Left Ventricular HypertrophyPhase 4MET-REMODELNCT02226510
MetfoRmin and Its Effects on Left Ventricular Hypertrophy in Normotensive Patients With Coronary Artery Disease
A Phase 4 study testing Metformin XL in people with Left Ventricular Hypertrophy and Insulin Resistance, run by University of Dundee at 1 site in United Kingdom.
Trial summary
Thickening of the heart muscle (left ventricle) known medically as Left Ventricular Hypertrophy (LVH) is very common in patients with heart disease. This increases risk of cerebrovascular/cardiovascular event. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Left Ventricular Hypertrophy, Insulin Resistance, Coronary Artery Disease
- What is being tested?
- Metformin XL
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Mar 2015to Dec 2017
- Phase
- Phase 4
- 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
- Aged 18 years or over
- Participant willing and able to give informed consent.
- Documented Ischaemic Heart Disease: either angio-graphically documented coronary artery disease or a previous history of myocardial infarction/angina.
- Screening echocardiography based diagnosis of LVH (LV mass indexed to height to the allometric power of 1.7; males > 81g/h1.7, females >60g/h1.7)
- Fasting insulin resistance index ≥ 2.7 AND/OR HbA1c >5.6 and less than 6.5 at screening
- Blood pressure < 140/85 mm Hg or 24hr BP <135/85 daytime average in screening
- Able (in the Investigators opinion) and willing to comply with all study requirements.
Who cannot join
- Cognitive impairment
- Type 1 or 2 Diabetes mellitus
- Chronic Heart Failure as evidenced by echocardiogram or documented diagnosis of CHF
- Left Ventricular Ejection Fraction <45% on screening echocardiography
- Contraindications to cardiac MRI (pacemakers, claustrophobia, metal implants, history of penetrative eye injury or exposure to metal fragments in eye requiring medical attention)
- Malignancy (receiving active treatment) or other life threatening disease, renal disease (CKD class 3B or worse)
Show all 9Show fewer
- Pregnancy/lactating females
- Any other reason considered inappropriate by a study physician
- Participants who have participated in any other clinical trial within the previous 30 days.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Ninewells Hospital & Medical School
Dundee, Angus, DD1 9SY
About this study
Official title: MetfoRmin and Its Effects on Myocardial Dimension and Left Ventricular Hypertrophy in Normotensive Patients With Coronary Artery Disease
Thickening of the heart muscle (left ventricle) known medically as Left Ventricular Hypertrophy (LVH) is very common in patients with heart disease. This increases risk of cerebrovascular/cardiovascular event.
LVH is asymptomatic and managed by the use of medication to control blood pressure, however LVH may be seen in normotensive patients where factors such as obesity and insulin resistance are present.
Read more
Insulin resistance is a condition where although the body produces insulin it is unable to utilize it effectively. Metformin, a drug used to treat diabetes, can reduce insulin resistance and cause weight loss, it may therefore improve LVH. This study will investigate the ability of metformin to reduce LVH in patients with heart disease, this may be a novel way forward in the risk reduction of cerebrovascular/cardiovascular events. Participants will be identified throughout NHS Tayside, those eligible will be randomly allocated to either metformin or a dummy medication (placebo) and will receive one year of treatment. At the beginning of the study, the thickness of the heart muscle will be measured by ultrasound scan and cardiac Magnetic Resonance Imaging (cMRI). We will also perform non-invasive tests to measure blood vessel function. These tests will be repeated after one year. At the end of the study, we will investigate the difference between placebo treatment and metformin treatment.
This study is funded by the British Heart Foundation.
Read the detailed description
This is a single centre trial designed to investigate the benefit, if any, of 12 month metformin XL 2000mg/day treatment on left ventricular hypertrophy (LVH) in 64 nondiabetic participants with Ischaemic heart disease (IHD) and insulin resistance (IR) and/or prediabetes.
Participants will be seen on seven occasions: screening, baseline/randomisation, 2 weeks post randomisation, month 1, month 4, month 8 and final month 12, during which vital signs and safety bloods will be performed. There will also be three telephone visits at: month 2, month 6 and month 10.
At a screening visit an initial history will be performed following informed consent. Participants will then undergo an echocardiogram (a painless ultrasound scan of the heart) in the Department of Clinical Pharmacology, Ninewells Hospital, Dundee. Blood pressure will be recorded and blood tests to determine fasting insulin resistance index (FIRI), prediabetes and routine safety, prior to metformin administration, will be performed.
