Metformin in Heart Failure Without Diabetes (Met-HeFT)

A pilot clinical research study that will assess the use of the medication metformin for heart failure in patients who are not diabetic and have no evidence of insulin resistance.

Study Overview

• Status: Terminated
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Metformin hydrochloride; Drug: Placebo

Detailed Description

Patients (n=50) will received either the study drug metformin or placebo for 4 months. During the study, the patients will undergo extensive testing that will include symptom assessment, exercise capacity, echocardiography, cardiac PET imaging and blood tests.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York Hospital - Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >18yrs old
• Patients with chronic heart failure (defined as >6 months duration) 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.
• Reduced ejection fraction defined as LVEF ≤ 35%
• NYHA-class II or III with stable symptoms for at least the past 3 months
• Renal Function by eGFR ≥ 45 ml/min (MDRD equation) in accordance with FDA guidance on metformin use in CKD(24)
• Non-insulin resistant defined as a fasting insulin resistance index, or HOMA-IR of <2.7.
• Non-diabetic defined as a HgbA1c <6.0

Exclusion Criteria:

• Any oral or injectable hypoglycemic therapy (e.g. insulin, sulfonylureas)
• Known allergy to metformin or major side effects to metformin treatment
• Concomitant use of a carbonic anhydrase inhibitor (such as acetazolamide or topirafmate)
• Heart Failure Hospitalizations in the past 3 months (primary diagnosis on admission is heart failure)
• Acute myocardial infarction, unstable angina or revascularization with prior 3 months at the time of randomization
• Planned coronary revascularization, heart surgery, CRT implantation or other intervention during the study period that would potentially affect the function of the heart
• Significant, uncorrected primary cardiac valve disease, specifically severely stenotic or regurgitant mitral or aortic valves
• 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 (> 110 beats/min)
• Hypertrophic or restrictive cardiomyopathy, infiltrative or storage myocardial disease, active myocarditis, or pericardial disease.
• Planned major surgery within the study period
• 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)
• Current abuse of alcohol or drugs
• Life-expectancy of less than 1 year due to co-existing morbid illness
• Liver disease with ALT or AST >3 times upper normal limit (it is possible to repeat this measurement once within a month)
• Advanced lung disease such as COPD
• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin; Metformin for 6 months	Drug: Metformin hydrochloride; Metformin starting at 500mg twice a day and increasing to 1000mg twice a day for a total of 6 months; Other Names: Metformin
Placebo Comparator: Placebo; Matched placebo for 6 months	Drug: Placebo; Similar dosing regime as active comparator; Other Names: Placebo Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Minute Ventilation to Carbon Dioxide Production (VE/VCO2) Slope	The VO2 change outcomes will be assessed for normality using standard visual assessments (Q-Q plots and histograms) and statistical tests (Kolmogorov-Smirnov). VE/VCO2 slope change will be calculated.	Baseline and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Visual Analog Scale (VAS) Score	Dyspnea Assessment. 100mm line scale ranging from 0 (worse imaginable breathing) to 100 (best imaginable breathing).	Baseline and 6 months
Minnesota LIVING WITH HEART FAILURE Questionnaire (MLHFQ) Score	A validated patient-oriented measure of the adverse effects of heart failure on a patient's life. The questionnaire is comprised of 21 questions around several physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. After receiving brief standardized instructions, the patient marks a 0 (zero) to 5 (five) scale to indicate the extent to which each itemized adversity of heart failure has prevented the patient from living as they wanted to live during the past 4 weeks. The questionnaire is simply scored by summation of all 21 responses.	Baseline, 6 months
Peak Myocardial Oxygen Consumption (VO2)	Oxygen consumption (VO2) (ml/min) will be measured on a breath by breath basis. Peak VO2 will be computed using standard methods.	Baseline, 6 months
Heart Failure Hospitalizations	The number of hospitalizations recorded during the study will be tallied.	Up to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin A1c		Baseline and 6 months
Serum Lactate		1 month and 6 months
Fasting Sugar	mg/dl	1 month and 6 months

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Barry Fine, MD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2019
• Primary Completion (Actual): August 20, 2021
• Study Completion (Actual): August 20, 2021

Study Registration Dates

• First Submitted: November 1, 2017
• First Submitted That Met QC Criteria: November 1, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): July 18, 2024
• Last Update Submitted That Met QC Criteria: July 17, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: AAAR5389

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes