title: Metabolic manipulation in chronic heart failure: study protocol for a randomised controlled trial.
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 β-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.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00841139 ISRCTN: ISRCTN72887836.
authors.affiliation: University of Aberdeen, School of Medicine and Dentistry, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD, UK. r01rmb0@abdn.ac.uk
authors.forename: Roger M
authors.initials: RM
authors.lastname: Beadle
authors.forename: Lynne K
authors.initials: LK
authors.lastname: Williams
authors.forename: Khaild
authors.initials: K
authors.lastname: Abozguia
authors.forename: Kiran
authors.initials: K
authors.lastname: Patel
authors.forename: Francisco Leyva
authors.initials: FL
authors.lastname: Leon
authors.forename: Zaheer
authors.initials: Z
authors.lastname: Yousef
authors.forename: Anton
authors.initials: A
authors.lastname: Wagenmakers
authors.forename: Michael P
authors.initials: MP
authors.lastname: Frenneaux
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D006328:Cardiac Catheterization; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000097:blood / Q000627:therapeutic use*; D004311:Double-Blind Method; D016903:Drug Monitoring; D015150:Echocardiography, Doppler; D004734:Energy Metabolism / Q000187:drug effects*; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D009206:Myocardium / Q000378:metabolism*; D010480:Perhexiline / Q000097:blood / Q000627:therapeutic use*; D010725:Phosphocreatine / Q000378:metabolism; D015990:Placebo Effect; D011446:Prospective Studies; D020127:Recovery of Function; D012107:Research Design; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D002317:Cardiovascular Agents; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D010480:Perhexiline