Participants who meet all inclusion criteria will return for the randomisation visit within 4 weeks of screening where a Cardiac Magnetic Resonance Imaging (cMRI) scan will be performed followed by randomisation to either Metformin XL or placebo in a double blind, randomised fashion. Also, at this visit endothelial function tests will be performed to assess peripheral blood vessels in the forearm, central obesity will be quantified using waist circumference and waist to hip ratio (WHR) and study specific blood sampling performed (with participant consent).
At the final visit or early withdrawal the following will be performed: vital signs, safety bloods, study specific bloods (with participant consent), echocardiography, endothelial function tests and cMRI.
In the active arm, therapy will be metformin XL in an initial dose of 1000mg/day (metformin XL 500mg x2/day). Participants will continue on Metformin XL 500mg x2/day for two weeks, following safety blood checks this dose will be increased to 2000 mg/day. If the higher dose cannot be tolerated it will be reduced to 1000mg/day (or stopped if not tolerated).
The target dose of metformin XL at 2000mg/day was chosen based on a previous study of metformin in nondiabetic heart failure patients with IR, this study demonstrated a beneficial effect of metformin on insulin resistance, weight reduction and an improvement in submaximal exercise. The study used the immediate release form of metformin (target of 1000 mg x2/day) which was associated with significant gastrointestinal side effects resulting in 13% withdrawal of study medication. For this reason we have selected metformin XR due to improved gastrointestinal tolerability.
- Being tested
- Metformin XL, Placebo
- Medical subject headings
- Hypertrophy, Left Ventricular, Insulin Resistance, Coronary Artery Disease, Prediabetic State
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin XLDrug
Also called Diagemet XL
In the active arm, the added therapy will be metformin XL in an initial dose of 1000mg/day . They will continue on Metformin XL 500mg x2/day for 2 weeks and after safety blood checks the metformin XL dose will be increased to 2000 mg/day. If the higher dose cannot be tolerated the dose will be reduced to 1000mg/day.
PlaceboDrug
Placebo capsules (with an identical appearance to the active drug) containing only microcrystalline cellulose PhEur will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo capsules (with an identical appearance to the active drug) and containing only microcrystalline cellulose PhEur Receives: Drug: Placebo |
| Metformin XL | Active comparator | In the active arm, the added therapy will be metformin XL in an initial dose of 1000mg/day (metformin XL 500mg x2/day). They will continue on Metformin XL 500mg x2/day for two weeks and after safety blood checks the metformin XL dose will be increased to 2000 mg/day. If the higher dose cannot be tolerated the dose will be reduced to 1000mg/day (and stopped if this cannot be tolerated). Receives: Drug: Metformin XL |
What is being measured
The primary outcome is the main question the study is designed to answer.
Left Ventricular Mass Index
Cardiac magnetic resonance imaging will be performed at baseline and at 12 months, to measure Left Ventricular Mass Index in patients
Measured: 12 months
Secondary outcomes (9)
Central and Abdominal obesity
Abdominal magnetic resonance imaging will be performed at baseline and at 12 months to measure the changes in central and abdominal obesity
Measured: 12 months
Left Ventricular end systolic volume,
Cardiac magnetic resonance imaging will be performed at baseline and at 12 months to measure Left Ventricular end systolic volume
Measured: 12 months
Endothelial Function
Improvement in endothelial function with metformin compared with placebo, measured by FMD and PWA and skin reactive hyperaemia
Measured: 12 months
Insulin Resistance / Prediabetes
Improvement in insulin resistance (IR)/ prediabetes when treated with metformin compared to placebo in patients with IHD and IR measure using Fasting Insulin Resistance Index (FIRI)
Measured: 12 months
Inflammatory and other cardiovascular blood markers
Changes in inflammatory and other cardiovascular blood markers such as BNP/F2 Isoprostanes/oxi-LDL/Troponin T, when treated with metformin compared to placebo in patients with IHD and IR
Measured: 12 months
Number of participants with Adverse Event
Safety and efficacy of Metformin XL will be determined by monitoring changes from randomisation till the end of the study or so long the patient remains in the study, whichever is earlier.
