Protocol for a randomised, double-blinded, placebo-controlled, double-dummy 6-week clinical trial comparing the treatment effects of the glucagon-like peptide 1 receptor agonist liraglutide versus the bile acid sequestrant colesevelam on bile acid malabsorption

IntroductionBile acid malabsorption (BAM) is a socially debilitating disease characterised by high stool frequency and urgency caused by a spillover of bile acids into the colon. Bile acid sequestrants (BASs) have limited therapeutic effect but represent the only available treatment option. Cases reporting total remission of BAM-related symptoms after treatment with liraglutide, a glucagon-like peptide 1 analogue, prompted us to design a clinical trial investigating the therapeutic effect of this compound in patients with BAM.Methods and analysisFifty adult individuals with moderate or severe BAM as assessed by the 75selenium-homotaurocholic acid test (SeHCAT) will, after a run-in period of 10 days with no BAM treatment, be randomised to either treatment with the BAS colesevelam or liraglutide (double blinded) for 6 weeks. Daily symptom diaries and questionnaires will be filled in. Blood and faecal samples will be collected and SeHCAT will be performed at baseline, after week 3 and at end of trial. The primary endpoint is change in daily stool frequency. Secondary endpoints include changes from baseline in questionnaires, biochemistry, SeHCAT and faecal bile acid content and microbial composition.Ethics and disseminationThe study complies with Danish and European Union legislation and is approved by the Danish Medicines Agency, the Regional Scientific Ethics Committee of the Capital Region of Denmark and the Danish Data Protection Agency. The study is monitored by the Capital Region of Denmark’s good clinical practice unit. All results, positive, negative and inconclusive, will be disseminated at national and/or international scientific meetings and in peer-reviewed scientific journals.Trial registration numberEudraCA: 2018-003575-34; Pre-results.

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Remission of Bile Acid Malabsorption Symptoms Following Treatment With the Glucagon-Like Peptide 1 Receptor Agonist Liraglutide

Gastroenterology ◽

10.1053/j.gastro.2019.04.002 ◽

2019 ◽

Vol 157 (2) ◽

pp. 569-571

Author(s):

Martin L. Kårhus ◽

Andreas Brønden ◽

Michael E. Røder ◽

Salvatore Leotta ◽

David P. Sonne ◽

...

Keyword(s):

Bile Acid ◽

Receptor Agonist ◽

Bile Acid Malabsorption ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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103-OR: The Glucagon-Like Peptide-1 Analog, Liraglutide Is a Safe and Effective Treatment of Bile Acid Malabsorption: A Proof of Concept Study

Diabetes ◽

10.2337/db21-103-or ◽

2021 ◽

Vol 70 (Supplement 1) ◽

pp. 103-OR

Author(s):

MARTIN L. KÅRHUS ◽

ANDREAS BRØNDEN ◽

JULIE FORMAN ◽

ANNE HAABER ◽

EBBE LANGHOLZ ◽

...

Keyword(s):

Bile Acid ◽

Effective Treatment ◽

Proof Of Concept ◽

Concept Study ◽

Bile Acid Malabsorption ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Does glucagon-like peptide-1 (GLP-1) receptor agonist stimulation reduce alcohol intake in patients with alcohol dependence: study protocol of a randomised, double-blinded, placebo-controlled clinical trial

BMJ Open ◽

10.1136/bmjopen-2017-019562 ◽

2018 ◽

Vol 8 (7) ◽

pp. e019562 ◽

Cited By ~ 7

Author(s):

Kerstin K Antonsen ◽

Mette K Klausen ◽

Amanda S Brunchmann ◽

Nina le Dous ◽

Mathias E Jensen ◽

...

Keyword(s):

Clinical Trial ◽

Alcohol Consumption ◽

Alcohol Dependence ◽

Medical Treatment ◽

Receptor Agonist ◽

Major Public Health Problem ◽

Study Results ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Double Blinded

