Heart FailurePhase 2Met-HeFTNCT03331861
Metformin in Heart Failure Without Diabetes
A Phase 2 study testing Metformin hydrochloride in people with Heart Failure, run by Columbia University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Metformin hydrochloride
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2019to 20 Aug 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
New York Hospital - Columbia University Irving Medical Center
New York, New York, 10032
About this study
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.
Read the 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.
- Conditions
- Heart Failure
- Being tested
- Metformin hydrochloride, Placebo
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin hydrochlorideDrug
Also called Metformin
Metformin starting at 500mg twice a day and increasing to 1000mg twice a day for a total of 6 months
PlaceboDrug
Also called Placebo Tablet
Similar dosing regime as active comparator
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | Metformin for 6 months Receives: Drug: Metformin hydrochloride |
| Placebo | Placebo comparator | Matched placebo for 6 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 6 months
Secondary outcomes (4)
Change in Visual Analog Scale (VAS) Score
Dyspnea Assessment. 100mm line scale ranging from 0 (worse imaginable breathing) to 100 (best imaginable breathing).
Measured: 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.
Measured: 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.
Measured: Baseline, 6 months
Heart Failure Hospitalizations
The number of hospitalizations recorded during the study will be tallied.
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start15 Feb 2019
- Primary completion20 Aug 2021
- Study completion20 Aug 2021
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Barry Fine, Columbia University
- Investigators
- Barry Fine, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03331861
- Sponsor's protocol ID
- AAAR5389
- Acronym
- Met-HeFT
- Status last verified
- Jul 2024
- First submitted
- 1 Nov 2017
- Last updated
- 18 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin in Heart Failure Without Diabetes
- ClinicalTrials.gov ID
- NCT03331861
- Acronym / sponsor ID
- Met-HeFT / AAAR5389
- Conditions
- Heart Failure
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of funding
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- 15 Feb 2019 (actual)
- Primary completion
- 20 Aug 2021 (actual)
- Study completion
- 20 Aug 2021 (actual)
- First posted
- 6 Nov 2017 (actual)
- Results
- Posted 18 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: Metformin hydrochlorideMetformin for 6 months |
| Placebo | Placebo comparator | Drug: PlaceboMatched placebo for 6 months |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin hydrochlorideAlso: MetforminMetformin starting at 500mg twice a day and increasing to 1000mg twice a day for a total of 6 months | Drug | Metformin |
| PlaceboAlso: Placebo TabletSimilar dosing regime as active comparator | Drug | Placebo |
Primary outcome
Change in Minute Ventilation to Carbon Dioxide Production (VE/VCO2) Slope
Time frame: 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.
4 secondary outcomes
Change in Visual Analog Scale (VAS) Score
Time frame: Baseline and 6 months
Minnesota LIVING WITH HEART FAILURE Questionnaire (MLHFQ) Score
Time frame: Baseline, 6 months
Peak Myocardial Oxygen Consumption (VO2)
Time frame: Baseline, 6 months
Heart Failure Hospitalizations
Time frame: Up to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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HS235 Study in Overweight and Obese Participants With Combined Pre and Post-Capillary Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction
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Heart Failure Patient Management and Interventions Using Continuous Patient Monitoring Outside Hospitals and Real-world Data
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Multi-Scale Analysis of Phenotypes in Heart Failure (MAP-HEART)
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Real-world Effectiveness and Safety of Savagen (Sacubitril/Valsartan) in Malaysian HFrEF Patients
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barry Fine, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin hydrochloride in people with Heart Failure, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Minute Ventilation to Carbon Dioxide Production (VE/VCO2) Slope (time frame: Baseline and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2024.