Perhexiline Therapy in Heart Failure With Preserved Ejection Fraction Syndrome

Overview

Up to half of all patients with clinical features of heart failure are found to have normal heart pumping function. Recently the investigators have shown that a drug called perhexiline markedly improved exercise capacity and symptoms in patients with heart failure associated with impaired cardiac pump function. In this proposal the investigators will assess whether perhexiline has beneficial effects in patients with heart failure and a normal heart pumping function.

Full Title of Study: “Randomised Double Blind Placebo Controlled Trial of Perhexiline in Heart Failure With Preserved Ejection Fraction Syndrome (HFpEF)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: February 2014

Detailed Description

Up to 50% of patients with symptoms of heart failure have a preserved left ventricular ejection fraction (HFpEF syndrome). Current therapy for systolic heart failure is targeted at inducing vasodilation and counteracting neuro-endocrine activation. There is a lack of a corresponding evidence base for the treatment of HEpEF. We have previously shown that perhexiline, an agent that increases the efficiency of energy production by shifting substrate utilization from free fatty acids towards glucose, was highly effective in improving exercise capacity, symptoms and cardiac function in patients with systolic heart failure. We have also recently shown that energy deficiency plays a major role in the pathophysiology of HFpEF. In this proposal we therefore aim to investigate the effectiveness of perhexiline in 70 HFpEF patients, in a 3 month randomised, double-blind, controlled trial. An interim analysis is planned after 20 patients.

Interventions

  • Drug: Perhexiline
    • 100mg o bd for 3 months
  • Drug: Placebo
    • Placebo one tablet bd for 3 months

Arms, Groups and Cohorts

  • Experimental: Perhexiline
    • perhexiline 100mg o bd for 3 months
  • Placebo Comparator: Placebo
    • Placebo one tablet bd for 3 months

Clinical Trial Outcome Measures

Primary Measures

  • Change in Peak oxygen consumption (Vo2max)
    • Time Frame: 3 months

Secondary Measures

  • Symptomatic Status (Modified Minnesota Living with Heart Failure Questionnaire)
    • Time Frame: 3 Months
  • Resting myocardial energetics by cardiac MR spectroscopy (MRS)
    • Time Frame: 3 months
  • Resting and exercise diastolic function (nuclear studies)
    • Time Frame: 3 months
  • Indirect measures of resting LVEDP (tissue Doppler E/Ea)
    • Time Frame: 3 months
  • Global LV Ejection Fraction (MRI / nuclear studies)
    • Time Frame: 3 months

Participating in This Clinical Trial

Inclusion Criteria

  • HFpEF will be defined as: – Clinical features consistent with heart failure – LVEF ≥ 50%, with no evidence of significant valvular disease – No hypertrophic cardiomyopathy, and no evidence of pericardial constriction – Peak VO2 < 80% predicted, with RER>1 and with a pattern of gas exchange on metabolic exercise testing indicating a cardiac cause for limitation) – Patients recruited will be in sinus rhythm Exclusion Criteria:

  • BMI >35 – Objective evidence of lung disease on formal lung function testing – Reversible myocardial ischaemia on contrast-enhanced myocardial stress Echocardiography, and no evidence of exercise-induced mitral regurgitation (>2+) – Impaired hepatic function; known hypersensitivity to perhexiline

Gender Eligibility: All

Minimum Age: 16 Years

Maximum Age: 90 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Aberdeen
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Michael P Frenneaux, MBBS MD, Principal Investigator, University of Aberdeen

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