Metabolic manipulation in chronic heart failure

study protocol for a randomised controlled trial

Roger M Beadle, Lynne K Williams, Khaild Abozguia, Kiran Patel, Francisco Leyva Leon, Zaheer Yousef, Anton Wagenmakers, Michael P Frenneaux

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

BACKGROUND: Heart failure is a major cause of morbidity and mortality in society. Current medical therapy centres on neurohormonal modulation with angiotensin converting enzyme inhibitors and ß-blockers. There is growing evidence for the use of metabolic manipulating agents as adjunctive therapy in patients with heart failure. We aim to determine the effect of perhexiline on cardiac energetics and alterations in substrate utilisation in patients with non-ischaemic dilated cardiomyopathy. METHODS: A multi-centre, prospective, randomised double-blind, placebo-controlled trial of 50 subjects with non-ischaemic dilated cardiomyopathy recruited from University Hospital Birmingham NHS Foundation Trust and Cardiff and Vale NHS Trust. Baseline investigations include magnetic resonance spectroscopy to assess cardiac energetic status, echocardiography to assess left ventricular function and assessment of symptomatic status. Subjects are then randomised to receive 200 mg perhexiline maleate or placebo daily for 4 weeks with serum drug level monitoring. All baseline investigations will be repeated at the end of the treatment period. A subgroup of patients will undergo invasive investigations with right and left heart catheterisation to calculate respiratory quotient, and mechanical efficiency. The primary endpoint is an improvement in the phosphocreatine to adenosine triphosphate ratio at 4 weeks. Secondary end points are: i) respiratory quotient; ii) mechanical efficiency; iii) change in left ventricular (LV) function. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00841139 ISRCTN: ISRCTN2887836.
Original languageEnglish
Article number140
Number of pages1
JournalTrials
Volume12
DOIs
Publication statusPublished - 6 Jun 2011

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Randomized Controlled Trials
Heart Failure
Dilated Cardiomyopathy
Left Ventricular Function
Perhexiline
Placebos
Phosphocreatine
Drug Monitoring
Cardiac Catheterization
Angiotensin-Converting Enzyme Inhibitors
Echocardiography
Magnetic Resonance Spectroscopy
Therapeutics
Adenosine Triphosphate
Morbidity
Mortality
Serum
perhexiline maleate

Keywords

  • adenosine triphosphate
  • cardiomyopathy, dilated
  • cardiovascular agents
  • double-blind method
  • drug monitoring
  • echocardiography, Doppler
  • energy metabolism
  • Great Britain
  • heart catheterization
  • heart failure
  • humans
  • magnetic resonance imaging
  • magnetic resonance spectroscopy
  • myocardium
  • perhexiline
  • phosphocreatine
  • placebo effect
  • prospective studies
  • recovery of function
  • research design
  • stroke volume
  • time factors
  • treatment outcome
  • ventricular function, left

Cite this

Beadle, R. M., Williams, L. K., Abozguia, K., Patel, K., Leon, F. L., Yousef, Z., ... Frenneaux, M. P. (2011). Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial. Trials, 12, [140]. https://doi.org/10.1186/1745-6215-12-140

Metabolic manipulation in chronic heart failure : study protocol for a randomised controlled trial. / Beadle, Roger M; Williams, Lynne K; Abozguia, Khaild; Patel, Kiran; Leon, Francisco Leyva; Yousef, Zaheer; Wagenmakers, Anton; Frenneaux, Michael P.

In: Trials, Vol. 12, 140, 06.06.2011.

Research output: Contribution to journalArticle

Beadle, RM, Williams, LK, Abozguia, K, Patel, K, Leon, FL, Yousef, Z, Wagenmakers, A & Frenneaux, MP 2011, 'Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial', Trials, vol. 12, 140. https://doi.org/10.1186/1745-6215-12-140
Beadle, Roger M ; Williams, Lynne K ; Abozguia, Khaild ; Patel, Kiran ; Leon, Francisco Leyva ; Yousef, Zaheer ; Wagenmakers, Anton ; Frenneaux, Michael P. / Metabolic manipulation in chronic heart failure : study protocol for a randomised controlled trial. In: Trials. 2011 ; Vol. 12.
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AU - Leon, Francisco Leyva

AU - Yousef, Zaheer

AU - Wagenmakers, Anton

AU - Frenneaux, Michael P

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N2 - BACKGROUND: Heart failure is a major cause of morbidity and mortality in society. Current medical therapy centres on neurohormonal modulation with angiotensin converting enzyme inhibitors and ß-blockers. There is growing evidence for the use of metabolic manipulating agents as adjunctive therapy in patients with heart failure. We aim to determine the effect of perhexiline on cardiac energetics and alterations in substrate utilisation in patients with non-ischaemic dilated cardiomyopathy. METHODS: A multi-centre, prospective, randomised double-blind, placebo-controlled trial of 50 subjects with non-ischaemic dilated cardiomyopathy recruited from University Hospital Birmingham NHS Foundation Trust and Cardiff and Vale NHS Trust. Baseline investigations include magnetic resonance spectroscopy to assess cardiac energetic status, echocardiography to assess left ventricular function and assessment of symptomatic status. Subjects are then randomised to receive 200 mg perhexiline maleate or placebo daily for 4 weeks with serum drug level monitoring. All baseline investigations will be repeated at the end of the treatment period. A subgroup of patients will undergo invasive investigations with right and left heart catheterisation to calculate respiratory quotient, and mechanical efficiency. The primary endpoint is an improvement in the phosphocreatine to adenosine triphosphate ratio at 4 weeks. Secondary end points are: i) respiratory quotient; ii) mechanical efficiency; iii) change in left ventricular (LV) function. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00841139 ISRCTN: ISRCTN2887836.

AB - BACKGROUND: Heart failure is a major cause of morbidity and mortality in society. Current medical therapy centres on neurohormonal modulation with angiotensin converting enzyme inhibitors and ß-blockers. There is growing evidence for the use of metabolic manipulating agents as adjunctive therapy in patients with heart failure. We aim to determine the effect of perhexiline on cardiac energetics and alterations in substrate utilisation in patients with non-ischaemic dilated cardiomyopathy. METHODS: A multi-centre, prospective, randomised double-blind, placebo-controlled trial of 50 subjects with non-ischaemic dilated cardiomyopathy recruited from University Hospital Birmingham NHS Foundation Trust and Cardiff and Vale NHS Trust. Baseline investigations include magnetic resonance spectroscopy to assess cardiac energetic status, echocardiography to assess left ventricular function and assessment of symptomatic status. Subjects are then randomised to receive 200 mg perhexiline maleate or placebo daily for 4 weeks with serum drug level monitoring. All baseline investigations will be repeated at the end of the treatment period. A subgroup of patients will undergo invasive investigations with right and left heart catheterisation to calculate respiratory quotient, and mechanical efficiency. The primary endpoint is an improvement in the phosphocreatine to adenosine triphosphate ratio at 4 weeks. Secondary end points are: i) respiratory quotient; ii) mechanical efficiency; iii) change in left ventricular (LV) function. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00841139 ISRCTN: ISRCTN2887836.

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