Please select the eligibility criteria that correspond to the clinical trial below.
Title: Amlodipine in the Prevention and Treatment of Iron Overload in Patients With Thalassemia Major: a Randomized, Controlled Trial
Brief Summary: This study aims to investigate the use of amlodipine, a drug that blocks the uptake of calcium into cells, in the prevention and treatment of iron overload in patients with thalassemia major. Since iron uses the same calcium channels to enter the heart, pancreas and other organs, blocking these channels might help to prevent the accumulation of iron in these tissues. The study will follow 60 patients with thalassemia major: 30 will receive amlodipine and 30 will serve as controls receiving placebo in a randomized double-blind fashion. Patients will be monitored through one year. Monitoring will occur through the measurement of blood ferritin as well as live and heart T2\* by MRI initially, at 6 and 12 months.


Options:
A: Inclusion Criteria:

* Thalassaemia Major
* Patient must have had a cardiac MRI scan between 1999 and 2006

Exclusion Criteria:

* Other structural heart disease such as valvular abnormalities, MI, congenital heart disease
B: Inclusion Criteria:

* Transfusional iron overload due to: hereditary anemias such as sickle cell disease, β-thalassemia and Diamond-Blackfan anemia; acquired anemias such as Myelodysplastic Syndrome and other forms of bone marrow failure. Patients must also be transfusion-dependent and require chronic treatment with deferoxamine, deferasirox, and/or deferiprone.
* Willing to discontinue all existing iron chelation therapies throughout study period.
* Serum ferritin greater than 500 ng/mL at Screening.
* Baseline liver iron concentration and cardiac MRI T2\* per protocol requirements.
* Mean of the previous three pre-transfusion hemoglobin concentrations greater than or equal to 7.5 g/dL.
* Agrees to use an approved method of contraception throughout study period.

Exclusion Criteria:

* As a result of medical review, physical examination or Screening investigations, the Principal Investigator considers the patient unfit for the study.
* Non-elective hospitalization within the 30 days prior to Baseline testing. (Patients with sickle cell anemia who are admitted to the hospital for management of sickle crisis pain whose uncomplicated hospital course was four days or less and who, 14 days prior to Baseline testing, have returned to their previous health status are acceptable.)
* Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow or skin disorder as determined by the Investigator.
* Evidence of significant renal insufficiency; possible examples include: serum creatinine above the upper limit of normal, proteinuria greater than 2 gm per day or calculated creatinine clearance of less than 60 mL/minute.
* Cardiac left ventricular ejection fraction outside of protocol requirements.
* Known sensitivity to magnesium stearate, croscarmellose sodium or FBS0701.
* Platelet count below 100,000/µL and/or absolute neutrophil count less than 1500/mm3 at Screening and \<50% at Baseline testing by MRI
* Alkaline phosphatase, AST or ALT outside of protocol requirements.
* Liver Function Tests: ALT \>5 times the local upper limit of normal on two occasions in the previous 12 months or ALT at Screening \>200 IU/L
* Use of any investigational agent within the 30 days prior to the Baseline testing.
C: Inclusion Criteria:

1. Patients with thalassemia major with at least 6 years of age undergoing iron chelation therapy.
2. No anticipated changes in chelation regimen for the next 12 months
3. Completed and signed Informed Consent

Exclusion Criteria:

1. Pregnancy
2. Advanced class III/IV heart failure or LVEF \< 0.35% (by MRI)
3. Formal contra-indications to MRI (pacemakers, cerebral aneurysm metal clips, etc).
4. Advanced heart AV block
D: 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.

Answer: C