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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00500552
Recruitment Status : Completed
First Posted : July 12, 2007
Last Update Posted : November 4, 2010
British Heart Foundation
University College London Hospitals
University of Oxford
Information provided by:
University Hospital Birmingham

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

Condition or disease Intervention/treatment Phase
Hypertrophic Cardiomyopathy Drug: Perhexiline/Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: Metabolic Alteration With Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy (METAL-HCM Study)
Study Start Date : December 2006
Actual Primary Completion Date : August 2010
Actual Study Completion Date : August 2010

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

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00500552

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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
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Principal Investigator: Michael Frenneaux, MD University of Birmingham
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00500552    
Other Study ID Numbers: RRK 2848, 05/Q2707/325
First Posted: July 12, 2007    Key Record Dates
Last Update Posted: November 4, 2010
Last Verified: August 2010
Keywords provided by University Hospital Birmingham:
Hypertrophic Cardiomyopathy
Additional relevant MeSH terms:
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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
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents