Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Amlodipine for Myocardial Iron in Thalassemia (AMIT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02065492
Recruitment Status : Completed
First Posted : February 19, 2014
Last Update Posted : June 29, 2017
Sponsor:
Information provided by (Responsible Party):
Dr Babar S Hasan, Aga Khan University

Tracking Information
First Submitted Date  ICMJE February 17, 2014
First Posted Date  ICMJE February 19, 2014
Last Update Posted Date June 29, 2017
Study Start Date  ICMJE February 2014
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 18, 2014)
Efficacy of amlodipine in retarding rate of myocardial iron deposition (Assessed by change in T2* times) [ Time Frame: At baseline, and then at 6 months and 12 months from the start of the study ]
Each patient will be randomized into either of two study arms: amlodipine plus chelation or chelation alone. All patients will undergo MRI and T2* imaging at baseline and then at 6 and 12 month follow-up visits. Efficacy of Amlodipine will be assessed using change in T2* times.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 18, 2014)
  • Effect of amlodipine therapy on left ventricular size, systolic and diastolic function [ Time Frame: At baseline and then at 6 months and 12 months from the start of the study ]
    Cardiac MRI and echocardiogram will be utilized to assess both systolic and diastolic function. Basic parameters such as left ventricular end diastolic volume, left ventricular systolic volume and the ejection fraction will be measured. Mitral Inflow Doppler as well as Tissue Doppler Imaging will be used to assess diastolic dysfunction. Conventional Pulsed Doppler Echocardiography will be utilized to derive the myocardial performance index (Tei Index) of each patient which will serve as a surrogate for systolic function. Peak global and segmental longitudinal left and right ventricular strain and strain rate will be calculated using speckle tracking by tracing images obtained from the apical 4-chamber view. Peak global and segmental right and left ventricular circumferential strain and strain rate will also be calculated from a parasternal, mid-cavity short axis view using speckle tracking also.
  • Efficacy of amlodipine in retarding liver iron content (mg/g) [ Time Frame: At baseline and then at 6 months and 12 months from the start of the study ]
    Liver iron content will be measured using T2* imaging of the liver
  • Adverse effects of amlodipine therapy [ Time Frame: At baseline and at 6 months and 12 months from the start of the study; at all visits to the Clinical Trial Unit pharmacy at the Aga Khan Hosptal for dispensing amlodipine and at all routine visits to the outpatient hematology clinic ]
    Data on adverse effects will be be collected using the adverse event form. The adverse effects anticipated include fatigue, nausea, edema, palpitations, flushing, headache, dizziness, blurred vision, somnolence, cough, hypertension and sinus bradycardia. Any other adverse event will also be reported. Adverse events that require only symptomatic management will be treated by the participant's primary hematologist. Adverse events that require hospitalization will also be managed by the participant's primary hematologist and the costs incurred will be covered by the research fund. Cardiovascular adverse events that require outpatient or inpatient management will be treated by the Principal Investigator and his cardiology team and all costs incurred will be covered by the research fund.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Amlodipine for Myocardial Iron in Thalassemia
Official Title  ICMJE Effect of L-type Calcium Channel Blocker (Amlodipine) on Myocardial Iron Deposition in Thalassemic Patients With Moderate to Severe Myocardial Iron Deposition: A Randomized Pilot Study
Brief Summary Children with thalassemia may have high iron levels after receiving blood transfusions. These high iron levels can have damaging effects on the body, especially the heart. Conventionally only chelation therapy was given for prevention of iron buildup in the heart. However, current research has shown that another drug, amlodipine, also helps to slow down the deposition of iron in the heart. This study is designed to see if patients receiving amlodipine along with their regular chelation therapy have a slower rate of iron buildup in the heart when compared with patients who are receiving chelation only.
Detailed Description

Null Hypothesis There is no difference between the efficacy of chelation plus amlodipine therapy and chelation therapy alone in retarding the rate of myocardial iron deposition in thalassemia patients with iron overload and a constant transfusion need.

Alternate Hypothesis Chelation plus amlodipine therapy is more efficacious than chelation therapy alone in retarding the rate of myocardial iron deposition in thalassemia patients with iron overload and a constant transfusion need.