Measured: 12 months
Left Ventricularend diastolic volume
Cardiac magnetic resonance imaging will be performed at baseline and at 12 months to measure Left Ventricular end diastolic volume
Measured: 12 months
Left Ventricular Ejection Fraction
Cardiac magnetic resonance imaging will be performed at baseline and at 12 months to measure Left Ventricular Ejection Fraction
Measured: 12 months
Left Ventricular Mass
Cardiac magnetic resonance imaging will be performed at baseline and at 12 months to measure Left Ventricular Mass
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2014 (estimated)
- Study startMar 2015
- Primary completionSep 2017
- Study completionDec 2017
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 Left Ventricular HypertrophyStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chim Lang, MD, Principal investigator, University of Dundee
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02226510
- Sponsor's protocol ID
- 2013CV08
- Other IDs
- 2014-003189-26, 14/ES/1061, 2014
- Acronym
- MET-REMODEL
- Status last verified
- Apr 2019
- First submitted
- 18 Aug 2014
- Last updated
- 10 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Mohan M, McSwiggan S, Baig F, Rutherford L, Lang CC. Metformin and its effects on myocardial dimension and left ventricular hypertrophy in normotensive patients with coronary heart disease (the MET-REMODEL study): rationale and design of the MET-REMODEL study. Cardiovasc Ther. 2015 Feb;33(1):1-8. doi: 10.1111/1755-5922.12101.
PubMed 25545400
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MetfoRmin and Its Effects on Myocardial Dimension and Left Ventricular Hypertrophy in Normotensive Patients With Coronary Artery Disease
- ClinicalTrials.gov ID
- NCT02226510
- Acronym / sponsor ID
- MET-REMODEL / 2013CV08
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Study start
- Mar 2015 (actual)
- Primary completion
- Sep 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 27 Aug 2014 (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.
Thickening of the heart muscle (left ventricle) known medically as Left Ventricular Hypertrophy (LVH) is very common in patients with heart disease. This increases risk of cerebrovascular/cardiovascular event.
LVH is asymptomatic and managed by the use of medication to control blood pressure, however LVH may be seen in normotensive patients where factors such as obesity and insulin resistance are present.
Insulin resistance is a condition where although the body produces insulin it is unable to utilize it effectively. Metformin, a drug used to treat diabetes, can reduce insulin resistance and cause weight loss, it may therefore improve LVH. This study will investigate the ability of metformin to reduce LVH in patients with heart disease, this may be a novel way forward in the risk reduction of cerebrovascular/cardiovascular events. Participants will be identified throughout NHS Tayside, those eligible will be randomly allocated to either metformin or a dummy medication (placebo) and will receive one year of treatment. At the beginning of the study, the thickness of the heart muscle will be measured by ultrasound scan and cardiac Magnetic Resonance Imaging (cMRI). We will also perform non-invasive tests to measure blood vessel function. These tests will be repeated after one year. At the end of the study, we will investigate the difference between placebo treatment and metformin treatment.
This study is funded by the British Heart Foundation.
Detailed description
This is a single centre trial designed to investigate the benefit, if any, of 12 month metformin XL 2000mg/day treatment on left ventricular hypertrophy (LVH) in 64 nondiabetic participants with Ischaemic heart disease (IHD) and insulin resistance (IR) and/or prediabetes.
Participants will be seen on seven occasions: screening, baseline/randomisation, 2 weeks post randomisation, month 1, month 4, month 8 and final month 12, during which vital signs and safety bloods will be performed. There will also be three telephone visits at: month 2, month 6 and month 10.
At a screening visit an initial history will be performed following informed consent. Participants will then undergo an echocardiogram (a painless ultrasound scan of the heart) in the Department of Clinical Pharmacology, Ninewells Hospital, Dundee. Blood pressure will be recorded and blood tests to determine fasting insulin resistance index (FIRI), prediabetes and routine safety, prior to metformin administration, will be performed.
Participants who meet all inclusion criteria will return for the randomisation visit within 4 weeks of screening where a Cardiac Magnetic Resonance Imaging (cMRI) scan will be performed followed by randomisation to either Metformin XL or placebo in a double blind, randomised fashion. Also, at this visit endothelial function tests will be performed to assess peripheral blood vessels in the forearm, central obesity will be quantified using waist circumference and waist to hip ratio (WHR) and study specific blood sampling performed (with participant consent).
At the final visit or early withdrawal the following will be performed: vital signs, safety bloods, study specific bloods (with participant consent), echocardiography, endothelial function tests and cMRI.
