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

This study has been completed.
British Heart Foundation
University College London Hospitals
University of Oxford
Information provided by:
University Hospital Birmingham Identifier:
First received: July 10, 2007
Last updated: November 3, 2010
Last verified: August 2010

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

Condition Intervention Phase
Hypertrophic Cardiomyopathy Drug: Perhexiline/Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Metabolic Alteration With Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy (METAL-HCM Study)

Resource links provided by NLM:

Further study details as provided by University Hospital Birmingham:

Primary Outcome Measures:
  • Peak oxygen consumption (Vo2max) [ Time Frame: 3-4 months ]

Secondary Outcome Measures:
  • LV function (TDI and 2DS Echo) [ Time Frame: 3-4 months ]
  • Symptomatic Status (questionnaire) [ Time Frame: 3-4 months ]
  • Resting myocardial energetics (31P Cardiac MR Spectroscopy) [ Time Frame: 3-4 months ]
  • Diastolic function at rest and during exercise (Nuclear studies) [ Time Frame: 3-4 months ]

Estimated Enrollment: 44
Study Start Date: December 2006
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Detailed Description:


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.


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.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00500552

United Kingdom
University of Birmingham
Birmingham, West Midlands, United Kingdom, B15 2TT
heart Hospital, University College of London NHS
London, United Kingdom, W1G 8PH
University of Oxford
Oxford, United Kingdom, OX3 9DU
Sponsors and Collaborators
University Hospital Birmingham
British Heart Foundation
University College London Hospitals
University of Oxford
Principal Investigator: Michael Frenneaux, MD University of Birmingham
  More Information

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00500552     History of Changes
Other Study ID Numbers: RRK 2848, 05/Q2707/325
Study First Received: July 10, 2007
Last Updated: November 3, 2010

Keywords provided by University Hospital Birmingham:
Hypertrophic Cardiomyopathy

Additional relevant MeSH terms:
Cardiomyopathy, Hypertrophic
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents processed this record on August 16, 2017