IntroductionAlcohol dependence is a major public health problem. It is underdiagnosed and undertreated. Even when treated, more than 2/3 of patients in abstinence-oriented treatment will relapse within the first year. Thus, there is an urgent need for efficacious medical treatment of alcohol dependence. Glucagon-like peptide-1 (GLP-1) receptor stimulation has proven to reduce alcohol consumption in preclinical experiments. However, the effect of GLP-1 receptor agonists in humans has to our knowledge, not yet been investigated.Methods and analysisDesign, participants and intervention: The effect of the once-weekly GLP-1-receptor-agonist exenatide will be investigated in a double-blinded, placebo-controlled, randomised clinical trial. 114 outpatients will be recruited and randomised to treatment with either placebo or exenatide once weekly for 26 weeks as a supplement to cognitive–behavioural therapy.The primary endpointis reduction in number of ‘heavy drinking days’.The secondary endpointsinclude changes in total alcohol consumption, days without consumption, changes in brain activity and function, smoking status, cognition, measures of quality of life and changes in phosphatidylethanol as a biomarker of alcohol consumption from baseline to follow-up at week 26.Status: Currently recruiting patients.Ethics and disseminationEthical approval has been obtained. Before screening, all patients will be provided oral and written information about the trial. The study results will be disseminated by peer-review publications and conference presentations and has the potential to reveal a completely new medical treatment of alcohol dependence.

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Single-Dose Metformin Enhances Bile Acid–Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2017-01091 ◽

2017 ◽

Vol 102 (11) ◽

pp. 4153-4162 ◽

Cited By ~ 13

Author(s):

Andreas Brønden ◽

Anders Albér ◽

Ulrich Rohde ◽

Jens F Rehfeld ◽

Jens J Holst ◽

...

Keyword(s):

Type 2 Diabetes ◽

Single Dose ◽

Bile Acid ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Bile acid supplementation improves established liver steatosis in obese mice independently of glucagon-like peptide-1 secretion

Journal of Physiology and Biochemistry ◽

10.1007/s13105-014-0336-1 ◽

2014 ◽

Vol 70 (3) ◽

pp. 667-674 ◽

Cited By ~ 10

Author(s):

Pablo Quintero ◽

Margarita Pizarro ◽

Nancy Solís ◽

Juan Pablo Arab ◽

Oslando Padilla ◽

...

Keyword(s):

Bile Acid ◽

Liver Steatosis ◽

Obese Mice ◽

Acid Supplementation ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Differences Between Randomized Clinical Trial Patients and Real-World Initiators of the Glucagon-Like Peptide 1 Receptor Agonist Liraglutide

Diabetes Care ◽

10.2337/dc18-0999 ◽

2018 ◽

Vol 41 (9) ◽

pp. e133-e135 ◽

Cited By ~ 8

Author(s):

Jakob Schöllhammer Knudsen ◽

Reimar Wernich Thomsen ◽

Anton Pottegård ◽

Filip Krag Knop ◽

Henrik Toft Sørensen

Keyword(s):

Clinical Trial ◽

Randomized Clinical Trial ◽

Real World ◽

Receptor Agonist ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Policaptil Gel Retard Intake Reduces Postprandial Triglycerides, Ghrelin and Appetite in Obese Children: A Clinical Trial

Nutrients ◽

10.3390/nu12010214 ◽

2020 ◽

Vol 12 (1) ◽

pp. 214

Author(s):

Elena Fornari ◽

Anita Morandi ◽

Claudia Piona ◽

Mara Tommasi ◽

Massimiliano Corradi ◽

...

Keyword(s):

Clinical Trial ◽

Area Under The Curve ◽

Obese Children ◽

Double Blind ◽

Postprandial Period ◽

Postprandial Triglycerides ◽

Double Blind Clinical Trial ◽

Affect Body Weight ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

The aim of this study is to test the hypothesis that the intake of Policaptil Gel Retard® (PGR) is able to affect appetite, metabolic and hormonal postprandial profile in obese children. 46 obese children were randomly assigned to treatment with PGR or placebo, in a double blind clinical trial. Two PGR tablets or placebo were given in fasting condition, before the ingestion of a mixed meal (15 kcal/kg lean body mass). Blood samples were taken at baseline and for 4 h, for measuring blood lipids, glucose, insulin, ghrelin, and glucagon like peptide-1 (GLP-1). Appetite was quantified using a visual analog scale. Children assuming PGR had a significantly lower increase of postprandial triglycerides (area under the curve (AUC): 3021 (2879) vs. 5038 (3738) mg × 240 min/Dl) and appetite (−234 (274) vs. 36 (329)) than children assuming placebo. The AUC of ghrelin was significantly lower after PGR ingestion, than after placebo (−8179 (8073) vs. −2800 (7579) pg × 240 min/mL). Blood glucose, insulin, non-esterified fatty acids (NEFA) and GLP-1 profiles were not significantly different in the two groups. In conclusion, a single intake of two tablets of PGR was associated with a significant reduction of appetite, ghrelin, and triglycerides in the postprandial period in obese children. Further investigation will assess if a chronic intake of PGR may affect body weight and glucose metabolism.

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