Metformin in Insulin Resistant Left Ventricular (LV) Dysfunction (TAYSIDE Trial) (TAYSIDE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00473876
Recruitment Status : Completed
First Posted : May 16, 2007
Results First Posted : June 6, 2013
Last Update Posted : June 6, 2013
Information provided by (Responsible Party):
Aaron K Wong, University of Dundee

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

Condition or disease Intervention/treatment Phase
Congestive Heart Failure Insulin Resistance Drug: Metformin Drug: Matched Placebo (Capsules) Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
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)
Study Start Date : August 2007
Actual Primary Completion Date : April 2009
Actual Study Completion Date : April 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: 1
Receiving Metformin for 4 months
Drug: Metformin
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

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   25 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients aged 25-80 yrs with compensated CHF in NYHA functional I-III with evidence of insulin resistance [fasting insulin resistance index values of > 2.7 are said to have insulin resistance].
  • Documented Left ventricular systolic dysfunction or LV ejection fraction < 35%

Exclusion Criteria:

  • Elderly patients (aged >80 yrs);
  • Patients with decompensated CHF (NYHA functional class IV and /or signs of decompensated CHF);
  • Renal dysfunction (serum creatinine > 160 mmol/L);
  • Patients who are unable to exercise including patients that will be excluded for reasons of safety or potential effects on exercise performance. Therefore, patients with angina or other cardiac or pulmonary symptoms potentially limiting exercise performance will be excluded.
  • Systolic blood pressure >190 mmHg at rest or >250 mmHg with exercise or diastolic blood pressure >95 mmHg at rest or >105 mmHg with exercise will also be a reason for exclusion;
  • Patients with underlying disease likely to limit life span and/or increase risk of interventions will be excluded i.e., cancer; cardiovascular disease .i.e., uncontrolled hypertension: SBP>180 mmHg or DBP, recent stroke, any severe chronic disease (including renal and hepatic disease).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00473876

United Kingdom
Medicine and Therapeutics, Ninewells Hospital
Dundee, Scotland, United Kingdom, DD1 9SY
Sponsors and Collaborators
University of Dundee
Principal Investigator: Chim Lang, MD, FRCP University of Dundee, Scotland

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Aaron K Wong, Doctor, University of Dundee Identifier: NCT00473876     History of Changes
Other Study ID Numbers: WON001
First Posted: May 16, 2007    Key Record Dates
Results First Posted: June 6, 2013
Last Update Posted: June 6, 2013
Last Verified: May 2013

Keywords provided by Aaron K Wong, University of Dundee:
Chronic Heart Failure
Insulin Resistance
Peak VO2

Additional relevant MeSH terms:
Heart Failure
Insulin Resistance
Heart Diseases
Cardiovascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Hypoglycemic Agents
Physiological Effects of Drugs