Metabolic Manipulation in Chronic Heart Failure
Primary Purpose
Chronic Heart Failure
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Perhexiline
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Heart Failure focused on measuring perhexiline, idiopathic dilated cardiomyopathy, magnetic resonance spectroscopy, cardiac energetics
Eligibility 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
Sites / Locations
- University Hospitals Brimingham NHS Foundation Trust
- University of Birmingham
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Perhexiline
Placebo
Arm Description
perhexiline 100mg bd for 1 month duration
placebo one tablet bd for 1 month duration
Outcomes
Primary Outcome Measures
Change in cardiac energetics as demonstrated by resting myocardial PCr/ATP ratio from cardiac MRS
Secondary Outcome Measures
Change in mechanical efficiency (external work / MVO2)
Change in respiratory quotient
Full Information
NCT ID
NCT00841139
First Posted
February 6, 2009
Last Updated
November 25, 2011
Sponsor
University Hospital Birmingham NHS Foundation Trust
Collaborators
British Heart Foundation
1. Study Identification
Unique Protocol Identification Number
NCT00841139
Brief Title
Metabolic Manipulation in Chronic Heart Failure
Official Title
Metabolic Manipulation in Chronic Heart Failure
Study Type
Interventional
2. Study Status
Record Verification Date
November 2011
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital Birmingham NHS Foundation Trust
Collaborators
British Heart Foundation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Heart Failure
Keywords
perhexiline, idiopathic dilated cardiomyopathy, magnetic resonance spectroscopy, cardiac energetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Perhexiline
Arm Type
Experimental
Arm Description
perhexiline 100mg bd for 1 month duration
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
placebo one tablet bd for 1 month duration
Intervention Type
Drug
Intervention Name(s)
Perhexiline
Other Intervention Name(s)
Pexsig
Intervention Description
100mg o bd
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
1 tablet bd
Primary Outcome Measure Information:
Title
Change in cardiac energetics as demonstrated by resting myocardial PCr/ATP ratio from cardiac MRS
Time Frame
1 Month
Secondary Outcome Measure Information:
Title
Change in mechanical efficiency (external work / MVO2)
Time Frame
1 Month
Title
Change in respiratory quotient
Time Frame
1 Month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael P Frenneaux, MBBS MD
Organizational Affiliation
University of Birmingham
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Roger M Beadle, MBBS
Organizational Affiliation
University of Birmingham
Official's Role
Study Director
Facility Information:
Facility Name
University Hospitals Brimingham NHS Foundation Trust
City
Birmingham
State/Province
West Midlands
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
University of Birmingham
City
Birmingham
State/Province
West Midlands
ZIP/Postal Code
B15 2TT
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
25650370
Citation
Beadle RM, Williams LK, Kuehl M, Bowater S, Abozguia K, Leyva F, Yousef Z, Wagenmakers AJ, Thies F, Horowitz J, Frenneaux MP. Improvement in cardiac energetics by perhexiline in heart failure due to dilated cardiomyopathy. JACC Heart Fail. 2015 Mar;3(3):202-11. doi: 10.1016/j.jchf.2014.09.009. Epub 2015 Jan 28.
Results Reference
derived
PubMed Identifier
21645332
Citation
Beadle RM, Williams LK, Abozguia K, Patel K, Leon FL, Yousef Z, Wagenmakers A, Frenneaux MP. Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial. Trials. 2011 Jun 6;12:140. doi: 10.1186/1745-6215-12-140.
Results Reference
derived
Learn more about this trial
Metabolic Manipulation in Chronic Heart Failure
We'll reach out to this number within 24 hrs