Treatment of Bile Acid Malabsorption With Liraglutide (BAM-LIRA)

Comparing the effect of Liraglutide on bile acid malabsorption, with colesevelam

Study Overview

• Status: Completed
• Conditions: Bile Acid Malabsorption
• Intervention / Treatment: Drug: Liraglutide 6 MG/ML; Drug: Colesevelam

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Regionh
    • Hellerup, Regionh, Denmark, 2900
      • Gentofte Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Filip Krag Knop
• Collaborators: Herlev and Gentofte Hospital
• Investigators: Principal Investigator: Filip K Knop, MD PhD, filip.krag.knop.01@regionh.dk

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2019
• Primary Completion (Actual): March 10, 2021
• Study Completion (Actual): May 31, 2022

Study Registration Dates

• First Submitted: March 8, 2019
• First Submitted That Met QC Criteria: May 15, 2019
• First Posted (Actual): May 20, 2019

Study Record Updates

• Last Update Posted (Actual): June 3, 2022
• Last Update Submitted That Met QC Criteria: June 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Incretins; Liraglutide; Colesevelam Hydrochloride
• Other Study ID Numbers: H-18048247

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No