Clinical Trial: Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Metabolic Alteration With Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy (METAL-HCM Study)
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 Summary:
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:
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Sponsor: University Hospital Birmingham
Current Primary Outcome: Peak oxygen consumption (Vo2max) [ Time Frame: 3-4 months ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- 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 ]
Original Secondary Outcome: Same as current
Information By: University Hospital Birmingham
Dates:
Date Received: July 10, 2007
Date Started: December 2006
Date Completion:
Last Updated: November 3, 2010
Last Verified: August 2010
