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Metabolic Manipulation in Chronic Heart Failure

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ClinicalTrials.gov Identifier: NCT00841139
Recruitment Status : Completed
First Posted : February 11, 2009
Last Update Posted : November 29, 2011
British Heart Foundation
Information provided by (Responsible Party):
Roger Beadle, University Hospital Birmingham NHS Foundation Trust

Brief Summary:
Conventional measures used for the treatment of chronic heart failure act predominantly by reducing the work performed by the heart. In a recent study, the investigators showed that one drug (perhexiline) substantially improved symptoms and cardiac function in heart failure. The investigators wish to confirm these findings and test whether or not this drug acts by altering the heart's energy source thus augmenting the energetic status and work efficiency of the heart.

Condition or disease Intervention/treatment Phase
Chronic Heart Failure Drug: Perhexiline Drug: Placebo Phase 2

Detailed Description:
Perhexiline maleate is an antianginal agent which increases the efficiency of energy production by shifting substrate utilisation from free fatty acids towards glucose. We showed that perhexiline therapy was highly effective in improving exercise capacity, symptoms and cardiac function in patients with systolic heart failure of both ischaemic and non ischaemic aetiology. Perhexiline acts by inhibiting both carnitine palmitoyl transferase-1 (CPT-1) and CPT-2, which are key enzymes in mitochondrial free fatty acid uptake. This leads to increased myocardial glucose substrate utilization. Further we wish to ascertain whether or not this drug improves cardiac energetics and efficiency by altering substrate utilization. In this proposal we will assess the cardiac function (by cardiac Magnetic Resonance Imaging MRI), cardiac energetic status (by cardiac Magnetic Resonance Spectroscopy MRS), cardiac efficiency (via pressure-volume loops) and substrate utilization (via left and right heart catheterization), following one month of perhexiline therapy or placebo in patients with symptomatic idiopathic dilated cardiomyopathy on optimal conventional heart failure medications. An interim analysis is planned after 20 patients.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Metabolic Manipulation in Chronic Heart Failure
Study Start Date : February 2009
Primary Completion Date : September 2011
Study Completion Date : September 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Perhexiline
perhexiline 100mg bd for 1 month duration
Drug: Perhexiline
100mg o bd
Other Name: Pexsig
Placebo Comparator: Placebo
placebo one tablet bd for 1 month duration
Drug: Placebo
1 tablet bd

Primary Outcome Measures :
  1. Change in cardiac energetics as demonstrated by resting myocardial PCr/ATP ratio from cardiac MRS [ Time Frame: 1 Month ]

Secondary Outcome Measures :
  1. Change in mechanical efficiency (external work / MVO2) [ Time Frame: 1 Month ]
  2. Change in respiratory quotient [ Time Frame: 1 Month ]

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 90 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Optimally-medicated idiopathic dilated cardiomyopathy
  • Symptomatic ( NYHA IIb-III)
  • Impaired left ventricular systolic function (EF < 40%)

Exclusion Criteria:

  • Abnormal liver function tests (defined as above twice the upper limit of normal (ULN))
  • Concomitant use of Amiodarone , Quinidine , Haloperidol or Selective serotonin (5HT) uptake inhibitors such as Fluoxetine and Paroxetine which may inhibit the CYP2D6 enzyme.
  • Pre-existing evidence of peripheral neuropathy.
  • Women of childbearing potential.
  • Patients with implantable cardiac devices (or any other contraindication to MRI).
  • Obesity ( BMI > 32)
  • Obstructive sleep apnea syndrome
  • Patients with known hypersensitivity to perhexiline
  • Patients with impaired renal function (Creatinine > 250 µmol/L)
  • Valvular heart disease defined as more than moderate valvular stenosis or regurgitation.
  • Atrial Fibrillation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00841139

United Kingdom
University Hospitals Brimingham NHS Foundation Trust
Birmingham, West Midlands, United Kingdom, B15 2TH
University of Birmingham
Birmingham, West Midlands, United Kingdom, B15 2TT
Sponsors and Collaborators
University Hospital Birmingham NHS Foundation Trust
British Heart Foundation
Principal Investigator: Michael P Frenneaux, MBBS MD University of Birmingham
Study Director: Roger M Beadle, MBBS University of Birmingham

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Roger Beadle, Research Fellow to Professor MP Frenneaux, University Hospital Birmingham NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT00841139     History of Changes
Other Study ID Numbers: 2004-004965-14
MREC: 06/Q2707/7 ( Other Identifier: Regional Ethics Committe )
R&D Birminham: RRK 2785 ( Other Identifier: Hospital R&D )
MHRA: 21761/0003/001 ( Other Identifier: MHRA )
2004-004965-14 ( EudraCT Number )
First Posted: February 11, 2009    Key Record Dates
Last Update Posted: November 29, 2011
Last Verified: November 2011

Keywords provided by Roger Beadle, University Hospital Birmingham NHS Foundation Trust:
idiopathic dilated cardiomyopathy
magnetic resonance spectroscopy
cardiac energetics

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents