MetfoRmin and Its Effects on Left Ventricular Hypertrophy in Normotensive Patients With Coronary Artery Disease

NCT02226510 | Completed Phase 4

• 3 other identifiers: 2013CV082014-003189-2614/ES/1061
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Left Ventricular Hypertrophy; Insulin Resistance; Coronary Artery Disease; PreDiabetes

Outcome Measures

Primary Outcomes (1)

• 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

  12 months

Secondary Outcomes (9)

• Central and Abdominal obesity

  12 months

• Left Ventricular end systolic volume,

  12 months

• Endothelial Function

  12 months

• Insulin Resistance / Prediabetes

  12 months

• Inflammatory and other cardiovascular blood markers

  12 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo capsules (with an identical appearance to the active drug) and containing only microcrystalline cellulose PhEur

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).

Drug: Metformin XL

Interventions

Metformin XL DRUG

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.

Also known as: Diagemet XL

Metformin XL

Placebo DRUG

Placebo capsules (with an identical appearance to the active drug) containing only microcrystalline cellulose PhEur will be administered.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• University of Dundee: lead

Study Sites (1)

Ninewells Hospital & Medical School

Dundee, Angus, DD1 9SY, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 25545400 DERIVED

MeSH Terms

Conditions

Hypertrophy, Left Ventricular; Insulin Resistance; Coronary Artery Disease; Prediabetic State

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Coronary Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Chim Lang, MD

  University of Dundee

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2014
• First Posted: August 27, 2014
• Study Start: March 1, 2015
• Primary Completion: September 1, 2017
• Study Completion: December 1, 2017
• Last Updated: April 10, 2019

Record last verified: 2019-04

Locations

GB (1)