The investigators suspect that significant degrees of iron overload in subjects with SCD
result in decreased red cell survival, abnormal endothelial function and markedly
dysregulated autonomic function. Furthermore, the investigators anticipate that the
magnitude of these effects is proportional not only to the magnitude of total body iron
stores but also to the duration of exposure to the high iron levels in tissues.
Primary objective To determine if red cell survival as assessed by 51Cr red cell survival
analysis, hemoglobin level, reticulocyte count, lactic acid dehydrogenase, and plasma
hemoglobin in sickle cell patients is related to the degree of iron overload.
1. Determine if the magnitude of endothelial-dependant vasodilation is related to The
degree of iron overload.
2. Determine if the degree of change in cardiac beat to beat variability in response to
hypoxic exposure or to cold exposure ("cold-face-test") is related the magnitude of
The primary measure of iron overload will be MRI determination of liver iron concentration.
||Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
|Ages Eligible for Study:||14 Years|
|Genders Eligible for Study:||Both|
|Accepts Healthy Volunteers:||No|
- Male or female patients with sickle cell anemia (SS or SB thalassemia) with
transfusional iron overload.
- Currently not on chronic or frequent transfusion
- Age equal or greater then 14 years
- Patients with iron overload from repeated blood transfusion, as defined by one of the
1. For patients greater then 16 years old receiving simple transfusions: estimated
lifetime history of receipt of at least 100 ml/kg or 15 adult units of packed
red blood cells, OR
2. For patients equal to or less then 16 years old receiving simple transfusions:
estimated lifetime history of receipt of at least 100 ml/kg of packed red blood
3. For any patient: liver iron content equal/greater then 3 mg Fe/g dw as measured
by biopsy or magnetic resonance imaging who have not been adequately chelated
since that measurement, OR
4. a serum ferritin equal/greater then 1000 ng/mL on at least two occasions, at
least two weeks apart, during the prior year. Samples must be obtained in the
absence of concomitant infection
- Life expectancy equal/greater then 12 months
- Sexually active women must use an effective method of contraception, or must have
undergone clinically documented total hysterectomy and/or oophorectomy, or tubal
ligation or be postmenopausal (defined as amenorrhea for at least 12 months)
Inclusion criteria for treatment pilot study
- Meets all inclusion criteria for screening
- LIC by MRI greater than or equal to 8 mg/g.
- Blood transfusion within 12 weeks of the day 0 hemolysis labs
- Currently requires blood transfusion more than three times a year.
- Contraindication to MRI, including cardiac pacemaker, brain aneurysm clip, implanted
neurostimulator, insulin pump, cochlear implant, metal slivers in the eyes,
intrauterine device or any other MRI incompatible metal implants or intractable
- Serum creatinine above the upper limit of normal
- Concomitant treatment with erythropoietin or its analogs.
- AST or ALT greater then 250 U/L during screening (patients may be re-screened at a
later date if the cause of the elevation is known to be due to a transient process).
- Patients receiving currently on chelation will be asked to stop for one week before
starting or restarting Exjade. (a equal/greater then 1 week washout period prior to
first dose of study drug is required)
- History of HIV positive test result (ELISA or Western blot)
- History of drug or alcohol abuse within the 12 months prior to enrollment
- Patients with uncontrolled systemic hypertension
- Severe cardiac insufficiency (NYHA III or IV), with uncontrolled and/or unstable
cardiac or coronary artery disease not controlled by standard medical therapy
- Patients with a diagnosis of or history of clinically relevant ocular toxicity
related to iron chelation
- Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent study
- Pregnancy (as documented in required screening laboratory test) or breast feeding
- Patients who received treatment with systemic investigational drug within the past 4
weeks or topical investigational drug within the past 7 days or are planning to
receive other investigational drugs while participating in the study
- Other surgical or medical condition which might significantly alter the absorption,
distribution, metabolism or excretion of study drug
- History of non-compliance to medical regimens or patients who are considered
potentially unreliable and/or not cooperative