Metabolic Syndrome XPhase 2MET-DIMENCT02017561
Metformin in the Diastolic Dysfunction of Metabolic Syndrome
A Phase 2 study testing Lifestyle Counseling and Metformin in people with Metabolic Syndrome X and Diastolic Dysfunction, run by Universidade do Porto at 1 site in Portugal.
Trial summary
Metabolic syndrome (MS) is a cluster of risk factors for cardiovascular disease with increasing prevalence worldwide and insulin resistance is central to its pathophysiology and multi-organ deleterious effects. Read more about this study
- Who is it for?
- Ages 40 to 64 years
- Conditions the study is for
- Metabolic Syndrome X, Diastolic Dysfunction, Insulin Resistance
- What is being tested?
- Lifestyle Counseling and Metformin
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 sitePortugal
- Study dates
- Jan 2014to Dec 2019
- 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 40 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Non-diabetic adults aged between 40 and 64 years fulfilling the American Heart Association/National Heart, Lung and Blood Institute diagnostic criteria of metabolic syndrome (at least 3 of the following: waist circumference ≥102 cm (males) or ≥88 cm (females); fasting triglycerides≥150 mg/dL or on drug therapy for decreasing triglycerides; fasting HDL-cholesterol ˂40 mg/dL (males) or ˂50 mg/dL (females) or on drug therapy for increase HDL-c; systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg or on antihypertensive drug therapy; fasting glycemia≥100 mg/dL
- Echocardiographic evidence of left ventricle diastolic dysfunction at rest (mean E'˂10,2 cm/s if 40-59 years and ˂7,2 cm/s if 60-64 years).
Who cannot join
- diagnosis of diabetes mellitus according to the American Diabetes Association criteria;
- previous diagnosis of ischemic heart disease;
- moderate or severe cardiac valvular disease;
- left ventricle ejection fraction lower than 50%
- pericardial disease;
- uncontrolled atrial or ventricular tachyarrhythmias;
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- chronic kidney disease (estimated creatinine clearance lower than 60 mL/min);
- significant liver disease (aspartate aminotransferase or alanine aminotransferase equal or above 2.5 times the upper limit of normal);
- females who are pregnant, planning to become pregnant or who admit sexual activity without appropriate contraception;
- lactation;
- unable to perform cardiopulmonary exercise test;
- recent (less than 1 month) change in drug therapy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Metformin in the Diastolic Dysfunction of Metabolic Syndrome: MET-DIME Trial
Metabolic syndrome (MS) is a cluster of risk factors for cardiovascular disease with increasing prevalence worldwide and insulin resistance is central to its pathophysiology and multi-organ deleterious effects. One of the most affected organs, the heart, undergoes a remodeling process with an increase in fibrous tissue that impairs global cardiac function. Considering that myocardial fibrosis increases myocardial stiffness, one important determinant of diastolic function, it probably contributes decisively to subclinical left ventricular diastolic dysfunction (DD) and heart failure with preserved ejection fraction in patients with MS.
Since insulin resistance is a dominant player in the pathophysiology of MS, improvement of the metabolic profile of these patients with metformin might be associated with favorable remodeling of myocardial structure and an improvement in myocardial function. Metformin is a widely used drug to treat type 2 diabetes mellitus and is considered an option in the treatment of high-risk non-diabetic patients with MS, in addition to lifestyle counseling including a healthy diet and physical activity.
Read more
In this way, we aim to: i) assess if treating non-diabetic patients with MS and DD with metformin in addition to lifestyle counseling decreases cardiac fibrosis and improves diastolic function and assess its impact in functional capacity and health-related quality of life (HRQoL); ii) evaluate if biomarkers of cardiac remodeling and inflammation are predictive factors of response to metformin treatment in these patients.
This is a prospective, randomized, open-label, blinded-endpoint (PROBE) trial (scheduled follow-up of 24 months) with 2 arms: lifestyle counseling only and lifestyle counseling plus metformin (maximum dose of 1000mg twice daily).
The primary endpoint will be change in change in mean of septal and lateral early diastolic mitral annular velocities (E') (at the end of the 24 months of follow-up).
The secondary endpoints will include a composite of major cardiovascular events; diastolic function parameters at rest; plasma levels of insulin, glucose, insulin resistance index, NTproBNP, high-sensitivity C-reactive protein, tumor necrosis factor-α (TNFα), tissue inhibitor of matrix metalloproteinase type 1 (TIMP1) and growth differentiation factor-15 (GDF-15); functional capacity; epicardial, pericardial and abdominal adipose tissue volumes, and coronary calcium score; HRQoL.
- Being tested
- Lifestyle Counseling, Metformin
- Keywords
- Diastolic dysfunction, Metabolic syndrome, Metformin
- Medical subject headings
- Metabolic Syndrome, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lifestyle CounselingBehavioural
Written and individualized information during the interview in all clinic visits, emphasizing the importance of a healthy lifestyle, engaging on regular moderate-intensity physical activity and eating an healthy diet.
MetforminDrug
Also called Risidon, Glucophage
Metformin treatment titrated to a maximum dose of 1000mg twice a day. Metformin treatment will start with 500mg at breakfast during the first week and, if well tolerated, increased to 500mg twice a day (breakfast and dinner) in the second week, 1000mg at breakfast and 500mg at dinner in the third week and finally for the target dose of 1000mg twice a day.
| Study group | Role | What they receive |
|---|---|---|
| Lifestyle Counseling | Active comparator | Written and individualized information during the interview in all clinic visits, emphasizing the importance of regular moderate-intensity physical activity and healthy diet. Receives: Behavioral: Lifestyle Counseling |
| Metformin + Lifestyle Counseling | Experimental | Metformin: maximum dose of 1000mg twice daily. Lifestyle counseling: Written and individualized information during the interview in all clinic visits, emphasizing the importance of regular moderate-intensity physical activity and healthy diet. Receives: Behavioral: Lifestyle Counseling; Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mean early diastolic mitral annular velocity (cm/s)
Change in mean of septal and lateral early diastolic mitral annular velocities (E'), assessed by tissue doppler echocardiography
Measured: Baseline, 6,12 and 24 months
Secondary outcomes (7)
Major adverse cardiovascular events
Composite outcome of major cardiovascular events: nonfatal myocardial infarction, nonfatal stroke, death judged to be due to cardiovascular causes, hospitalization for heart failure, angina confirmed by ischemic changes on exercise tolerance testing or by clinically significant obstruction on coronary angiography or need for revascularization with angioplasty or coronary-artery bypass grafting.
Measured: 12 and 24 months
Diastolic echocardiographic parameters
E/E´ ratio, isovolumetric relaxation time (IVRT), E/A ratio, mitral deceleration time, grade of diastolic dysfunction according to the consensus document of the American Society of Echocardiography and European Society of Echocardiography, strain rate during isovolumetric relaxation (SR-IVR) and E/SR-IVR ratio.
Measured: Baseline, 6, 12, 24 months
Plasma levels of inflammatory and metabolic biomarkers
Plasma levels of insulin, glucose, insulin resistance index, NTproBNP, high-sensitivity C-reactive protein, TNFα, TIMP1 e GDF-15 (growth differentiation factor 15).
Measured: Baseline, 6, 12, 24 months
Functional capacity during cardiopulmonary exercise test
Functional capacity during cardiopulmonary exercise test: all patients will perform a symptom-limited treadmill exercise testing according to modified Bruce protocol, with simultaneous respiratory gas analysis. Peak oxygen uptake, anaerobic threshold and ventilatory efficiency will be determined.
