Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02810132
Recruitment Status : Completed
First Posted : June 22, 2016
Last Update Posted : April 20, 2018
Sponsor:
Information provided by (Responsible Party):
Henrik Wiggers, Aarhus University Hospital

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.


Condition or disease Intervention/treatment Phase
Heart Failure, Systolic Drug: Metformin Drug: Placebo Phase 2

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 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Metformin Treatment on Myocardial Efficiency in Patients With Heart Failure: A Randomized, Double-blind, Placebo-controlled Study
Actual Study Start Date : January 20, 2017
Actual Primary Completion Date : February 14, 2018
Actual Study Completion Date : February 14, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Active Comparator: Metformin
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
See above
Other Name: Glucophage XR 500

Placebo Comparator: Placebo
Drug: Placebo
Drug: Placebo
See above




Primary Outcome Measures :
  1. Changes in LV myocardial efficiency [ Time Frame: Baseline and 3 months ]
    LV myocardial efficiency is the ratio between stroke work and myocardial oxygen consumption, which are measured with echocardiography and [11C]-acetate PET.


Secondary Outcome Measures :
  1. Left ventricular global longitudinal strain during peak exercise [ Time Frame: Baseline and 3 months ]
  2. Myocardial oxygen consumption [ Time Frame: Baseline and 3 months ]
  3. Myocardial perfusion at rest [ Time Frame: Baseline and 3 months ]
  4. LV myocardial function evaluated by LVEF and diastolic function [ Time Frame: Baseline and 3 months ]
  5. LV mass [ Time Frame: Baseline and 3 months ]
  6. 6 minute walking distance [ Time Frame: Baseline and 3 months ]
  7. Changes in body composition [ Time Frame: Baseline and 3 months ]
    Measured by bioelectrical impedance analysis (BIA)

  8. Maximum oxygen consumption [ Time Frame: Baseline and 3 months ]
  9. Degree of insulin resistance [ Time Frame: Baseline and 3 months ]
  10. Minnesota living with heart failure questionnaire [ Time Frame: Baseline and 3 months ]
  11. NT-proBNP [ Time Frame: Baseline and 3 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02810132


Locations
Layout table for location information
Denmark
Aarhus University Hospital, Department of Cardiology, Palle Juul-Jensens Boulevard 99
Aarhus N, Denmark, 8200
Sponsors and Collaborators
Aarhus University Hospital
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Henrik Wiggers, Senior consultant, associate professor, PhD, DMSc, Aarhus University Hospital
ClinicalTrials.gov Identifier: NCT02810132    
Other Study ID Numbers: 2015-588
First Posted: June 22, 2016    Key Record Dates
Last Update Posted: April 20, 2018
Last Verified: April 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Heart Failure
Heart Failure, Systolic
Heart Diseases
Cardiovascular Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs