Effects of Metformin Treatment on Myocardial Efficiency in Patients With Heart Failure

Heart Failure, Systolic Clinical Trial

— METRONOME  

Official title:

Effects of Metformin Treatment on Myocardial Efficiency in Patients With Heart Failure: A Randomized, Double-blind, Placebo-controlled Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02810132
• Other study ID #: 2015-588
• Status: Completed
• Phase: Phase 2
• First received: June 8, 2016
• Last updated: April 19, 2018
• Start date: January 20, 2017
• Est. completion date: February 14, 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 effects of metformin treatment on myocardial efficiency in heart failure patients. 36 patients will be randomized to three months of metformin or placebo treatment in addition to their regular therapy.

Hypothesis: Treatment with metformin in patients with heart failure has direct or indirect beneficial effects on left ventricular myocardial oxidative metabolism, myocardial efficiency and contractile function.

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 registry and experimental studies show beneficial effects of metformin in HF, but randomized trials are needed.

Objectives: To investigate if treatment with metformin in patients with HF has beneficial effects on myocardial efficiency,

Design: A randomized, double-blind, placebo-controlled, single-center design. 36 patients with systolic heart failure will be randomized to either metformin (N = 18) or placebo (N= 18) for 3 months.

Methods: Patients will undergo echocardiography at rest and during exercise along with [11C]-acetate PET.

Primary outcome parameter is changes in myocardial external efficiency from visit 1 to 3 months of therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: February 14, 2018
• Est. primary completion date: February 14, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with chronic heart failure uptitrated to recommended or maximally tolerated dose of ACE-I/ARB (unless contraindicated) and beta-blocker (unless contraindicated). If indicated, an aldosterone receptor antagonist should be given (unless contraindicated). An ICD and/or CRT should be implanted, if indicated. Patients with a CRT device should be treated for > 3 months.

• LVEF < 45%

• NYHA-class II, III or IV

• Relatively preserved renal function (eGFR > 30 ml/min)

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

• Negative urine-HCG for women of childbearing potential

• Patients must have insulin resistance, defined as 1 or more of the following criteria:

1. HbA1c 5.5 - 6.4% (37 - 47 mmol/mol) within the last 12 months prior to enrolment

2. Impaired fasting glucose (IFG): Fasting P-glucose 5.6 - 6.9 mmol/l within 12 months prior to enrolment (patient in stable condition)

3. Impaired glucose tolerance (IGT) if OGTT has been performed at any time prior to enrolment: Fasting P-glucose < 7.0 mmol/l and 2 hour P-glucose 7.8 -11.0 mmol/l

Exclusion Criteria:

• Metformin treatment within the last 3 months

• Known allergy to metformin or major side effects to metformin treatment

• Acute myocardial infarction, unstable angina or revascularization < 3 months at the time of randomization

• Planned coronary revascularization

• Significant, uncorrected cardiac valve disease

• Cardiac arrest or life threatening ventricular arrhythmias within the last 3 months (unless treated with an ICD)

• Atrial fibrillation with poorly controlled ventricular rate at rest (> 100 beats/min)

• Hypertrophic or restrictive cardiomyopathy, infiltrative or storage myocardial disease, active myocarditis, or pericardial disease.

• Planned major surgery

• Female patients who are pregnant, nursing, or of childbearing potential while not practicing effective chemical contraceptive methods (i.e. oral, implanted, injectable, or transdermal contraceptive hormones; intrauterine device)

• Age < 18 years

• Current abuse of alcohol or drugs

• Cancer, with a life-expectancy of less than 2 years

• Stroke within the last 6 months

• Liver disease with P-ALAT >3 times upper normal limit (it is possible to repeat this measurement once within a month)

• Significant comorbidity or issue that makes the patient unsuitable for participation as judged by the investigator

• Participation in another study involving long-term medical intervention (participation in device studies is allowed)

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure, Systolic

Intervention

Drug:
• Metformin
See above
• Placebo
See above

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 LV myocardial efficiency	LV myocardial efficiency is the ratio between stroke work and myocardial oxygen consumption, which are measured with echocardiography and [11C]-acetate PET.	Baseline and 3 months
Secondary	Left ventricular global longitudinal strain during peak exercise		Baseline and 3 months
Secondary	Myocardial oxygen consumption		Baseline and 3 months
Secondary	Myocardial perfusion at rest		Baseline and 3 months
Secondary	LV myocardial function evaluated by LVEF and diastolic function		Baseline and 3 months
Secondary	LV mass		Baseline and 3 months
Secondary	6 minute walking distance		Baseline and 3 months
Secondary	Changes in body composition	Measured by bioelectrical impedance analysis (BIA)	Baseline and 3 months
Secondary	Maximum oxygen consumption		Baseline and 3 months
Secondary	Degree of insulin resistance		Baseline and 3 months
Secondary	Minnesota living with heart failure questionnaire		Baseline and 3 months
Secondary	NT-proBNP		Baseline and 3 months