Risk Clinical Stratification of Sickle Cell Disease in Nigeria, Assessment of Efficacy/Safety of Hydroxyurea Treatment
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 4 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: hydroxyurea 500mg of hydroxyurea/day during 6 months |
Drug: hydroxyurea
Other Names:
|
No Intervention: No treatment No hydroxyurea treatment during 6 months |
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
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Absolute neutrophil count >1,500/mircoliter
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Platelet count >95,000/microliter
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Serum creatinine <1.2 mg/dL
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Alanine transaminase less than two times the upper limit of normal
Exclusion Criteria:
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HIVpositive
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Hepatitis B and/or C positive
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Ibadan College of Medicine | Ibadan | Oyo State | Nigeria |
Sponsors and Collaborators
- Loyola University
- University of Illinois at Chicago
- University of Ibadan
Investigators
- Principal Investigator: Bamidele O Tayo, PhD, Loyola University Chicago
- Principal Investigator: Victor R Gordeuk, MD, University of Illinois at Chicago
- Principal Investigator: Titilola S Akingbola, MBBS, FWACP, University of Ibadan College of Medicine, Nigeria
- Principal Investigator: Richard S Cooper, MD, Loyola University Chicago
- Principal Investigator: Lewis Hsu, MD, University of Illinois at Chicago
Study Documents (Full-Text)
None provided.More Information
Publications
- 205449