Metabolic Manipulation in Chronic Heart Failure

Chronic Heart Failure Clinical Trial

Official title:

Metabolic Manipulation in Chronic Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00841139
• Other study ID #: 2004-004965-14
• Secondary ID: MREC: 06/Q2707/7
• Status: Completed
• Phase: Phase 2
• First received: February 6, 2009
• Last updated: November 25, 2011
• Start date: February 2009
• Est. completion date: September 2011

Study information

• Verified date: November 2011
• Source: University Hospital Birmingham NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 90 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

Drug:
• Perhexiline
100mg o bd
• Placebo
1 tablet bd

Locations

Country	Name	City	State
United Kingdom	University Hospitals Brimingham NHS Foundation Trust	Birmingham	West Midlands
United Kingdom	University of Birmingham	Birmingham	West Midlands

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Birmingham NHS Foundation Trust	British Heart Foundation

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in cardiac energetics as demonstrated by resting myocardial PCr/ATP ratio from cardiac MRS		1 Month	No
Secondary	Change in mechanical efficiency (external work / MVO2)		1 Month	No
Secondary	Change in respiratory quotient		1 Month	No