Metformin in Heart Failure Without Diabetes

• Status: Recruiting
• Trial end date: 2022-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Columbia University Medical Center is conducting 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.

Patients 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 assesment, exercise capacity, echocardiography, cardiac PET imaging and blood tests.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Columbia University
• Treatments: Metformin

Criteria

Inclusion Criteria:

• 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-D should be implanted, if indicated. Patients with a CRT device should be treated for > 3 months.

• Reduced ejection fraction defined as LVEF < 40%

• 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

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

• Negative urine-HCG for women of childbearing potential

Exclusion Criteria:

• Patients with diabetes or insulin resistant, defined as 1 or more of the following criteria:

1. HbA1c >6.0% within the last 12 months prior to enrollment

2. Impaired fasting insulin resistance index (HOMA-IR) >2.7

• Any oral or injectable hypoglycemic therapy (e.g. insulin, sulfonylureas)

• Recent Hospitalizations in the past 3 months

• Metformin treatment within the last 3 months

• eGFR below 45 in the prior 6 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, heart surgery, CRT implantation or other intervention during the study period that would potentially affect the function of the heart

• 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)

• Current abuse of alcohol or drugs

• Life-expectancy of less than 1 year due to co-existing morbid illness

• 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