal tract, though the most common affected area is terminal ileum and the adjacent part of colon. CD is a result of both genetic and environmental factors together with the intestinal microbiota, however the precise etiology is unclear. A change of the intestinal microbiota with a reduced occurrence of e.g. Bacteroides species, Firmicutes and the anti-inflammatory bacteria Faecalibacterium prausnitzii is found in CD patients compared to healthy controls. Also a reduction of the mucosa-associated Bifidobacteria has been associated with the risk of mucosal inflammation. The hypothesis that an imbalance between potentially beneficial and pathogenic bacteria contribute to the pathogenesis of IBD, including CD, has led to the suggestion that manipulation of the microbiota may be an attractive target for therapeutic interventions in IBD. A new probiotic bacterium, Bifidobacterium breve Bif195 (Bif195) has been identified and has shown great effects on preventing enteropathy and ulcers on the gut mucosa in healthy volunteers given acetylsalicylic acid (13), and thereby Bif195 has also shown a potential in reducing gut permeability defects. This bacterium has not yet been investigated in CD patients.

Official Title
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The Effects of Bifidobacterium Breve Bif195 for Small Intestinal Crohn's Disease: a Double-blind, Randomized, Placebo-controlled Study

Conditions
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Crohn Disease

Intervention / Treatment
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* Dietary Supplement: Bif195 capsules
* Dietary Supplement: Placebo capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with small intestinal CD Fecal calprotectin ≥ 250 ug/g IUS evidence of small bowel inflammation with wall thickness ≥ 4 mm At least 3 months af stable medical treatment Able to read and speak Danish Exclusion Criteria: Positive rectal swab for pathogenic microorganisms Use of antibiotics, probiotics and systemic glucocorticosteroids within 4 weeks prior to inclusion Participation in other clinical trials within 30 days prior to inclusion Pregnancy, planned pregnancy or breast feeding Psychiatric disease Abuse of alcohol or drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bif195 capsules<br>The capsule will contain approximately 15*10^9 CFU of Bif195 per day. Excipients: Microcrystalline Cellulose 6 mg per capsule, Magnesium Stearate 1.5 mg per capsule, Maltodextrin 277.8 mg per capsule, and Sodium Ascorbate 14.7 mg per capsule. | Dietary Supplement: Bif195 capsules<br>* 1 capsule daily for 8 weeks<br>|
| Placebo Comparator: Placebo capsules<br>The capsule contain only excipients: Microcrystalline Cellulose 6 mg per capsule, Magnesium Stearate 1.5 mg per capsule, Maltodextrin 277.8 mg per capsule, and Sodium Ascorbate 14.7 mg per capsule. | Dietary Supplement: Placebo capsules<br>* 1 capsule daily for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bowel Wall Thickness (BWT) from baseline measured by intestinal ultrasound (IUS) at 8 weeks | IUS will be performed in the non-fasting patient lying in supine position with a high-end ultrasound machine (Siemens Sequoia) with 10L4 transducer. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fecal calprotectin level from baseline at 8 weeks | measured from a fecal sample | 8 weeks | 
| Change in severity of symptoms from baseline measured by Harvey-Bradshaw index (HBI) at 8 weeks | HBI is a disease activity index for Crohns disease and consists of clinical parameters | 8 weeks | 
| Change in quality of life from baseline measured by Inflammatory Bowel Disease Questionnaire (IBDQ) Questionnaire Scores at 8 weeks | The IBDQ is a widely used instrument to assess QoL among IBD patients and consists of 32 questionaire | 8 weeks | 
| The change from baseline on Color Doppler Imaging Score (0-3) including inflammatory fat and ulceration (yes/no) at 8 weeks | measured by intestinal ultrasound (IUS) | 8 weeks | 
| Adverse and severe adverse events | Registered, if any events. Reported according to IHC-GCP | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Probiotics