Metabolic Manipulation in Chronic Heart Failure

This study has been completed.
Sponsor:
Collaborator:
British Heart Foundation
Information provided by (Responsible Party):
Roger Beadle, University Hospital Birmingham NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00841139
First received: February 6, 2009
Last updated: November 25, 2011
Last verified: November 2011
  Purpose

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 Intervention Phase
Chronic 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: Metabolic Manipulation in Chronic Heart Failure

Resource links provided by NLM:


Further study details as provided by University Hospital Birmingham NHS Foundation Trust:

Primary Outcome Measures:
  • Change in cardiac energetics as demonstrated by resting myocardial PCr/ATP ratio from cardiac MRS [ Time Frame: 1 Month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in mechanical efficiency (external work / MVO2) [ Time Frame: 1 Month ] [ Designated as safety issue: No ]
  • Change in respiratory quotient [ Time Frame: 1 Month ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: February 2009
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

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

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
  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: NCT00841139

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

No publications provided by University Hospital Birmingham NHS Foundation Trust

Additional 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, R&D Birminham: RRK 2785, MHRA: 21761/0003/001, 2004-004965-14
Study First Received: February 6, 2009
Last Updated: November 25, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

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

Additional relevant MeSH terms:
Heart Failure
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 20, 2014