Amlodipine for Myocardial Iron in Thalassemia - Clinical Trial for Thalassemia | NCT02065492

Back to results

Primary Purpose

Status

Completed

Phase

Phase 2

Locations

Pakistan

Study Type

Interventional

Intervention

Standard Chelation

Amlodipine

About this trial

This is an interventional prevention trial for Thalassemia focused on measuring Thalassemia, Amlodipine, Chelation, T2*, MRI, Myocardial Iron

Eligibility Criteria

6 Years - 20 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Aga Khan University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Standard Chelation & Amlodipine

Standard Chelation

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Efficacy of amlodipine in retarding rate of myocardial iron deposition (Assessed by change in T2* times)

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

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)

Liver iron content will be measured using T2* imaging of the liver

Adverse effects of amlodipine therapy

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.

Full Information

NCT ID

NCT02065492

First Posted

February 17, 2014

Last Updated

June 28, 2017

Sponsor

Aga Khan University

1. Study Identification

Unique Protocol Identification Number

NCT02065492

Brief Title

Amlodipine for Myocardial Iron in Thalassemia

Acronym

AMIT

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 Type

Interventional

2. Study Status

Record Verification Date

June 2017

Overall Recruitment Status

Completed

Study Start Date

February 2014 (undefined)

Primary Completion Date

October 2015 (Actual)

Study Completion Date

November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Aga Khan University

4. Oversight

Data Monitoring Committee

No

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Thalassemia

Keywords

Thalassemia, Amlodipine, Chelation, T2*, MRI, Myocardial Iron

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Standard Chelation & Amlodipine

Arm Type

Experimental

Arm Description

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.

Arm Title

Standard Chelation

Arm Type

Active Comparator

Arm Description

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 Type

Drug

Intervention Name(s)

Standard Chelation

Other Intervention Name(s)

Asunra or Kelfer or Desferal

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Amlodipine

Other Intervention Name(s)

L-type calcium channel blocker

Intervention Description

doses of 0.2 to 0.25 mg/kg/day PO would be given during this trial

Primary Outcome Measure Information:

Title

Efficacy of amlodipine in retarding rate of myocardial iron deposition (Assessed by change in T2* times)

Description

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.

Time Frame

At baseline, and then at 6 months and 12 months from the start of the study

Secondary Outcome Measure Information:

Title

Effect of amlodipine therapy on left ventricular size, systolic and diastolic function

Description

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.

Time Frame

At baseline and then at 6 months and 12 months from the start of the study

Title

Efficacy of amlodipine in retarding liver iron content (mg/g)

Description

Liver iron content will be measured using T2* imaging of the liver

Time Frame

At baseline and then at 6 months and 12 months from the start of the study

Title

Adverse effects of amlodipine therapy

Description

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.

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Maximum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

No

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Babar Hasan

Organizational Affiliation

Aga Khan University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Aga Khan University Hospital

City

Karachi

State/Province

Sindh

ZIP/Postal Code

74800

Country

Pakistan

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

25492271

Citation

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.

Results Reference

derived

Amlodipine for Myocardial Iron in Thalassemia (AMIT)

Thalassemia

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial