Clinical trial NCT06925997: Metabolic Effects of Endogenous Bile Acids After Gastric Bypass Surgery
Official title: Metabolic Effects of Endogenous Bile Acids After Gastric Bypass Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Bariatric Surgery Candidate
Bile Acid, Elevated Serum
Glucose Metabolism Disorders
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
First posted: 2025-04-13
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Glucose
timeFrame: 8 weeks
measure: FGF-19
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
measure: Explorative outcomes, glucose
timeFrame: 8 weeks
measure: Explorative outcomes, Bile acids
timeFrame: 8 weeks
measure: Explorative outcomes, FGF-19
timeFrame: 8 weeks
measure: Explorative outcomes, cholecystokinin (CCK)
timeFrame: 8 weeks
measure: Explorative outcomes, glucagon-like peptide-1 (GLP-1)
timeFrame: 8 weeks
measure: Explorative outcomes, Neurotensin
timeFrame: 8 weeks
measure: Explorative outcomes, triglycerides
timeFrame: 8 weeks
measure: Explorative outcomes, cholesterol
timeFrame: 8 weeks
measure: Explorative outcomes, C4 concentrations
timeFrame: 8 weeks
measure: Explorative outcomes, insulin sensitivity
timeFrame: 8 weeks
measure: Explorative outcomes, betal-cell function
timeFrame: 8 weeks
measure: Explorative outcomes, bile acid retention
timeFrame: 8 weeks
Locations:
city: Hvidovre
country: Denmark
facility: Department of Medicine, Copenhagen University Hospital - Amager and Hvidovre
Study officials:
References: