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

NCT02810132 | Completed Phase 2

• 1 other identifier: 2015-588
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Heart Failure, Systolic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Left ventricular global longitudinal strain during peak exercise

  Baseline and 3 months

• Myocardial oxygen consumption

  Baseline and 3 months

• Myocardial perfusion at rest

  Baseline and 3 months

• LV myocardial function evaluated by LVEF and diastolic function

  Baseline and 3 months

• LV mass

  Baseline and 3 months

Study Arms (2)

Metformin

ACTIVE COMPARATOR

Drug: Metformin Target dose: 1000 mg x 2 (if eGFR 30-60 ml/min: 500 mg x 2) Other name: Glucophage XR 500

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Drug: Placebo

Interventions

Metformin DRUG

See above

Also known as: Glucophage XR 500

Metformin

Placebo DRUG

See above

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• HbA1c 5.5 - 6.4% (37 - 47 mmol/mol) within the last 12 months prior to enrolment
• Impaired fasting glucose (IFG): Fasting P-glucose 5.6 - 6.9 mmol/l within 12 months prior to enrolment (patient in stable condition)
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Aarhus University Hospital: lead

Study Sites (1)

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

Aarhus N, 8200, Denmark

Location

Related Publications (1)

• Larsen AH, Wiggers H, Dollerup OL, Jespersen NR, Hansson NH, Frokiaer J, Brosen K, Norrelund H, Botker HE, Moller N, Jessen N. Metformin Lowers Body Weight But Fails to Increase Insulin Sensitivity in Chronic Heart Failure Patients without Diabetes: a Randomized, Double-Blind, Placebo-Controlled Study. Cardiovasc Drugs Ther. 2021 Jun;35(3):491-503. doi: 10.1007/s10557-020-07050-5. Epub 2020 Aug 8.

  PMID: 32770520 DERIVED

MeSH Terms

Conditions

Heart Failure, Systolic

Interventions

Metformin

Condition Hierarchy (Ancestors)

Heart Failure; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior consultant, associate professor, PhD, DMSc

Study Record Dates

• First Submitted: June 8, 2016
• First Posted: June 22, 2016
• Study Start: January 20, 2017
• Primary Completion: February 14, 2018
• Study Completion: February 14, 2018
• Last Updated: April 20, 2018

Record last verified: 2018-04

Locations

DK (1)