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

November 3, 2010 updated by: University Hospital Birmingham

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

44

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, W1G 8PH
        • heart Hospital, University College of London NHS
      • Oxford, United Kingdom, OX3 9DU
        • University of Oxford
    • West Midlands
      • Birmingham, West Midlands, United Kingdom, B15 2TT
        • University of Birmingham

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Peak oxygen consumption (Vo2max)
Time Frame: 3-4 months
3-4 months

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Birmingham

Collaborators

University College London Hospitals
University of Oxford
British Heart Foundation

Investigators

  • Principal Investigator: Michael Frenneaux, MD, University of Birmingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2006

Primary Completion (Actual)

August 1, 2010

Study Completion (Actual)

August 1, 2010

Study Registration Dates

First Submitted

July 10, 2007

First Submitted That Met QC Criteria

July 10, 2007

First Posted (Estimate)

July 12, 2007

Study Record Updates

Last Update Posted (Estimate)

November 4, 2010

Last Update Submitted That Met QC Criteria

November 3, 2010

Last Verified

August 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RRK 2848, 05/Q2707/325
  • PG/05/087

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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