Effect of Metformin and Cholecystokinin-mediated Gallbladder Emptying on GLP-1 Secretion in Type 2 Diabetes

NCT ID: NCT02497313

Last Updated: 2017-05-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-07-31

Study Completion Date

2016-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Accumulating evidence suggests that bile acids in our intestines may constitute essential components in the complex mechanisms regulating gut hormone secretion and glucose homeostasis. Thus, it is likely that modification of the enterohepatic circulation of bile acids can lead to changes in gut hormone secretion and consequently affect glucose homeostasis.

The current study is a human interventional randomized controlled cross-over study including four study days for each participant. Metformin will be applied as a tool to reduce bile acid reuptake in the small intestine; thereby increasing bile acid concentration in the more distal parts of the gut where GLP-1-secreting L cell are abundant. Interestingly, metformin has been shown to reduce the active reabsorption of bile acids in the ileum and cause increased faecal elimination of bile acids. Clinical data has suggested that metformin causes an increase in the postprandial secretion of GLP-1 in humans including patients with type 2 diabetes. Intravenous infusion of cholecystokinin will be used to elicit gallbladder contraction and emptying. The aim is to examine how (and if) modification of bile acid reabsorption can influence postprandial glucagon-like peptide-1 (GLP-1) secretion and glucose homeostasis in patients with type 2 diabetes.

The investigators hypothesize that higher luminal concentrations of bile acids in the distal gut will elicit changes in gut hormone secretion. The current study will help to clarify this hypothesis and improve our general understanding of the association between bile acid circulation and signalling, gut hormone secretion and glucose metabolism.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Diabetes Mellitus, Type 2

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Placebo+Placebo

Oral ingestion of metformin placebo combined with intravenous infusion of isotonic saline.

Group Type PLACEBO_COMPARATOR

Isotonic saline

Intervention Type DRUG

Metformin placebo

Intervention Type DRUG

Placebo+Cholecystokinin

Oral ingestion of metformin placebo combined with intravenous infusion of cholecystokinin.

Group Type ACTIVE_COMPARATOR

Metformin placebo

Intervention Type DRUG

Cholecystokinin

Intervention Type DRUG

Metformin+Placebo

Oral ingestion of metformin combined with intravenous infusion of isotonic saline.

Group Type ACTIVE_COMPARATOR

Isotonic saline

Intervention Type DRUG

Metformin

Intervention Type DRUG

Metformin+Cholecystokinin

Oral ingestion of metformin combined with intravenous infusion of cholecystokinin.

Group Type ACTIVE_COMPARATOR

Cholecystokinin

Intervention Type DRUG

Metformin

Intervention Type DRUG

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Isotonic saline

Intervention Type DRUG

Metformin placebo

Intervention Type DRUG

Cholecystokinin

Intervention Type DRUG

Metformin

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Type 2 diabetes for at least 3 months (diagnosed according to the criteria of the World Health Organization (WHO))
* Men and postmenopausal women
* Metformin applied as the only anti-diabetic drug
* Caucasian ethnicity
* Normal haemoglobin
* BMI \>23 kg/m2 and \<35 kg/m2
* Informed and written consent

Exclusion Criteria

* Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) \>2 times normal values) or history of hepatobiliary disorder
* Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery
* Nephropathy (serum creatinine \>150 µM and/or albuminuria)
* Hypo- and hyperthyroidism
* Hypo- and hypercalcaemia
* Hypo- and hyperphosphataemia
* Active or recent malignant disease
* Treatment with medicine that cannot be paused for 12 hours
* Treatment with oral anticoagulants
* Any treatment or condition requiring acute or sub-acute medical or surgical intervention
* Any condition considered incompatible with participation by the investigators
Minimum Eligible Age

40 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University Hospital, Gentofte, Copenhagen

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Andreas Brønden

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Andreas Brønden, MD

Role: PRINCIPAL_INVESTIGATOR

PhD student

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Center for Diabetes Research, Herlev-Gentofte Hospital

Hellerup, , Denmark

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Denmark

References

Explore related publications, articles, or registry entries linked to this study.

Bronden A, Alber A, Rohde U, Rehfeld JF, Holst JJ, Vilsboll T, Knop FK. Single-Dose Metformin Enhances Bile Acid-Induced Glucagon-Like Peptide-1 Secretion in Patients With Type 2 Diabetes. J Clin Endocrinol Metab. 2017 Nov 1;102(11):4153-4162. doi: 10.1210/jc.2017-01091.

Reference Type DERIVED
PMID: 28938439 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

H-15007280

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.