Metabolic Manipulation in Chronic Heart Failure
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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 |
- Change in cardiac energetics as demonstrated by resting myocardial PCr/ATP ratio from cardiac MRS [ Time Frame: 1 Month ] [ Designated as safety issue: No ]
- 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 |
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| 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 | |
| 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 June 18, 2013