Metabolic Effects of Endogenous Bile Acids After Gastric Bypass Surgery (Bile-bar)

April 11, 2025 updated by: Marie-Louise Dichman, Hvidovre University Hospital
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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

18

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 3.75 mg Colesevelam in 8 weeks
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Glucose
Time Frame: 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).
8 weeks
FGF-19
Time Frame: 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).
8 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Explorative outcomes, glucose
Time Frame: 8 weeks
Plasma glucose concentration 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).
8 weeks
Explorative outcomes, Bile acids
Time Frame: 8 weeks
after 8 weeks of colesevelam-induced depletion of endogenous bile acids (V4) compared with baseline in the intervention group (V2).
8 weeks
Explorative outcomes, FGF-19
Time Frame: 8 weeks
after 8 weeks of colesevelam-induced depletion of endogenous bile acids (V4) compared with baseline in the intervention group (V2).
8 weeks
Explorative outcomes, cholecystokinin (CCK)
Time Frame: 8 weeks
after 8 weeks of colesevelam-induced depletion of endogenous bile acids (V4) compared with baseline in the intervention group (V2).
8 weeks
Explorative outcomes, glucagon-like peptide-1 (GLP-1)
Time Frame: 8 weeks
after 8 weeks of colesevelam-induced depletion of endogenous bile acids (V4) compared with baseline in the intervention group (V2).
8 weeks
Explorative outcomes, Neurotensin
Time Frame: 8 weeks
after 8 weeks of colesevelam-induced depletion of endogenous bile acids (V4) compared with baseline in the intervention group (V2).
8 weeks
Explorative outcomes, triglycerides
Time Frame: 8 weeks
after 8 weeks of colesevelam-induced depletion of endogenous bile acids (V4) compared with baseline in the intervention group (V2).
8 weeks
Explorative outcomes, cholesterol
Time Frame: 8 weeks
after 8 weeks of colesevelam-induced depletion of endogenous bile acids (V4) compared with baseline in the intervention group (V2).
8 weeks
Explorative outcomes, C4 concentrations
Time Frame: 8 weeks
after 8 weeks of colesevelam-induced depletion of endogenous bile acids (V4) compared with baseline in the intervention group (V2).
8 weeks
Explorative outcomes, insulin sensitivity
Time Frame: 8 weeks
Changes in Insulin sensitivity (HOMA-IR) after 8 weeks of colesevelam-induced depletion of endogenous bile acids (V4) compared with baseline in the intervention group (V2).
8 weeks
Explorative outcomes, betal-cell function
Time Frame: 8 weeks
Changes in Beta-cell function (disposition index) after 8 weeks of colesevelam-induced depletion of endogenous bile acids (V4) compared with baseline in the intervention group (V2).
8 weeks
Explorative outcomes, bile acid retention
Time Frame: 8 weeks
Changes in Insulin bile acid retention (75Se-HCAT) after 8 weeks of colesevelam-induced depletion of endogenous bile acids (V4) compared with baseline in the intervention group (V2).
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hvidovre University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 2, 2024

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

April 15, 2024

First Submitted That Met QC Criteria

April 11, 2025

First Posted (Actual)

April 13, 2025

Study Record Updates

Last Update Posted (Actual)

April 13, 2025

Last Update Submitted That Met QC Criteria

April 11, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-22041713

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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