Metabolic Effects of Endogenous Bile Acids After Gastric Bypass Surgery

NCT ID: NCT06925997

Last Updated: 2025-04-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-02
• Study Completion Date: 2028-12-31

Brief Summary

Non-randomized, open-label, parallel-group clinical study evaluating the effects of endogenous bile acids on changes in plasma fibroblast growth factor-19 (FGF-19) and glucose metabolism by extended depletion of circulating bile acids using colesevelam as an experimental tool in subjects operated with gastric by-pass (RYGB).

Detailed Description

The study design consists of 4 study visits, two performed before (V1 at day -7 and V2 at day 0 relative to initiation colesevelam treatment) and two after approximately 8 weeks of colesevelam treatment (V3 at day 49 and V4 at day 56). Biometrics, fasting blood samples and a standard mixed meal test are performed at V2 and V4. 75Se-HCAT scintigraphy is carried out between V1 to V2 and V3 to V4, respectively. Between V2 and V3 the subjects will have two telephone calls and one visit at the Endocrine Research Unit for fasting blood samples to make sure they do not experience any adverse events and are compliant.

The control groups will only participate in V1 and V2. The aim with the control groups is to have baseline values for unoperated subjects with and without diabetes to compare with the values in the intervention group after 8 weeks of depletion of endogenous bile acids.

Conditions

Bariatric Surgery Candidate; Bile Acid, Elevated Serum; Glucose Metabolism Disorders

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

3.75 mg Colesevelam in 8 weeks

Group Type: EXPERIMENTAL

Colesevelam

Intervention Type: DRUG

Colesevelam is an approved drug with well known adverse events. Gastrointestinal side effects (Obstipation, flatulence, abdominal pain, diarrhea, nausea, meteorism, vomiting, chanced faeces) are very common (\>10%) or common (1-10%), but are mild and tolerable in most cases. All participants will be monitored closely, and colesevelam will be discontinued if the subject experience unreserved adverse events. All effects of colesevelam are transient (17-19) as the compound is not absorbed to the systemic circulation, i.e. treatment effects cease when the drug is excreted from the intestine. Specifically, no permanent metabolic effects of colesevelam has been observed in crossover experiments (27). Therefore, 8 weeks of colesevelam treatment as planned in the current study will have no long lasting positive or negative effects on the participants.

Interventions

Colesevelam

Colesevelam is an approved drug with well known adverse events. Gastrointestinal side effects (Obstipation, flatulence, abdominal pain, diarrhea, nausea, meteorism, vomiting, chanced faeces) are very common (\>10%) or common (1-10%), but are mild and tolerable in most cases. All participants will be monitored closely, and colesevelam will be discontinued if the subject experience unreserved adverse events. All effects of colesevelam are transient (17-19) as the compound is not absorbed to the systemic circulation, i.e. treatment effects cease when the drug is excreted from the intestine. Specifically, no permanent metabolic effects of colesevelam has been observed in crossover experiments (27). Therefore, 8 weeks of colesevelam treatment as planned in the current study will have no long lasting positive or negative effects on the participants.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Intervention group

• RYGB-operated ≥ 18 months prior to inclusion
• History of diabetes prior to RYGB (HbA1c ≥48 mmol/mol or use of antidiabetic medication)
• HbA1c <58 mmol/mol on no antidiabetic medication or metformin alone
• Weight change < ±3 kg for >3 months at time of inclusion

Control group A

• No history of diabetes
• HbA1c <48 mmol/mol at time of inclusion
• Fasting plasma glucose < 7.0 mmol/L at time of inclusion
• Weight change < ±3 kg for >3 months at time of inclusion Control group B
• Type 2 diabetes (HbA1c ≥48 mmol/mol or use of antidiabetic medication at time of inclusion)
• Weight change < ±3 kg for >3 months at time of inclusion

Exclusion Criteria

• Pregnancy or breastfeeding
• Haemoglobin < 6.5 mmol/L at time of inclusion
• Fasting plasma glucose > 10.0 mmol/L at time of inclusion
• Prior cholecystectomy
• Chronic or tendency to diarrhoea

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hvidovre University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Marie-Louise Dichman

Principal investigator, MD, Ph.D. student

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Medicine, Copenhagen University Hospital - Amager and Hvidovre

Hvidovre, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Marie-Louise Dichman

Role: CONTACT

marie-louise.dichman@regionh.dk

+4526710371

Carsten Dirksen

Role: CONTACT

carsten.dirksen@regionh.dk

Facility Contacts

Marie-Louise Dichman

Role: primary

marie-louise.dichman@regionh.dk

+4526710371

Carsten Dirksen

Role: backup

carsten.dirksen@regionh.dk

Other Identifiers

H-22041713

Identifier Type: -

Identifier Source: org_study_id