Metformin Pharmacokinetics in Patients With Chronic and Acute Heart Failure

NCT ID: NCT02797340

Last Updated: 2018-04-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-11
• Study Completion Date: 2018-04-30

Brief 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.

Detailed 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.

Conditions

Heart Failure, Systolic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Interventional

All participants

Group Type: EXPERIMENTAL

Blood draws and urine samples for metformin concentration measurements

Intervention Type: OTHER

Metformin

Intervention Type: DRUG

Interventions

Blood draws and urine samples for metformin concentration measurements

Intervention Type: OTHER

Metformin

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aarhus University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Henrik Wiggers

Senior consultant, associate professor, PhD, DMSc

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Aarhus University Hospital, Department of Cardiology, Palle Juul-Jensens Boulevard 99

Aarhus N, , Denmark

Countries

Denmark

Other Identifiers

50268-20150921

Identifier Type: -

Identifier Source: org_study_id