Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy
Condition: Hypertrophic Cardiomyopathy
MeSH terms: Cardiomyopathies; Cardiomyopathy, Hypertrophic; Hypertrophy
Study type: Interventional
Phase: Phase 2

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 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.
    

Intervention name(s): Perhexiline/Placebo
Intervention type(s): Drug
Intervention MeSH terms: Perhexiline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Perhexiline; Hypertrophic Cardiomyopathy