Risk Clinical Stratification of Sickle Cell Disease in Nigeria, Assessment of Efficacy/Safety of Hydroxyurea Treatment

Sponsor

Loyola University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02149537

Collaborator

University of Illinois at Chicago (Other), University of Ibadan (Other)

Enrollment

Location

Arms

Duration (Months)

0.6

Patients Per Site Per Month

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
Sickle Cell Disease Sickle Cell Anemia	Drug: hydroxyurea	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

53 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Risk Stratification for Clinical Severity of Sickle Cell Disease in Nigeria and Assessment of Efficacy and Safety During Treatment With Hydroxyurea

Study Start Date :

Dec 1, 2014

Actual Primary Completion Date :

Sep 1, 2017

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: hydroxyurea 500mg of hydroxyurea/day during 6 months	Drug: hydroxyurea Other Names: Hydroxycarbamide
No Intervention: No treatment No hydroxyurea treatment during 6 months

Arm

Intervention/Treatment

Experimental: hydroxyurea

500mg of hydroxyurea/day during 6 months

Drug: hydroxyurea

Other Names:

Hydroxycarbamide

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

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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