Measured: Baseline, 12, 24 months
Epicardial, pericardial and abdominal adipose tissue volumes
Cardiac multidetector CT without contrast administration to measure epicardial, pericardial and abdominal adipose tissue volumes
Measured: Baseline, 24 months
Coronary artery calcium quantification
Cardiac multidetector CT without contrast administration to assess coronary artery calcification (calcium score)
Measured: Baseline, 24 months
Healthcare related quality of life
The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) will be used to assess general health status and HRQoL.
Measured: Baseline, 12, 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2013 (estimated)
- Study startJan 2014
- Primary completionDec 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic Syndrome XStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universidade do Porto
- Sponsor type
- University, hospital or other
- Collaborators
- Centro Hospitalar de Vila Nova de Gaia/Espinho, Merck Serono International SA
- Responsible party
- Principal investigator, Ricardo Ladeiras-Lopes, Universidade do Porto
- Investigators
- Ricardo Ladeiras-Lopes, MD, Principal investigator, Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of the University of PortoAdelino F Leite-Moreira, MD,PhD,FETCS, Study chair, Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of the University of PortoVasco Gama, MD, Study chair, Department of Cardiology, Gaia/Espinho Hospital Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02017561
- Sponsor's protocol ID
- 01.00240
- Acronym
- MET-DIME
- Status last verified
- Mar 2020
- First submitted
- 16 Dec 2013
- Last updated
- 25 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin in the Diastolic Dysfunction of Metabolic Syndrome: MET-DIME Trial
- ClinicalTrials.gov ID
- NCT02017561
- Acronym / sponsor ID
- MET-DIME / 01.00240
- Keywords
- Diastolic dysfunction, Metabolic syndrome, Metformin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Universidade do PortoUniversity, hospital or other
- Collaborators
- Centro Hospitalar de Vila Nova de Gaia/Espinho, Merck Serono International SA
- Study start
- Jan 2014
- Primary completion
- Dec 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 20 Dec 2013 (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.
Metabolic syndrome (MS) is a cluster of risk factors for cardiovascular disease with increasing prevalence worldwide and insulin resistance is central to its pathophysiology and multi-organ deleterious effects. One of the most affected organs, the heart, undergoes a remodeling process with an increase in fibrous tissue that impairs global cardiac function. Considering that myocardial fibrosis increases myocardial stiffness, one important determinant of diastolic function, it probably contributes decisively to subclinical left ventricular diastolic dysfunction (DD) and heart failure with preserved ejection fraction in patients with MS.
Since insulin resistance is a dominant player in the pathophysiology of MS, improvement of the metabolic profile of these patients with metformin might be associated with favorable remodeling of myocardial structure and an improvement in myocardial function. Metformin is a widely used drug to treat type 2 diabetes mellitus and is considered an option in the treatment of high-risk non-diabetic patients with MS, in addition to lifestyle counseling including a healthy diet and physical activity.
In this way, we aim to: i) assess if treating non-diabetic patients with MS and DD with metformin in addition to lifestyle counseling decreases cardiac fibrosis and improves diastolic function and assess its impact in functional capacity and health-related quality of life (HRQoL); ii) evaluate if biomarkers of cardiac remodeling and inflammation are predictive factors of response to metformin treatment in these patients.
This is a prospective, randomized, open-label, blinded-endpoint (PROBE) trial (scheduled follow-up of 24 months) with 2 arms: lifestyle counseling only and lifestyle counseling plus metformin (maximum dose of 1000mg twice daily).
The primary endpoint will be change in change in mean of septal and lateral early diastolic mitral annular velocities (E') (at the end of the 24 months of follow-up).