In the active arm, therapy will be metformin XL in an initial dose of 1000mg/day (metformin XL 500mg x2/day). Participants will continue on Metformin XL 500mg x2/day for two weeks, following safety blood checks this dose will be increased to 2000 mg/day. If the higher dose cannot be tolerated it will be reduced to 1000mg/day (or stopped if not tolerated).
The target dose of metformin XL at 2000mg/day was chosen based on a previous study of metformin in nondiabetic heart failure patients with IR, this study demonstrated a beneficial effect of metformin on insulin resistance, weight reduction and an improvement in submaximal exercise. The study used the immediate release form of metformin (target of 1000 mg x2/day) which was associated with significant gastrointestinal side effects resulting in 13% withdrawal of study medication. For this reason we have selected metformin XR due to improved gastrointestinal tolerability.
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 |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo capsules (with an identical appearance to the active drug) and containing only microcrystalline cellulose PhEur |
| Metformin XL | Active comparator | Drug: Metformin XLIn the active arm, the added therapy will be metformin XL in an initial dose of 1000mg/day (metformin XL 500mg x2/day). They will continue on Metformin XL 500mg x2/day for two weeks and after safety blood checks the metformin XL dose will be increased to 2000 mg/day. If the higher dose cannot be tolerated the dose will be reduced to 1000mg/day (and stopped if this cannot be tolerated). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Aged 18 years or over
- Participant willing and able to give informed consent.
- Documented Ischaemic Heart Disease: either angio-graphically documented coronary artery disease or a previous history of myocardial infarction/angina.
- Screening echocardiography based diagnosis of LVH (LV mass indexed to height to the allometric power of 1.7; males > 81g/h1.7, females >60g/h1.7)
- Fasting insulin resistance index ≥ 2.7 AND/OR HbA1c >5.6 and less than 6.5 at screening
Key exclusion criteria (9 listed)
- Cognitive impairment
- Type 1 or 2 Diabetes mellitus
- Chronic Heart Failure as evidenced by echocardiogram or documented diagnosis of CHF
- Left Ventricular Ejection Fraction <45% on screening echocardiography
- Contraindications to cardiac MRI (pacemakers, claustrophobia, metal implants, history of penetrative eye injury or exposure to metal fragments in eye requiring medical attention)
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 XLAlso: Diagemet XLIn the active arm, the added therapy will be metformin XL in an initial dose of 1000mg/day . They will continue on Metformin XL 500mg x2/day for 2 weeks and after safety blood checks the metformin XL dose will be increased to 2000 mg/day. If the higher dose cannot be tolerated the dose will be reduced to 1000mg/day. | Drug | Metformin XL |
| PlaceboPlacebo capsules (with an identical appearance to the active drug) containing only microcrystalline cellulose PhEur will be administered. | Drug | Placebo |
Primary outcome
Left Ventricular Mass Index
Time frame: 12 months
Cardiac magnetic resonance imaging will be performed at baseline and at 12 months, to measure Left Ventricular Mass Index in patients
9 secondary outcomes
Central and Abdominal obesity
Time frame: 12 months
Left Ventricular end systolic volume,
Time frame: 12 months
Endothelial Function
Time frame: 12 months
Insulin Resistance / Prediabetes
Time frame: 12 months
Inflammatory and other cardiovascular blood markers
Time frame: 12 months
Number of participants with Adverse Event
Time frame: 12 months
Left Ventricularend diastolic volume
Time frame: 12 months
Left Ventricular Ejection Fraction
Time frame: 12 months
Left Ventricular Mass
Time frame: 12 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 10 Apr 2019.
- Derived from this study: PubMed 25545400Mohan M, McSwiggan S, Baig F, Rutherford L, Lang CC. Metformin and its effects on myocardial dimension and left ventricular hypertrophy in normotensive patients with coronary heart disease (the MET-REMODEL study): rationale and design of the MET-REMODEL study. Cardiovasc Ther. 2015 Feb;33(1):1-8. doi: 10.1111/1755-5922.12101.
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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.
Chim Lang, MD principal investigator
University of Dundee
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin XL in people with Left Ventricular Hypertrophy and Insulin Resistance, run by University of Dundee at 1 site in United Kingdom.
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 9 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 10 Apr 2019. 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 Kingdom. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Left Ventricular Mass Index (time frame: 12 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 NCT02226510, 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 10 Apr 2019.