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

Insulin Resistance Clinical Trial

— TAYSIDE  

Official title:

Metformin in Insulin Resistant LV Dysfunction, a Double-blind, Placebo-controlled Trial (TAYSIDE Trial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00473876
• Other study ID #: WON001
• Status: Completed
• Phase: Phase 4
• First received: May 15, 2007
• Last updated: May 28, 2013
• Start date: August 2007
• Est. completion date: April 2009

Study information

• Verified date: May 2013
• Source: University of Dundee
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 25 Years to 80 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Congestive Heart Failure
• Heart Failure
• Insulin Resistance

Intervention

Drug:
• Metformin
Started at 500mg bd for 2 weeks. If well tolerated, increase to 1000mg bd for 14 weeks
• Matched Placebo (Capsules)
Similar dosing regime as active comparator

Locations

Country	Name	City	State
United Kingdom	Medicine and Therapeutics, Ninewells Hospital	Dundee	Scotland

Sponsors (1)

Lead Sponsor	Collaborator
University of Dundee

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak VO2	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.	4 months	No
Secondary	Possible Mechanisms That Can Explain the Improvement of Exercise Capacity	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	4 months	No