The secondary endpoints will include a composite of major cardiovascular events; diastolic function parameters at rest; plasma levels of insulin, glucose, insulin resistance index, NTproBNP, high-sensitivity C-reactive protein, tumor necrosis factor-α (TNFα), tissue inhibitor of matrix metalloproteinase type 1 (TIMP1) and growth differentiation factor-15 (GDF-15); functional capacity; epicardial, pericardial and abdominal adipose tissue volumes, and coronary calcium score; HRQoL.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lifestyle Counseling | Active comparator | Behavioral: Lifestyle CounselingWritten and individualized information during the interview in all clinic visits, emphasizing the importance of regular moderate-intensity physical activity and healthy diet. |
| Metformin + Lifestyle Counseling | Experimental | Behavioral: Lifestyle Counseling, Drug: MetforminMetformin: maximum dose of 1000mg twice daily. Lifestyle counseling: Written and individualized information during the interview in all clinic visits, emphasizing the importance of regular moderate-intensity physical activity and healthy diet. |
Who may qualify
- Ages
- 40 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Non-diabetic adults aged between 40 and 64 years fulfilling the American Heart Association/National Heart, Lung and Blood Institute diagnostic criteria of metabolic syndrome (at least 3 of the following: waist circumference ≥102 cm (males) or ≥88 cm (females); fasting triglycerides≥150 mg/dL or on drug therapy for decreasing triglycerides; fasting HDL-cholesterol ˂40 mg/dL (males) or ˂50 mg/dL (females) or on drug therapy for increase HDL-c; systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg or on antihypertensive drug therapy; fasting glycemia≥100 mg/dL
- Echocardiographic evidence of left ventricle diastolic dysfunction at rest (mean E'˂10,2 cm/s if 40-59 years and ˂7,2 cm/s if 60-64 years).
Key exclusion criteria (12 listed)
- diagnosis of diabetes mellitus according to the American Diabetes Association criteria;
- previous diagnosis of ischemic heart disease;
- moderate or severe cardiac valvular disease;
- left ventricle ejection fraction lower than 50%
- pericardial 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 |
|---|---|---|
| Lifestyle CounselingWritten and individualized information during the interview in all clinic visits, emphasizing the importance of a healthy lifestyle, engaging on regular moderate-intensity physical activity and eating an healthy diet. | Behavioural | Lifestyle Counseling, Metformin + Lifestyle Counseling |
| MetforminAlso: Risidon, GlucophageMetformin treatment titrated to a maximum dose of 1000mg twice a day. Metformin treatment will start with 500mg at breakfast during the first week and, if well tolerated, increased to 500mg twice a day (breakfast and dinner) in the second week, 1000mg at breakfast and 500mg at dinner in the third week and finally for the target dose of 1000mg twice a day. | Drug | Metformin + Lifestyle Counseling |
Primary outcome
Change in mean early diastolic mitral annular velocity (cm/s)
Time frame: Baseline, 6,12 and 24 months
Change in mean of septal and lateral early diastolic mitral annular velocities (E'), assessed by tissue doppler echocardiography
7 secondary outcomes
Major adverse cardiovascular events
Time frame: 12 and 24 months
Diastolic echocardiographic parameters
Time frame: Baseline, 6, 12, 24 months
Plasma levels of inflammatory and metabolic biomarkers
Time frame: Baseline, 6, 12, 24 months
Functional capacity during cardiopulmonary exercise test
Time frame: Baseline, 12, 24 months
Epicardial, pericardial and abdominal adipose tissue volumes
Time frame: Baseline, 24 months
Coronary artery calcium quantification
Time frame: Baseline, 24 months
Healthcare related quality of life
Time frame: Baseline, 12, 24 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 25 Mar 2020.
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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.
Ricardo Ladeiras-Lopes, MD principal investigator
Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of the University of Porto
Adelino F Leite-Moreira, MD,PhD,FETCS study chair
Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine of the University of Porto
Vasco Gama, MD study chair
Department of Cardiology, Gaia/Espinho Hospital Centre
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 Lifestyle Counseling and Metformin in people with Metabolic Syndrome X and Diastolic Dysfunction, run by Universidade do Porto at 1 site in Portugal.
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 2 inclusion and 12 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 25 Mar 2020. 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 Portugal. 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. 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?
Change in mean early diastolic mitral annular velocity (cm/s) (time frame: Baseline, 6,12 and 24 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 25 Mar 2020.