Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy Clinical Trial

— METAL-HCM  

Official title:

Metabolic Alteration With Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy (METAL-HCM Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00500552
• Other study ID #: RRK 2848, 05/Q2707/325
• Secondary ID: PG/05/087
• Status: Completed
• Phase: Phase 2
• First received: July 10, 2007
• Last updated: November 3, 2010
• Start date: December 2006
• Est. completion date: August 2010

Study information

• Verified date: August 2010
• Source: University Hospital Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Hypertrophic Cardiomyopathy
• Hypertrophy

Intervention

Drug:
• Perhexiline/Placebo

Locations

Country	Name	City	State
United Kingdom	University of Birmingham	Birmingham	West Midlands
United Kingdom	heart Hospital, University College of London NHS	London
United Kingdom	University of Oxford	Oxford

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital Birmingham	British Heart Foundation, University College London Hospitals, University of Oxford

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak oxygen consumption (Vo2max)		3-4 months
Secondary	LV function (TDI and 2DS Echo)		3-4 months
Secondary	Symptomatic Status (questionnaire)		3-4 months
Secondary	Resting myocardial energetics (31P Cardiac MR Spectroscopy)		3-4 months
Secondary	Diastolic function at rest and during exercise (Nuclear studies)		3-4 months