Heart Failure, SystolicPhase 2METRONOMENCT02810132
Effects of Metformin Treatment on Myocardial Efficiency in Patients With Heart Failure
A Phase 2 study testing Metformin in people with Heart Failure, Systolic, run by Aarhus University Hospital at 1 site in Denmark.
Trial summary
The study evaluates the effects of metformin treatment on myocardial efficiency in heart failure patients. 36 patients will be randomized to three months of metformin or placebo treatment in addition to their regular therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Systolic
- What is being tested?
- Metformin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteDenmark
- Study dates
- 20 Jan 2017to 14 Feb 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with chronic heart failure 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.
- LVEF < 45%
- NYHA-class II, III or IV
- Relatively preserved renal function (eGFR > 30 ml/min)
- Ability to understand the written patient information and to give informed consent
- Negative urine-HCG for women of childbearing potential
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- Patients must have insulin resistance, defined as 1 or more of the following criteria:
- HbA1c 5.5 - 6.4% (37 - 47 mmol/mol) within the last 12 months prior to enrolment
- Impaired fasting glucose (IFG): Fasting P-glucose 5.6 - 6.9 mmol/l within 12 months prior to enrolment (patient in stable condition)
- Impaired glucose tolerance (IGT) if OGTT has been performed at any time prior to enrolment: Fasting P-glucose < 7.0 mmol/l and 2 hour P-glucose 7.8 -11.0 mmol/l
Who cannot join
- Metformin treatment within the last 3 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
- Significant, uncorrected cardiac valve disease
- Cardiac arrest or life threatening ventricular arrhythmias within the last 3 months (unless treated with an ICD)
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- 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)
- Age < 18 years
- Current abuse of alcohol or drugs
- Cancer, with a life-expectancy of less than 2 years
- 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
- Participation in another study involving long-term medical intervention (participation in device studies is allowed)
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Aarhus University Hospital, Department of Cardiology, Palle Juul-Jensens Boulevard 99
Aarhus N, 8200
About this study
Official title: Effects of Metformin Treatment on Myocardial Efficiency in Patients With Heart Failure: A Randomized, Double-blind, Placebo-controlled Study
The study evaluates the effects of metformin treatment on myocardial efficiency in heart failure patients. 36 patients will be randomized to three months of metformin or placebo treatment in addition to their regular therapy.
Hypothesis: Treatment with metformin in patients with heart failure has direct or indirect beneficial effects on left ventricular myocardial oxidative metabolism, myocardial efficiency and contractile function.
Read the detailed description
Background: Heart failure (HF) is a common disease and diabetes/insulin resistance are present in approximately 50 % of HF patients. Metformin is the most commonly prescribed oral anti-diabetic drug, and registry and experimental studies show beneficial effects of metformin in HF, but randomized trials are needed.
Objectives: To investigate if treatment with metformin in patients with HF has beneficial effects on myocardial efficiency,
Design: A randomized, double-blind, placebo-controlled, single-center design. 36 patients with systolic heart failure will be randomized to either metformin (N = 18) or placebo (N= 18) for 3 months.
Methods: Patients will undergo echocardiography at rest and during exercise along with [11C]-acetate PET.
Primary outcome parameter is changes in myocardial external efficiency from visit 1 to 3 months of therapy.
- Conditions
- Heart Failure, Systolic
- Being tested
- Metformin, Placebo
- Medical subject headings
- Heart Failure, Systolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glucophage XR 500
See above
PlaceboDrug
See above
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Active comparator | Drug: Metformin Target dose: 1000 mg x 2 (if eGFR 30-60 ml/min: 500 mg x 2) Other name: Glucophage XR 500 Receives: Drug: Metformin |
| Placebo | Placebo comparator | Drug: Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in LV myocardial efficiency
LV myocardial efficiency is the ratio between stroke work and myocardial oxygen consumption, which are measured with echocardiography and [11C]-acetate PET.
Measured: Baseline and 3 months
Secondary outcomes (11)
Left ventricular global longitudinal strain during peak exercise
Measured: Baseline and 3 months
Myocardial oxygen consumption
Measured: Baseline and 3 months
Myocardial perfusion at rest
Measured: Baseline and 3 months
LV myocardial function evaluated by LVEF and diastolic function
Measured: Baseline and 3 months
LV mass
Measured: Baseline and 3 months
6 minute walking distance
Measured: Baseline and 3 months
Changes in body composition
Measured by bioelectrical impedance analysis (BIA)
Measured: Baseline and 3 months
Maximum oxygen consumption
Measured: Baseline and 3 months
Degree of insulin resistance
Measured: Baseline and 3 months
Minnesota living with heart failure questionnaire
Measured: Baseline and 3 months
NT-proBNP
Measured: Baseline and 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2016 (estimated)
- Study start20 Jan 2017
- Primary completion14 Feb 2018
- Study completion14 Feb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Failure, SystolicStudies of the same condition, open and under way.
