Metformin in Insulin Resistant Left Ventricular (LV) Dysfunction (TAYSIDE Trial) (TAYSIDE)
|Congestive Heart Failure Insulin Resistance||Drug: Metformin Drug: Matched Placebo (Capsules)||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||Metformin in Insulin Resistant LV Dysfunction, a Double-blind, Placebo-controlled Trial (TAYSIDE Trial)|
- Peak VO2 [ Time Frame: 4 months ]Peak VO2 after 4 months of intervention with either metformin or placebo. The Mean difference between baseline and after 4 months was analyzed using t-test comparing metformin and placebo.
- Possible Mechanisms That Can Explain the Improvement of Exercise Capacity [ Time Frame: 4 months ]VE/VCO2 Slope, measurement of the abnormal ventilatory response to exercise identified by an increased slope of ventilation (L/min) vs. CO2 production (VE/VCO2) (L/min) to incremental workload
|Study Start Date:||August 2007|
|Study Completion Date:||April 2009|
|Primary Completion Date:||April 2009 (Final data collection date for primary outcome measure)|
Active Comparator: 1
Receiving Metformin for 4 months
Started at 500mg bd for 2 weeks. If well tolerated, increase to 1000mg bd for 14 weeks
Placebo Comparator: 2
Matched Placebo for 4 months
Drug: Matched Placebo (Capsules)
Similar dosing regime as active comparator
Exercise incapacity is one of the major debilitating symptoms of heart failure patients. Studies showed that heart failure patients will become insulin resistance (IR) or vice versa, severity of heart failure also correlates with the severity of insulin resistance. A recent study demonstrated that if we correct diabetic patient insulin resistance by giving them a drug to make them more sensitive to the effects of insulin, their exercise capacity improves. Therefore, we think that the same effects might happen in heart failure patients who have been identified to the insulin resistance by blood test. Insulin resistance means that they have not yet become diabetic and it is a stage the diabetic patients go through before they develop diabetes.
Therefore, we plan to use a drug called metformin (a diabetic drug), give it to heart failure patients who also have IR for 4 months and examine the effects before and after 4 months of treatment. It is a double blind control study, therefore, neither the examiner nor the patient know which drug they receive (either active drug- Metformin, or a placebo).
The main objective is to assess their exercise capacity using an exercise test called Innocor System. It is a bicycle based exercise test that involves patient breathing into a mouth piece before and during exercise in order for the machine to work out the maximum oxygen consumption and pumping power of the heart.
The other objectives of the trial are looking at the possible mechanisms of improving exercise capacity. We aim to answer the following questions by doing the following tests:
Does exercise capacity improve because of
- The effect of metformin on the heart? We will answer this question by doing an ultrasound scan of the heart (Echocardiography)
- The effects on the blood vessels? We plan to perform a test called flow-mediated dilatation, it is an ultrasound scan of the artery in the arm and also assess the blood flow in the skin using a test called Laser Doppler scan (small amount of medication will be delivered through a small electric current and the blood vessels response will be assessed using the laser doppler scan)
- The effects on the muscle? We will do a muscle biopsy looking at the enzymes activities in the muscle before and after taking 4 months of medication.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00473876
|Medicine and Therapeutics, Ninewells Hospital|
|Dundee, Scotland, United Kingdom, DD1 9SY|
|Principal Investigator:||Chim Lang, MD, FRCP||University of Dundee, Scotland|