Protocol Number: 03-H-0217

Title:

Attenuating Insulin Resistance as a Therapeutic Target in the Management of Heart Failure

Number:

03-H-0217

Summary:

This study will evaluate the safety and effectiveness of the drug rosiglitazone for improving heart function in patients with heart failure and glucose intolerance or type II (adult-onset) diabetes, or both. Because of a lowered sensitivity to the hormone insulin, patients with type II diabetes or glucose-intolerance do not regulate glucose (sugar) effectively. Rosiglitazone is used to treat type II diabetes, but it is not commonly given to patients with heart failure because it can cause leg swelling and, rarely, pulmonary edema. However, patients with heart failure who also have glucose intolerance or type II diabetes generally fare worse than those with heart failure alone, and therapies that decrease insulin resistance may be beneficial to these patients.

Patients 21 years of age and older with heart failure and type II diabetes or glucose intolerance, or both, may be eligible for this study. Patients must be stable on current therapy for heart failure and must not have any planned surgeries for coronary artery disease. Candidates will be admitted to the NIH Clinical Center for from 2 to 7 days for screening procedures, which include a medical history and physical examination, blood and urine tests, electrocardiogram (ECG), chest x-ray, magnetic resonance imaging (MRI), exercise testing, and echocardiography (ultrasound test of the heart).

Participants will be randomly assigned to receive either rosiglitazone or placebo (an identical-looking pill with no active ingredient). They will take one tablet a day for the first month, one tablet twice a day for the second month, and then two tablets twice a day from the third month to the end of the study at 6 months. During the treatment period, patients will have a history, physical examination, and blood tests every 4 weeks, exercise testing and echocardiography at 3 and 6 months, and urinalysis, electrocardiogram and MRI at 6 months. To check for fluid accumulation in the legs or lungs, patients will report their weight and symptoms every 2 weeks throughout the study. After the 6-month treatment period, patients will be put back on the diabetes medicines they were taking before the study. Their physicians will be notified of possible modifications in treatment for maintaining optimum glucose tolerance.

Six months after completing treatment (one year after beginning the study), patients will return to the Clinical Center for blood tests to measure the long-term effects of rosiglitazone and to evaluate progress. They will then be invited to return to the clinic for annual checkups, if possible, or for yearly follow-up by mail or telephone to review their health status.

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Adult normal volunteers, age matched (55-75 years of age)

Adult patients greater than 21 years of age who meet the following criteria:

-Heart Failure due to ischemic heart disease or of idiopathic etiology

-Depressed LV systolic function, EF less than or equal to 0.45 by Radionuclide Angiography (MUGA)

-New York Heart Association Functional Class II or III

-Patient stable on current heart failure therapy

-Evidence of insulin resistance or type II diabetes on insulin-sensitivity screening

-No predicted cardiac revascularization therapy requirements

EXCLUSION CRITERIA:

Pregnant or lactating

History of admission for acute heart failure exacerbation within last one month

Acute myocardial infarction within the last three months

Cardiac resynchronization pacemaker placement within the last three months

Genetic defect known to have induced heart failure

Serum creatinine greater than 2.5 mg/dL.

Liver transaminase levels greater than 2.5 x upper limit of normal

Requirement for insulin therapy to control blood glucose

Current use of thiazolidinedione for diabetic control or history of discontinuation of thiazolidinedione therapy following development of side effects

Uncontrolled blood glucose levels or the use of insulin therapy to control diabetes

Immune compromise including chronic HIV, HBV, and HCV infection

Chronic systemic inflammatory disease such as SLE, rheumatoid arthritis, collagen vascular disease

Participation in unrelated research involving investigational pharmacological agent 30 days before planned dosing

Current alcohol or drug abuse

Inability to provide informed consent

Special Instructions: Currently Not Provided

Keywords:

Ventricular Contractile Function

Diastolic Dysfunction

PPAR gamma

Gene Expression Patterns

Insulin Sensitization

Recruitment Keywords:

Glucose Intolerance

Intolerance

Conditions:

Congestive Heart Failure

Investigational Drug(s):

Avanclia (Rosiqlitazone)

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Konstam MA. Comment--Val-HeFT and angiotensin-receptor blockers in perspective: A tale of the blind man and the elephant. J Card Fail. 2002 Apr;8(2):56-8. PMID: 12016625

Cohn JN, Tognoni G; Valsartan Heart Failure Trial Investigators.

A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001 Dec 6;345(23):1667-75. Summary for patients in: J Card Fail. 2002 Apr;8(2):56-8. PMID: 11759645

Coats AJ. Angiotensin type-1 receptor blockers in heart failure.

Prog Cardiovasc Dis. 2002 Jan-Feb;44(4):231-42. Review. PMID: 12007079

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