- More trials run by Aarhus University HospitalThe 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Henrik Wiggers, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02810132
- Sponsor's protocol ID
- 2015-588
- Acronym
- METRONOME
- Status last verified
- Apr 2018
- First submitted
- 8 Jun 2016
- Last updated
- 20 Apr 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Larsen AH, Wiggers H, Dollerup OL, Jespersen NR, Hansson NH, Frokiaer J, Brosen K, Norrelund H, Botker HE, Moller N, Jessen N. Metformin Lowers Body Weight But Fails to Increase Insulin Sensitivity in Chronic Heart Failure Patients without Diabetes: a Randomized, Double-Blind, Placebo-Controlled Study. Cardiovasc Drugs Ther. 2021 Jun;35(3):491-503. doi: 10.1007/s10557-020-07050-5. Epub 2020 Aug 8.
PubMed 32770520
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Metformin Treatment on Myocardial Efficiency in Patients With Heart Failure: A Randomized, Double-blind, Placebo-controlled Study
- ClinicalTrials.gov ID
- NCT02810132
- Acronym / sponsor ID
- METRONOME / 2015-588
- Conditions
- Heart Failure, Systolic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Aarhus University HospitalUniversity, hospital or other
- Study start
- 20 Jan 2017 (actual)
- Primary completion
- 14 Feb 2018 (actual)
- Study completion
- 14 Feb 2018 (actual)
- First posted
- 22 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study evaluates the effects of metformin treatment on myocardial efficiency in heart failure patients. 36 patients will be randomized to three months of metformin or placebo treatment in addition to their regular therapy.
Hypothesis: Treatment with metformin in patients with heart failure has direct or indirect beneficial effects on left ventricular myocardial oxidative metabolism, myocardial efficiency and contractile function.
Detailed description
Background: Heart failure (HF) is a common disease and diabetes/insulin resistance are present in approximately 50 % of HF patients. Metformin is the most commonly prescribed oral anti-diabetic drug, and registry and experimental studies show beneficial effects of metformin in HF, but randomized trials are needed.
Objectives: To investigate if treatment with metformin in patients with HF has beneficial effects on myocardial efficiency,
Design: A randomized, double-blind, placebo-controlled, single-center design. 36 patients with systolic heart failure will be randomized to either metformin (N = 18) or placebo (N= 18) for 3 months.
Methods: Patients will undergo echocardiography at rest and during exercise along with [11C]-acetate PET.
Primary outcome parameter is changes in myocardial external efficiency from visit 1 to 3 months of therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin | Active comparator | Drug: MetforminDrug: Metformin Target dose: 1000 mg x 2 (if eGFR 30-60 ml/min: 500 mg x 2) Other name: Glucophage XR 500 |
| Placebo | Placebo comparator | Drug: PlaceboDrug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients with chronic heart failure 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.
- LVEF < 45%
- NYHA-class II, III or IV
- Relatively preserved renal function (eGFR > 30 ml/min)
- Ability to understand the written patient information and to give informed consent
Key exclusion criteria (17 listed)
- Metformin treatment within the last 3 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
- Significant, uncorrected cardiac valve disease
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 |
|---|---|---|
| MetforminAlso: Glucophage XR 500See above | Drug | Metformin |
| PlaceboSee above | Drug | Placebo |
Primary outcome
Changes in LV myocardial efficiency
Time frame: Baseline and 3 months
LV myocardial efficiency is the ratio between stroke work and myocardial oxygen consumption, which are measured with echocardiography and [11C]-acetate PET.
11 secondary outcomes
Left ventricular global longitudinal strain during peak exercise
Time frame: Baseline and 3 months
Myocardial oxygen consumption
Time frame: Baseline and 3 months
Myocardial perfusion at rest
Time frame: Baseline and 3 months
LV myocardial function evaluated by LVEF and diastolic function
Time frame: Baseline and 3 months
LV mass
Time frame: Baseline and 3 months
6 minute walking distance
Time frame: Baseline and 3 months
Changes in body composition
Time frame: Baseline and 3 months
Maximum oxygen consumption
Time frame: Baseline and 3 months
Degree of insulin resistance
Time frame: Baseline and 3 months
Minnesota living with heart failure questionnaire
Time frame: Baseline and 3 months
NT-proBNP
Time frame: Baseline and 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2018.
- Derived from this study: PubMed 32770520Larsen AH, Wiggers H, Dollerup OL, Jespersen NR, Hansson NH, Frokiaer J, Brosen K, Norrelund H, Botker HE, Moller N, Jessen N. Metformin Lowers Body Weight But Fails to Increase Insulin Sensitivity in Chronic Heart Failure Patients without Diabetes: a Randomized, Double-Blind, Placebo-Controlled Study. Cardiovasc Drugs Ther. 2021 Jun;35(3):491-503. doi: 10.1007/s10557-020-07050-5. Epub 2020 Aug 8.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 in people with Heart Failure, Systolic, run by Aarhus University Hospital at 1 site in Denmark.
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 10 inclusion and 17 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: finished, as of the sponsor's last update on 20 Apr 2018. 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 Denmark. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Changes in LV myocardial efficiency (time frame: Baseline and 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02810132, which also lists 1 linked publication.
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 20 Apr 2018.