Metformin in Insulin Resistant Left Ventricular (LV) Dysfunction (TAYSIDE Trial)
Condition: Congestive Heart Failure; Insulin Resistance
MeSH terms: Heart Failure; Insulin Resistance
Study type: Interventional
Phase: Phase 4

Summary: 
      Will metformin improve exercise capacity in chronic heart failure patients who has insulin
      resistance (pre-diabetic- means before they become diabetic)?
    

Detailed description: 
      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

        1. The effect of metformin on the heart? We will answer this question by doing an
           ultrasound scan of the heart (Echocardiography)

        2. 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)

        3. 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.
    

Intervention name(s): Metformin; Matched Placebo (Capsules)
Intervention type(s): Drug; Drug
Intervention description(s): Started at 500mg bd for 2 weeks. If well tolerated, increase to 1000mg bd for 14 weeks; Similar dosing regime as active comparator
Intervention MeSH terms: Metformin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Chronic Heart Failure; Insulin Resistance; Metformin; Peak VO2