title: Effect of L-type calcium channel blocker (amlodipine) on myocardial iron deposition in patients with thalassaemia with moderate-to-severe myocardial iron deposition: protocol for a randomised, controlled trial.
abstract: BACKGROUND
  Sideroblastic cardiomyopathy secondary to repeated blood transfusions is a feared complication in thalassaemia. Control of myocardial iron is thus becoming the cornerstone of thalassaemia management. Recent evidence suggests a role for L-type Ca(2+) channels in mediating iron uptake by the heart. Blocking the cellular iron uptake through these channels may add to the benefit of therapy to standard chelation in reducing myocardial iron. We aim to determine the efficacy of amlodipine (a calcium channel blocker) as an adjunct to standard aggressive chelation in retarding myocardial iron deposition in thalassaemics with or without cardiomyopathy.
  
  
  RESULTS
  The primary outcome is to compare the efficacy of amlodipine+chelation (intervention) versus standard chelation (control) in retarding myocardial iron deposition. Secondary outcomes include the effect of amlodipine therapy on systolic and diastolic function, strain and strain rate and liver iron content.
  
  
  METHODS
  This is a single-centre, parallel-group, prospective randomised control trial. Twenty patients will be randomised in a 1:1 allocation ratio into the intervention and control arms. In addition to conventional echocardiography, MRI T2* values for assessment of cardiac and liver iron load will be obtained at baseline and at 6 and 12 months. Cardiac T2* will be reported as the geometric mean and per cent coefficient of variation, and an increase in cardiac T2* values from baseline will be used as an end point to compare the efficacy of therapy. A p Value of <0.05 will be considered significant.
  
  
  METHODS
  Department of Pediatric and Child Health, Aga Khan University Hospital, Karachi, Pakistan.
  
  
  BACKGROUND
  This study has been approved by the Ethics Review Committee and Clinical Trials Unit at The Aga Khan University with respect to scientific content and compliance with applicable research and human subjects regulations. Findings will be reported through scientific publications and research conferences and project summary papers for participants.
  
  
  BACKGROUND
  ClinicalTrials.Gov. Registration no: NCT02065492.
authors.affiliation: Department of Pediatrics and Child Health, Aga Khan University, Karachi, Sindh, Pakistan.
authors.forename: Amarah
authors.identifier: http://orcid.org/0000-0002-1860-0552
authors.initials: A
authors.lastname: Shakoor
authors.affiliation: Department of Pediatrics and Child Health, Aga Khan University, Karachi, Sindh, Pakistan.
authors.forename: Maaman
authors.initials: M
authors.lastname: Zahoor
authors.affiliation: Department of Pediatrics and Child Health, Aga Khan University, Karachi, Sindh, Pakistan.
authors.forename: Alina
authors.initials: A
authors.lastname: Sadaf
authors.affiliation: Department of Pediatrics and Child Health, Aga Khan University, Karachi, Sindh, Pakistan.
authors.forename: Najveen
authors.initials: N
authors.lastname: Alvi
authors.affiliation: Department of Pediatrics and Child Health, Aga Khan University, Karachi, Sindh, Pakistan.
authors.forename: Zehra
authors.initials: Z
authors.lastname: Fadoo
authors.affiliation: Department of Pediatrics and Child Health, Aga Khan University, Karachi, Sindh, Pakistan.
authors.forename: Arjumand
authors.initials: A
authors.lastname: Rizvi
authors.affiliation: Department of Pediatrics and Child Health, Aga Khan University, Karachi, Sindh, Pakistan.
authors.forename: Farheen
authors.initials: F
authors.lastname: Quadri
authors.affiliation: Section of Cardiology, Department of Medicine, Aga Khan University, Karachi, Sindh, Pakistan.
authors.forename: Fateh Ali
authors.initials: FA
authors.lastname: Tipoo
authors.affiliation: Section of Hematology and Oncology, Department of Medicine, Aga Khan University, Karachi, Sindh, Pakistan.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Khurshid
authors.affiliation: Department of Radiology, Aga Khan University, Karachi, Sindh, Pakistan.
authors.forename: Zaffar
authors.initials: Z
authors.lastname: Sajjad
authors.affiliation: Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Colan
authors.affiliation: Department of Pediatrics and Child Health, Aga Khan University, Karachi, Sindh, Pakistan.
authors.forename: Babar S
authors.initials: BS
authors.lastname: Hasan
mesh_terms: D000293:Adolescent; D017311:Amlodipine / Q000008:administration & dosage*; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D009202:Cardiomyopathies / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D002614:Chelating Agents / Q000008:administration & dosage; D002648:Child; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011446:Prospective Studies; D012720:Severity of Illness Index; D013318:Stroke Volume; D013789:Thalassemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002614:Chelating Agents; D017311:Amlodipine; D007501:Iron