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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Thalassemia	Drug: Standard Chelation Drug: Amlodipine	Phase 2 Phase 3

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 Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	20 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	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
Study Start Date :	February 2014
Actual Primary Completion Date :	October 2015
Actual Study Completion Date :	November 2015

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: African iron overload

MedlinePlus related topics: Iron Thalassemia

Drug Information available for: Amlodipine Amlodipine besylate

Genetic and Rare Diseases Information Center resources: Thalassemia Siderosis

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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.	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
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.	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

Arm

Intervention/treatment

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.

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

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.

Drug: Standard Chelation

Other Name: Asunra or Kelfer or Desferal

Outcome Measures

Primary Outcome Measures :

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.

Secondary Outcome Measures :

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.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	6 Years to 20 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02065492

Locations

Layout table for location information

Pakistan
Aga Khan University Hospital
Karachi, Sindh, Pakistan, 74800

Sponsors and Collaborators

Aga Khan University

Investigators

Layout table for investigator information

Principal Investigator:	Babar Hasan	Aga Khan University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Layout table for additonal information

Responsible Party:	Dr Babar S Hasan, Assistant Professor, Aga Khan University
ClinicalTrials.gov Identifier:	NCT02065492
Other Study ID Numbers:	AMIT
First Posted:	February 19, 2014 Key Record Dates
Last Update Posted:	June 29, 2017
Last Verified:	June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by Dr Babar S Hasan, Aga Khan University:


Thalassemia Amlodipine Chelation	T2* MRI Myocardial Iron

Additional relevant MeSH terms:

Layout table for MeSH terms

Thalassemia Anemia, Hemolytic, Congenital Anemia, Hemolytic Anemia Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn Amlodipine	Calcium Channel Blockers Calcium-Regulating Hormones and Agents Physiological Effects of Drugs Antihypertensive Agents Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Vasodilator Agents

To Top