Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy

NCT ID: NCT00500552

Last Updated: 2010-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2010-08-31

Brief Summary

Hypertrophic Cardiomyopathy (HCM) is a relatively common inherited heart muscle disease. Many patients experience symptoms of breathlessness, fatigue and chest pain. These symptoms are not always controlled with current therapies.

Recently the investigators showed that a drug called Perhexiline markedly improved exercise capacity and symptoms in patients with heart failure. In this proposal the investigators wish to test whether Perhexiline improves exercise capacity and relieves symptoms in patients with HCM

Detailed Description

Background:

Hypertrophic cardiomyopathy (HCM) is a complex and relatively common genetic cardiac disease and it is the most common cause of sudden cardiac death in young people, including trained athletes. In a recent study using in vivo cardiac MR spectroscopy resting PCr/ATP ratio was diminished in patients with sarcomeric HCM, indicating reduced energy availability. Importantly patients with genotypic HCM who did not yet have hypertrophy had a similar degree of impairment of cardiac PCr/ATP ratio as do patients with marked hypertrophy, implying that the disturbance may be an early feature of the disease and is not simply due to the hypertrophy. In medically refractory patients with obstruction, surgical myectomy or alcohol septal ablation may be very effective. However in patients with non obstructive HCM with symptoms refractory to standard drug therapy, there are no therapeutic options (apart from cardiac transplant in very severe cases). Recently, our group showed that Perhexiline, an antianginal agent with an oxygen-sparing metabolic effect which increases the efficiency of energy production by shifting substrate utilisation from free fatty acids towards glucose, was highly effective in improving symptoms, exercise capacity (Vo2max) and cardiac function in patients with systolic heart failure of both ischaemic and non ischaemic aetiology.

Hypothesis:

The investigators postulate that Perhexiline will improve symptomatic status, peak oxygen consumption, resting and exercise diastolic function and that this will be associated with improvement in myocardial energetic status in highly symptomatic medically refractory patients with non obstructive HCM.

Methods and design:

The study is a multi-centre randomised double blind placebo controlled trial. 50 patients who meet the entry criteria and provide written informed consent will be recruited to the study. Patients will be recruited from cardiomyopathy clinics in London, Birmingham and Oxford.

The primary end point will be peak oxygen consumption (Vo2max). Secondary end points will be resting myocardial energetics (31P Cardiac MR Spectroscopy), resting and exercise diastolic function (Myocardial Nuclear studies), Symptomatic Status (Minnesota questionnaire)and LV function (Speckle Tracking Echo measurements).

After the investigations have been performed, subjects will be randomised to receive either 100 mg of Perhexiline a day or placebo for 3 months. Following completions of three months therapy, these investigations will be repeated.

Conditions

Hypertrophic Cardiomyopathy

Keywords

Perhexiline; Hypertrophic Cardiomyopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

Perhexiline/Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Symptomatic Hypertrophic Cardiomyopathy patients

2. Abnormal Peak VO2

3. No significant LVOT obstruction at rest (gradient < 30mmHg)

4. Sinus rhythm

Exclusion Criteria

1. Abnormal LFT.

2. Concomitant use of amiodarone

3. Pre-existing evidence of peripheral neuropathy.

4. Women of childbearing potential.

5. Patients with ICD's will be excluded from the MR part of the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

British Heart Foundation

OTHER

Sponsor Role: collaborator

University College London Hospitals

OTHER

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: collaborator

University Hospital Birmingham

OTHER

Sponsor Role: lead

Principal Investigators

Michael Frenneaux, MD

Role: PRINCIPAL_INVESTIGATOR

University of Birmingham

Locations

heart Hospital, University College of London NHS

London, London, United Kingdom

University of Birmingham

Birmingham, West Midlands, United Kingdom

University of Oxford

Oxford, , United Kingdom

Countries

United Kingdom

References

Abozguia K, Elliott P, McKenna W, Phan TT, Nallur-Shivu G, Ahmed I, Maher AR, Kaur K, Taylor J, Henning A, Ashrafian H, Watkins H, Frenneaux M. Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy. Circulation. 2010 Oct 19;122(16):1562-9. doi: 10.1161/CIRCULATIONAHA.109.934059. Epub 2010 Oct 4.

Reference Type: DERIVED

PMID: 20921440 (View on PubMed)

Other Identifiers

PG/05/087

Identifier Type: -

Identifier Source: secondary_id

RRK 2848, 05/Q2707/325

Identifier Type: -

Identifier Source: org_study_id