Metabolic Effects of Endogenous Bile Acids After Gastric Bypass Surgery

Early Phase 1

Recruiting

• Conditions: Bariatric Surgery Candidate; Bile Acid, Elevated Serum; Glucose Metabolism Disorders
• Interventions: Drug: Colesevelam

• Registration Number: NCT06925997
• Lead Sponsor: Hvidovre University Hospital

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.

Study Timeline

• Study First Submitted: 2024-04-15
• Study Start: 2024-05-02
• Status Verified: 2025-04
• Study First Submitted QC: 2025-04-11
• Last Update Submitted: 2025-04-11
• Study First Posted: 2025-04-13
• Last Update Posted: 2025-04-13
• Primary Completion: 2027-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 18

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
3.75 mg Colesevelam in 8 weeks	Colesevelam	-

Primary Outcome Measures

Name	Time	Method
Glucose	8 weeks	Changes in total areal under the curve (AUC) of plasma glucose concentrations during the mixed meal test after 8 weeks of colesevelam-induced depletion of endogenous bile acids (V4) compared with baseline in the intervention group (V2).
FGF-19	8 weeks	Changes in total AUC of plasma FGF-19 concentrations during the mixed meal test after 8 weeks of colesevelam-induced depletion of endogenous bile acids (V4) compared with baseline in the intervention group (V2).

Trial Locations

Locations (1)

Department of Medicine, Copenhagen University Hospital - Amager and Hvidovre; 🇩🇰 Hvidovre, Denmark