Heart Failure
Conditions
Brief summary
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.
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.
Interventions
DRUGMetformin hydrochloride
Metformin starting at 500mg twice a day and increasing to 1000mg twice a day for a total of 6 months
DRUGPlacebo
Similar dosing regime as active comparator
Sponsors
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Minute Ventilation to Carbon Dioxide Production (VE/VCO2) Slope | Baseline and 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visual Analog Scale (VAS) Score | Baseline and 6 months | Dyspnea Assessment. 100mm line scale ranging from 0 (worse imaginable breathing) to 100 (best imaginable breathing). |
| Minnesota LIVING WITH HEART FAILURE Questionnaire (MLHFQ) Score | Baseline, 6 months | 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. |
| Peak Myocardial Oxygen Consumption (VO2) | Baseline, 6 months | Oxygen consumption (VO2) (ml/min) will be measured on a breath by breath basis. Peak VO2 will be computed using standard methods. |
| Heart Failure Hospitalizations | Up to 6 months | The number of hospitalizations recorded during the study will be tallied. |
Countries
United States
Participant flow
Pre-assignment details
2 out of 6 participants screen failed and no further information was collected or analyzed.
Participants by arm
| Arm | Count |
|---|---|
| Metformin Metformin for 6 months
Metformin hydrochloride: Metformin starting at 500mg twice a day and increasing to 1000mg twice a day for a total of 6 months | 2 |
| Placebo Matched placebo for 6 months
Placebo: Similar dosing regime as active comparator | 2 |
| Total | 4 |
Baseline characteristics
| Characteristic | Metformin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United States | 2 participants | 2 participants | 4 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 0 / 2 | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 |
Outcome results
Primary
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.
Time frame: Baseline and 6 months
Population: Study was terminated early; data was not collected due to low enrollment, thus cannot be analyzed.
Secondary
Change in Visual Analog Scale (VAS) Score
Dyspnea Assessment. 100mm line scale ranging from 0 (worse imaginable breathing) to 100 (best imaginable breathing).
Time frame: Baseline and 6 months
Population: Study was terminated early; data was not collected due to low enrollment, thus cannot be analyzed.
Secondary
Heart Failure Hospitalizations
The number of hospitalizations recorded during the study will be tallied.
Time frame: Up to 6 months
Population: Study was terminated early; data was not collected due to low enrollment, thus cannot be analyzed.
Secondary
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.
Time frame: Baseline, 6 months
Population: Study was terminated early; data was not collected due to low enrollment, thus cannot be analyzed.
Secondary
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.
Time frame: Baseline, 6 months
Population: Study was terminated early; data was not collected due to low enrollment, thus cannot be analyzed.