Metformin Pharmacokinetics in Patients With Chronic and Acute Heart Failure

Heart Failure, Systolic Clinical Trial

— MetKin  

Official title:

Metformin in Patients With Chronic and Acute Heart Failure: Pharmacokinetics and Polymorphisms in Genes Encoding Membrane Metformin Transporter Proteins

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02797340
• Other study ID #: 50268-20150921
• Status: Active, not recruiting
• Phase: Phase 4
• First received: June 8, 2016
• Last updated: April 19, 2018
• Start date: January 11, 2016
• Est. completion date: April 30, 2018

Study information

• Verified date: April 2018
• Source: Aarhus University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study evaluates the pharmacokinetics of metformin in heart failure patients in acute and chronic state in relation to metformin transporter genotypes. Participants have heart failure and type 2 diabetes treated with metformin.

Hypothesis:

Primary: The renal clearance of metformin is decreased in acute state of congestive heart failure compared with chronic state.

Secondary: Metformin trough values in HF patients are influenced by polymorphisms in transporter genes relevant to the pharmacokinetics of metformin.

Description:

Background: Heart failure (HF) is a common disease and diabetes/insulin resistance are present in approximately 50 % of HF patients. Metformin is the most commonly prescribed oral anti-diabetic drug, and a huge inter-individual variability in trough steady-state metformin concentration in type 2 diabetics have been demonstrated. Genetic polymorphisms in metformin transporter genes are likely to have a direct impact on metformin pharmacokinetics and variability in drug responses, but the influence of polymorphisms in these transporter genes on circulating metformin levels is presently unknown in HF patients.

Objectives:

A) To compare the pharmacokinetics of metformin in 12 diabetic patients with HF in acute and chronic state.

B) To investigate the influence of polymorphisms in genes encoding the metformin transporter proteins on metformin trough levels in 150 diabetic HF patients.

Design: An open, single-center study enrolling 12 patients with acute heart failure (study A) and 150 patients with stable chronic heart failure (study B). The participants have diabetes already treated with metformin prior to inclusion. Through repeated blood draws, the concentration of metformin will be determined along with genotyping for metformin transporter genes.

Primary outcome:

Study A: Changes in renal clearance of metformin between patients with acute and chronic heart failure.

Study B: Mean trough steady-state concentrations of metformin with emphasis on the intra-interindividual variability in HF patients.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 110
• Est. completion date: April 30, 2018
• Est. primary completion date: April 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with heart failure

• LVEF < 45% within 12 months prior to inclusion

• NYHA-class I, II, III or IV

• Ability to understand the written patient information and to give informed consent

• Diabetes Type 2 (and in metformin treatment for > 1 month)

• Stable dosage of metformin treatment for at least 1 week prior to examination

Exclusion Criteria:

• Age < 18 years

• Current abuse of alcohol or drugs

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure, Systolic

Intervention

Other:
• Blood draws and urine samples for metformin concentration measurements

Drug:
• Metformin

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital, Department of Cardiology, Palle Juul-Jensens Boulevard 99	Aarhus N

Sponsors (1)

Lead Sponsor	Collaborator
Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in renal clearance of metformin between patients with acute and chronic heart failure.		approximately 2 weeks
Primary	Mean trough steady-state concentrations of metformin with emphasis on the intra-interindividual variability in HF patients		3 weeks