ThalassemiaPhase 2/3AMITNCT02065492
Amlodipine for Myocardial Iron in Thalassemia
A Phase 2/3 study testing Standard Chelation and Amlodipine in people with Thalassemia, run by Aga Khan University at 1 site in Pakistan.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 20 years
- Conditions the study is for
- Thalassemia
- What is being tested?
- Standard Chelation and Amlodipine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 sitePakistan
- Study dates
- Feb 2014to Nov 2015
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Thalassemia
- Being tested
- Standard Chelation, Amlodipine
- Keywords
- Thalassemia, Amlodipine, Chelation, T2*, MRI, Myocardial Iron
- Medical subject headings
- Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard ChelationDrug
Also called Asunra or Kelfer or Desferal
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.
AmlodipineDrug
Also called L-type calcium channel blocker
doses of 0.2 to 0.25 mg/kg/day PO would be given during this trial
| Study group | Role | What they receive |
|---|---|---|
| Standard Chelation & Amlodipine | Experimental | 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. Receives: Drug: Standard Chelation; Drug: Amlodipine |
| Standard Chelation | Active comparator | 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. Receives: Drug: Standard Chelation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At baseline, and then at 6 months and 12 months from the start of the study
Secondary outcomes (3)
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.
Measured: At baseline and then at 6 months and 12 months from the start of the study
Efficacy of amlodipine in retarding liver iron content (mg/g)
Liver iron content will be measured using T2* imaging of the liver
Measured: At baseline and then at 6 months and 12 months from the start of the study
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2014 (estimated)
- Study startFeb 2014
- Primary completionOct 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ThalassemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aga Khan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Babar S Hasan, Aga Khan University
- Investigators
- Babar Hasan, Principal investigator, Aga Khan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02065492
- Sponsor's protocol ID
- AMIT
- Acronym
- AMIT
- Status last verified
- Jun 2017
- First submitted
- 17 Feb 2014
- Last updated
- 29 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Padhani ZA, Gangwani MK, Sadaf A, Hasan B, Colan S, Alvi N, Das JK. Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. Cochrane Database Syst Rev. 2023 Nov 17;11(11):CD011626. doi: 10.1002/14651858.CD011626.pub3.
PubMed 37975597Shakoor 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.
PubMed 25492271
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02065492
- Acronym / sponsor ID
- AMIT / AMIT
- Conditions
- Thalassemia
- Keywords
- Thalassemia, Amlodipine, Chelation, T2*, MRI, Myocardial Iron
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Aga Khan UniversityUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- Oct 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 19 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Chelation & Amlodipine | Experimental | Drug: Standard Chelation, Drug: AmlodipineThis 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. |
| Standard Chelation | Active comparator | Drug: Standard ChelationDeferasirox 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. |
Who may qualify
- Ages
- 6 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard ChelationAlso: Asunra or Kelfer or DesferalThis 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. | Drug | Standard Chelation, Standard Chelation & Amlodipine |
| AmlodipineAlso: L-type calcium channel blockerdoses of 0.2 to 0.25 mg/kg/day PO would be given during this trial | Drug | Standard Chelation & Amlodipine |
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.
3 secondary outcomes
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2017.
- Derived from this study: PubMed 37975597Padhani ZA, Gangwani MK, Sadaf A, Hasan B, Colan S, Alvi N, Das JK. Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. Cochrane Database Syst Rev. 2023 Nov 17;11(11):CD011626. doi: 10.1002/14651858.CD011626.pub3.
- Derived from this study: PubMed 25492271Shakoor 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Babar Hasan principal investigator
Aga Khan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Standard Chelation and Amlodipine in people with Thalassemia, run by Aga Khan University at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02065492, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2017.