The aim of the investigators study is to determine if amlodipine, an L-type specific calcium channel blocker, in addition to the standard aggressive chelation therapy, can retard the deposition of iron in the myocardium of thalassemia patients with significant myocardial iron load with or without cardiomyopathy.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Thalassemia
Intervention  ICMJE
  • Drug: Standard Chelation
    This will comprise of standard chelation drugs (Deferasirox or Deferoxamine or Combination of Deferoxamine and Deferiprone).The dosage and drug used will depend on ferritin levels and individual requirement, as determined by the treating hematologist and will be in accordance with the Iron chelation guidelines from Pakistan Thalassemia Society.
    Other Name: Asunra or Kelfer or Desferal
  • Drug: Amlodipine
    doses of 0.2 to 0.25 mg/kg/day PO would be given during this trial
    Other Name: L-type calcium channel blocker
Study Arms  ICMJE
  • Experimental: Standard Chelation & Amlodipine

    This arm will receive both chelation and amlodipine.

    Amlodipine will be administered as a single daily dose. It will be administered at a dose of 0.1 mg/kg/day or maximum of 2.5 mg/day.

    Standard Chelation therapy will be administered either by subcutaneous infusion of Deferoxamine (3-5 days a week) or oral Deferasirox (daily) or combination of Deferoxamine and Deferiprone.

    The dosage will depend on individual requirement, as determined by the treating hematologist.

    Interventions:
    • Drug: Standard Chelation
    • Drug: Amlodipine
  • Active Comparator: Standard Chelation

    Deferasirox or Deferoxamine or Deferiprone. Patients in this arm will be administered only standard chelation therapy,either by subcutaneous infusion of Chelation therapy of Deferoxamine (3-5 days a week) or oral Deferasirox (daily) or combination of Deferoxamine and Deferiprone.

    The dosage will depend on individual requirement, as determined by the treating hematologist.

    This will serve as the control arm of the study without any additional intervention.

    Intervention: Drug: Standard Chelation
Publications * Shakoor A, Zahoor M, Sadaf A, Alvi N, Fadoo Z, Rizvi A, Quadri F, Tipoo FA, Khurshid M, Sajjad Z, Colan S, Hasan BS. 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. BMJ Open. 2014 Dec 8;4(12):e005360. doi: 10.1136/bmjopen-2014-005360.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 18, 2014)
20
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2015
Actual Primary Completion Date October 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Pediatric patients aged ≥ 6 and ≤ 20 years managed at AKUH for at least 1 year
  • ≥ 10 blood transfusion in life time
  • Transfusion need ≥ 180 ml/kg/year
  • Serum ferritin ≥ 1000 ug/dl
  • Patient deemed capable of receiving chelation therapy (by treating hematologist) either subcutaneous infusion of Deferoxamine (Desferal) (3-5 days a week) or oral deferasirox (daily) or Defeperione (oral) or a combination of Desferal and Defeperione.
  • Patients who have been on a stable chelation regimen ≥ 6 months
  • Completed and signed Informed consent/assent.

Exclusion Criteria:

  • Patients with known hypersensitivity to amlodipine.
  • Patients with known sinoatrial nodal disease or aortic stenosis.
  • Patients with known severe myocardial dysfunction, defined as A LV ejection fraction of ≤ 4 SD for age even without symptoms.
  • Patients with known signs and symptoms of heart failure.
  • Patients with a T2* value of < 4 ms on cardiac MRI.
  • Patients with systolic blood pressures ≤ 2 SD for age (systemic hypotension) at the time of enrolment.
  • Patients with previously diagnosed significant congenital heart diseases or acquired heart diseases other than thalassemia (as defined earlier).
  • Patients with known contraindications to MRI (pacemakers, cerebral aneurysm metal clips, etc.)
  • Patient with a known history of developing tetany after use of a calcium channel blocker
  • Known pregnancy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 20 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Pakistan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02065492
Other Study ID Numbers  ICMJE AMIT
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Dr Babar S Hasan, Aga Khan University
Study Sponsor  ICMJE Aga Khan University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Babar Hasan Aga Khan University
PRS Account Aga Khan University
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP