Perhexiline Therapy in Heart Failure With Preserved Ejection Fraction Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of Aberdeen
Sponsor:
Information provided by (Responsible Party):
University of Aberdeen
ClinicalTrials.gov Identifier:
NCT00839228
First received: February 6, 2009
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Diastolic Heart Failure
Drug: Perhexiline
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Randomised Double Blind Placebo Controlled Trial of Perhexiline in Heart Failure With Preserved Ejection Fraction Syndrome (HFpEF)

Resource links provided by NLM:


Further study details as provided by University of Aberdeen:

Primary Outcome Measures:
  • Change in Peak oxygen consumption (Vo2max) [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Symptomatic Status (Modified Minnesota Living with Heart Failure Questionnaire) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
  • Resting myocardial energetics by cardiac MR spectroscopy (MRS) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Resting and exercise diastolic function (nuclear studies) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Indirect measures of resting LVEDP (tissue Doppler E/Ea) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Global LV Ejection Fraction (MRI / nuclear studies) [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: March 2009
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Perhexiline
perhexiline 100mg o bd for 3 months
Drug: Perhexiline
100mg o bd for 3 months
Other Name: Pexsig
Placebo Comparator: Placebo
Placebo one tablet bd for 3 months
Drug: Placebo
Placebo one tablet bd for 3 months
Other Name: Starch Placebo

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.

  Eligibility

Ages Eligible for Study:   16 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00839228

Contacts
Contact: Michael P Frenneaux, MBBS MD 01214158825 m.p.frenneaux@bham.ac.uk

Locations
United Kingdom
University of Aberdeen Recruiting
Aberdeen, United Kingdom, AB25 2ZD
Principal Investigator: Michael P Frenneaux, MBBS MD         
Sub-Investigator: Satnam Singh         
Sponsors and Collaborators
University of Aberdeen
Investigators
Principal Investigator: Michael P Frenneaux, MBBS MD University of Aberdeen
  More Information

No publications provided

Responsible Party: University of Aberdeen
ClinicalTrials.gov Identifier: NCT00839228     History of Changes
Other Study ID Numbers: RRK 3147, RRK 3147, MREC 08/H1207/84, EudraCT 2006-001109-28
Study First Received: February 6, 2009
Last Updated: February 5, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Aberdeen:
diastolic dysfunction
cardiac energetics
perhexiline
magnetic resonance spectroscopy

Additional relevant MeSH terms:
Heart Failure
Heart Failure, Diastolic
Heart Diseases
Cardiovascular Diseases
Perhexiline
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on July 29, 2014