Treatment of Bile Acid Malabsorption With Liraglutide

Study Overview
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Brief Summary
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Comparing the effect of Liraglutide on bile acid malabsorption, with colesevelam

Detailed Description
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The overall objective of the present study is to provide proof of concept that treatment with the GLP-1 receptor agonist liraglutide is efficacious (as assessed by symptom relief, i.e. response to treatment) and safe (as assessed by adverse effects) in the management of BAM and that it improves bile acid reabsorption (as assessed by SeHCAT) in these patients.

Official Title
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Treatment of Bile Acid Malabsorption With Liraglutide

Conditions
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Bile Acid Malabsorption

Intervention / Treatment
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* Drug: Liraglutide 6 MG/ML
* Drug: Colesevelam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Caucasian ethnicity SeHCAT-verified moderate (5-10% bile acid retention after 7 days) or severe BAM (<5% retention) Normal haemoglobin (for men 8.3-10.5 mmol/L; for women 7.3-9.5 mmol/L) Age above 18 years and below 75 years Informed and written consent BMI >18,5 kg/m2 and <40 kg/m2 Glycated haemoglobin (HbA1c) <48 mmol/mol Exclusion Criteria: • History of or present hepatobiliary disorder (except for non-alcoholic steatotic liver disease) and/or alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >3 times upper limit of normal) or history of hepatobiliary disorder Gastrointestinal disease (except for BAM), previous intestinal resection or any major intra-abdomial surgery Diabetes mellitus Nephropathy with eGFR < 60 mL/min/1.73m2 Treatment with medicine that cannot be paused for 12 hours Hypothyroidism or hyperthyroidism, if not well regulated. Treatment with oral anticoagulants Active or recent malignant disease Any treatment or condition requiring acute or sub-acute medical or surgical intervention Females of child-bearing potential who is pregnant (tested before entering the study), breastfeeding or intend to become pregnant or is not using adequate contraceptive methods, which includes Intrauterine Device (IUD), birth control pills, sexual abstinence or living in a relationship with a sterile partner. Known or suspected hypersensitivity to trial products or related products Any condition considered incompatible with participation by the investigators

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Liraglutide/placebo-colesevelam<br>Liraglutide as active and colesevelam as placebo | Drug: Liraglutide 6 MG/ML<br>* Liraglutide as injections.<br>|
| Active Comparator: Placebo-Liraglutide/colesevelam<br>Liraglutide as placebo and colesevelam as placebo | Drug: Colesevelam<br>* 3 x 625 miligram 2 times a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in stool fequency | Contestants will use a questionaire, which will be filled out three times during the 7 weeks periode | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total symptoms score, quality of life scores, and biomarker. | Total symptoms score, quality of life scores, and biomarker values will be analysed using a constrained linear mixed model with inherent baseline adjustment and with an unstructured covariance pattern. Changes since baseline within and between groups will be reported with 95% confidence intervals. | 7 weeks | 
| Change in SeHCAT | Three SeHCAT scans will be made, and the difference will be evaluated | 7 weeks | 
| Proportions of patients tolerating the treatment and proportion of patients experiencing remission of BAM related diarrhoea | Proportions of patients tolerating the treatment and proportion of patients experiencing remission of BAM related diarrhoea within each group will be reported with exact binomial confidence intervals and compared between groups using risk differences and Fisher's exact test. | 7 weeks |