Sickle Cell Anemia, Sickle Cell Disease
Conditions
Keywords
sickle cell disease, sickle cell anemia, hydroxyurea, Nigeria, low income country, middle income country, developing country
Brief summary
The vast majority of births with sickle cell disease (SCD) occur in Africa and 90% are thought to die before the age of five. Hydroxyurea (HU) is the only drug approved by the FDA for the treatment of sickle cell anemia. Although HU is used to treat small numbers of patients in Africa, cost, fear of toxicity, and lack of awareness and availability limit its use. The leukopenia that may be seen with HU raises the possibility of increased susceptibility to infection. Risk stratification - i.e., identification of patients most likely to benefit- could focus therapy and provide confidence that the risk:benefit ratio is favorable. Several clinical measures of future risk are well defined and findings on modifier genes in the US, primarily related to fetal hemoglobin (HbF), have further improved risk prediction. Whether the genetic variants predict severity in Africa is not known. The investigators have established a SCD cohort in Ibadan, Nigeria. In the first phase of this research the investigators will implement clinical risk examinations and assess the relationship between clinical characteristics (including levels of HbF) and known genetic markers. As a proxy for a birth cohort, the investigators will compare the frequency of the genetic markers in adult patients (i.e., survivors) to children. In the second phase the investigators will randomize 40 high risk adult patients to fixed low dose HU or no HU treatment in a crossover design and monitor hematologic and physiologic parameters to document hematologic effects and safety. This work will lay the basis for a large-scale trial to document safety and efficacy.
Interventions
DRUGhydroxyurea
Sponsors
University of Illinois at Chicago
University of Ibadan
Loyola University
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Adult patients to start to receive fixed low dose hydroxyurea (10 mg/kg) per day for six months and then crossover to no hydroxyurea treatment for six months, or start with no hydroxyurea treatment for six months and then crossover to receive fixed low dose hydroxyurea (10 mg/kg) per day for six months.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>= 18 years * HemoglobinSS (HbSS) or beta-zero (B0) thalassemia genotype * Hemoglobin concentration \>4.5 g/dL at steady state and time of enrollment * Absolute neutrophil count \>1,500/mircoliter * Platelet count \>95,000/microliter * Serum creatinine \<1.2 mg/dL * Alanine transaminase less than two times the upper limit of normal
Exclusion criteria
* HIVpositive * Hepatitis B and/or C positive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cytopenia | every 2 weeks during a period of 6 months | Neutrophil count \<500/microliter, platelet count \<50,000 or a reticulocyte count\<95,000 with Hemoglobin of 9.0 g/dL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Development of infection evaluated by a physician at the point of care | every 2 weeks for period of 6 months | Infections such as malaria or tuberculosis, which may be newly acquired or recrudescent. |
Other
| Measure | Time frame | Description |
|---|---|---|
| laboratory values of Hemoglobin F%, hemoglobin concentration, reticulocyte count, mean corpuscular volume and white blood cell count. | baseline, 3 months and 6 months. | — |
| Clinical complications such as acute pain episode, acute chest syndrome and need for blood transfusion. | every 2 weeks for a period of 6 months. | Evaluated by a nurse or physician at point of care. |
Countries
Nigeria
Outcome results
None listed