Metformin in Heart Failure Without Diabetes

Heart Failure Clinical Trial

— Met-HeFT  

Official title:

Metformin in Heart Failure Without Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03331861
• Other study ID #: AAAR5389
• Status: Recruiting
• Phase: Phase 2
• Start date: February 15, 2019
• Est. completion date: February 2022

Study information

• Verified date: March 2020
• Source: Columbia University
• Contact: Barry Fine, MD
• Phone: 212-305-5755
• Email: bmf2002[@]cumc.columbia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: February 2022
• Est. primary completion date: August 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Metformin hydrochloride
Metformin starting at 500mg twice a day and increasing to 1000mg twice a day for a total of 6 months
• Placebo
Similar dosing regime as active comparator

Locations

Country	Name	City	State
United States	New York Hospital - Columbia University Irving Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Columbia University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hemoglobin A1c		Baseline and 6 months
Other	Serum Lactate		1 month and 6 months
Other	Fasting Sugar	mg/dl	1 month and 6 months
Primary	Change in Minute Ventilation to Carbon Dioxide Production (VE/VCO2) Slope		Baseline and 6 months
Secondary	Change in Dyspnea Assesment Score	100mm Visual Analog Scale. 100mm line scale ranging from 0 (worse imaginable breathing) to 100 (best imaginable breathing)	Baseline and 6 months
Secondary	Minnesota Health Living with Heart Failure Questionnaire	Score	Baseline and 6 months
Secondary	Left Ventricular Function Evaluated by Ejection Fraction and Diastolic Function on Echocardiography		Baseline and 6 months
Secondary	Global Longitudinal Strain and Strain Rate Measured on Echocardiography		Baseline and 6 months
Secondary	B Type Natriuretic Peptide (BNP) level		Baseline and 6 months
Secondary	Body Weight	kg	Baseline and 6 months
Secondary	Peak Myocardial Oxygen Consumption (VO2)		Baseline and 6 months
Secondary	Quantitative 18F-FDG Activity in 9 Myocardial Segments	Glucose Metabolism	Baseline and 6 months
Secondary	Quantitative N13-NH3 Activity in 9 Myocardial Segments	Perfusion	Baseline and 6 months
Secondary	Heart Failure Hospitalizations	number	Over 6 months