Colesevelam for the Treatment of Bile Acid Malabsorption in Patients With Crohn's Disease

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy of cholestagel to reduce the frequency of soft and liquid stools per day in patients with CD in clinical remission with symptoms of BAM and to assess the improvement in stool consistency and quality of life in these patients and to assess the safety of cholestagel.

Official Title
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Colesevelam for the Treatment of Bile Acid Malabsorption in Patients With Crohn's Disease

Conditions
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Crohns Disease, Bile Acid Malabsorption

Intervention / Treatment
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* Drug: Colesevelam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Signed informed consent after adequate explanation of the patient information. Male and female patients with CD and 18 to 65 years of age in clinical remission with a Crohns Disease Activity Index (CDAI) score of 150 or less, with symptoms of functional BAM or symptoms of BAM after small bowel resection with a frequency of at least 3 to maximal 15 liquid or soft stools per day. Stable medical treatment of CD for a minimal period of 3 months preceding the screening visit, consisting of either continuous oral treatment of aminosalicylate, prednisolone (a maximum 10 mg/day), azathioprine, 6-mercaptopurine, or methotrexate or supporting periodic treatment* with TNF-alpha AK (Infliximab, Adalimumab, Certolizumab) (for patients on TNF-alpha, dosing with TNF-alpha should coincide with baseline visit) Blood serum CRP value of less or equal then 1 mg/dl (10 mg/l). BAM assessed with a blood test on a 7α-hydroxy-4-cholesten-3-on excretion of equal or more than 50 ng/ml Exclusion criteria: Allergy or hypersensitivity to any of the components of cholestagel or placebo as identified from the medical history Participation at another clinical trial within a period of 4 weeks before the screening visit Presence of any addiction, alcohol abuse or specific disease that would not allow the patient to understand the essence and requirements and potential consequences of the participation to the clinical trial Signs suggestive of the patient being unable to follow the visit schedule as required (for example for professional obligations) Treatment with cyclosporine, or tacrolimus, 3 month or less before screening Oral Treatment with antibiotics 3 weeks or less before screening Topical treatment with steroid- or mesalazine-containing applications 3 weeks or less before screening Treatment with bile acid bile acid binding agent (e.g. Cholestayramine)6 weeks or less before screening Infectious diseases (HIV, hep B, hep C, tuberculosis, listeriosis, positive clostridium-difficile-toxin- proof in faeces) Current presence of intra-abdominal abscess or Fistula Cholestatic liver disease, bowel or biliary obstruction Dysphagia or swallowing disorders Known malignancy or history of malignancy Having undergone intestinal surgery within 6 months from screening Status after intestinal surgery with more then 100cm of resected bowel. Short bowel syndrome Planned -gastrostomy, ileostomy or colostomy. Pregnancy and lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo tablet: 3 times daily 2 tablets<br>|
| Active Comparator: Cholestagel<br> | Drug: Colesevelam<br>* Colesevelam 625 mg tablet; 3 times daily 2 tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of fluid stool > 30 % |  | 4 weeks after baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of Stool Consistency | Proportion of patients on cholestagel compared to placebo that reaches improvement of stool consistency on the Bristol stool chart of at least one point. | 4 weeks after baseline | 
| Improvement of Quality of Life. | Proportion of patients on cholestagel compared to placebo that reaches an improvement of the Quality of Life. | 4 weeks after baseline | 
| Change of median liquid or soft stool frequency/per day. |  | 4 weeks after baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colesevelam, IBD, Bile Acid Malabsorption, Crohns disease