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

May 28, 2013 updated by: Aaron K Wong, University of Dundee

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

62

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Scotland
      • Dundee, Scotland, United Kingdom, DD1 9SY
        • Medicine and Therapeutics, Ninewells Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
4 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Dundee

Investigators

  • Principal Investigator: Chim Lang, MD, FRCP, University of Dundee, Scotland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Primary Completion (Actual)

April 1, 2009

Study Completion (Actual)

April 1, 2009

Study Registration Dates

First Submitted

May 15, 2007

First Submitted That Met QC Criteria

May 15, 2007

First Posted (Estimate)

May 16, 2007

Study Record Updates

Last Update Posted (Estimate)

June 6, 2013

Last Update Submitted That Met QC Criteria

May 28, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WON001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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