Cyclosporine A to Treat Hypertrophic Cardiomyopathy (HCM)

NCT00001965 | Completed Phase 2

• 2 other identifiers: 00003400-H-0034
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the effectiveness of the drug cyclosporine in treating hypertrophic cardiomyopathy (HCM), a condition in which the heart muscle thickens. The thickened muscle can impair the heart's pumping action or decrease its blood supply, or both. Various symptoms, such as chest pain, shortness of breath, fatigue, and palpitations, may result. In animal studies, cyclosporine prevented heart muscle from thickening in mice that had been engineered to develop thick hearts. Patients with HCM 18 to 75 years old are screened for this study under protocol 98-H-0102 and this protocol. Screening tests include blood tests, echocardiogram to measure heart thickness, Holter monitor to record heartbeats, treadmill exercise test, and various imaging tests including a thallium scan, radionuclide angiography, magnetic resonance imaging (MRI), and cardiac catheterization to examine heart function and blood supply. Patients admitted to the study will be randomly assigned to take either cyclosporine tablets or a placebo (a look-alike tablet with no active ingredient) twice a day for 6 months. During a brief hospital stay at the start of the study, blood samples will be taken to measure cyclosporine levels. After discharge, heart rate and blood pressure will be checked and blood tests done during follow-up visits once a week for 2 weeks and then every two weeks until the end of the 6-month treatment period. At that time, patients will be hospitalized a second time for repeat tests to determine the effects of the drug on the heart condition. They include thallium scan, radionuclide angiogram, MRI, treadmill exercise test, cardiac catheterization, and echocardiogram. An echocardiogram and MRI will be repeated 1 year after the start of the study to evaluate long term effects of the drug, if any.

Conditions

Cardiomyopathy, Hypertrophic; Heart Hypertrophy

Keywords

Calcineurin; Cardiac Hypertrophy; Hypertrophic Cardiomyopathy

Interventions

Cyclosporine A DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

Patients of either gender, aged 18-75 years, with HCM caused by sarcomeric gene mutations determined by existing protocols. LV wall thickness of greater than or equal to 20 mm measured in any LV segment by MRI. Severe symptoms refractory to medical treatment (New York Heart Association functional class III or IV). No LV outflow tract obstruction at rest greater than 30 mm Hg as determined by cardiac catheterization. No coronary artery disease (greater than 50% arterial luminal narrowing of a major epicardial vessel). No chronic atrial fibrillation. No bleeding disorder (PTT greater than 35 sec, pro time greater than 14 sec, platelet count less than 154 k/mm(3). No anemia (Hb less than 12.7 g/dl in males and less than 11.0 g/dl in females). No renal impairment (serum creatinine greater than 1.3 mg/dl). No hepatitis B or C; nor unexplained abnormal LFTs. No inability to estimate LV wall thickness. No positive urine pregnancy test. No pregnant or lactating female patients. No concurrent use of immunosuppressives or steroids. No diabetes mellitus. No history of malignancy other than skin tumors (squamous and basal cell) in the last 5 years. No condition that excludes the patient from undergoing an MRI test.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Heart, Lung and Blood Institute (NHLBI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Spirito P, Maron BJ. Relation between extent of left ventricular hypertrophy and occurrence of sudden cardiac death in hypertrophic cardiomyopathy. J Am Coll Cardiol. 1990 Jun;15(7):1521-6. doi: 10.1016/0735-1097(90)92820-r.

  PMID: 2140576 BACKGROUND

• Molkentin JD, Lu JR, Antos CL, Markham B, Richardson J, Robbins J, Grant SR, Olson EN. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell. 1998 Apr 17;93(2):215-28. doi: 10.1016/s0092-8674(00)81573-1.

  PMID: 9568714 BACKGROUND

• Sussman MA, Lim HW, Gude N, Taigen T, Olson EN, Robbins J, Colbert MC, Gualberto A, Wieczorek DF, Molkentin JD. Prevention of cardiac hypertrophy in mice by calcineurin inhibition. Science. 1998 Sep 11;281(5383):1690-3. doi: 10.1126/science.281.5383.1690.

  PMID: 9733519 BACKGROUND

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic; Cardiomegaly

Interventions

Cyclosporine

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: January 18, 2000
• First Posted: December 10, 2002
• Study Start: December 1, 1999
• Study Completion: February 1, 2001
• Last Updated: March 4, 2008

Record last verified: 1999-11

Locations

US (1)