Clinical Trial: Amlodipine for Myocardial Iron in Thalassemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Effect of L-type Calcium Channel Blocker (Amlodipine) on Myocardial Iron Deposition in Thalassemic Patients With Moderate to Severe Myocardial Iron D

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 Summary:

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.


Sponsor: Aga Khan University

Current Primary Outcome: 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: Same as current

Current Secondary Outcome:

  • 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: Same as current

Information By: Aga Khan University

Dates:
Date Received: February 17, 2014
Date Started: February 2014
Date Completion:
Last Updated: December 28, 2015
Last Verified: December 2015