Metabolic Manipulation in Chronic Heart Failure

November 25, 2011 updated by: Roger Beadle, University Hospital Birmingham NHS Foundation Trust
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • West Midlands
      • Birmingham, West Midlands, United Kingdom, B15 2TH
        • University Hospitals Brimingham NHS Foundation Trust
      • Birmingham, West Midlands, United Kingdom, B15 2TT
        • University of Birmingham

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 90 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Perhexiline
perhexiline 100mg bd for 1 month duration
Drug: Perhexiline
100mg o bd
Other Names:
  • Pexsig
Placebo Comparator: Placebo
placebo one tablet bd for 1 month duration
Drug: Placebo
1 tablet bd

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in cardiac energetics as demonstrated by resting myocardial PCr/ATP ratio from cardiac MRS
Time Frame: 1 Month
1 Month

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in mechanical efficiency (external work / MVO2)
Time Frame: 1 Month
1 Month
Change in respiratory quotient
Time Frame: 1 Month
1 Month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Birmingham NHS Foundation Trust

Collaborators

British Heart Foundation

Investigators

  • Principal Investigator: Michael P Frenneaux, MBBS MD, University of Birmingham
  • Study Director: Roger M Beadle, MBBS, University of Birmingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2009

Primary Completion (Actual)

September 1, 2011

Study Completion (Actual)

September 1, 2011

Study Registration Dates

First Submitted

February 6, 2009

First Submitted That Met QC Criteria

February 10, 2009

First Posted (Estimate)

February 11, 2009

Study Record Updates

Last Update Posted (Estimate)

November 29, 2011

Last Update Submitted That Met QC Criteria

November 25, 2011

Last Verified

November 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2004-004965-14 (EudraCT Number)
  • 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)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Chronic Heart Failure

Clinical Trials on Perhexiline

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Azerbaijan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe