Long Term Effects of Hydroxyurea Therapy in Children With Sickle Cell Disease

Study Overview
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Brief Summary
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The primary objectives of this prospective, observational study are (1) to describe the long-term cellular, molecular, and clinical effects of hydroxyurea therapy in sickle cell disease, and (2) to perform hydroxyurea pharmacokinetics studies. This study will follow sickle cell patients being treated with hydroxyurea for a long period of time to evaluate the long-term cellular and molecular effects of the drug on the patients' body. This study will consist of two patient groups. One group will be made up of patients who have received hydroxyurea therapy before entering the study. The second group will be made up of patients who have not received hydroxyurea before study entry.

Detailed Description
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Many years of study have documented the severe effects of sickle cell disease. Some of these effects include hemolysis (the break down of red blood cells), blockages in the blood vessels, and damage to the organs systems of the body. Hydroxyurea, which is given by mouth, is used to effectively prevent blockages in the blood vessels of patients with sickle cell disease. The hydroxyurea dosage varies and the responses of the body to this drug are not well understood. This study will follow sickle cell patients being treated with hydroxyurea for a long period of time to evaluate the long-term cellular and molecular effects of the drug on the patients' body. This study will consist of two patient groups. One group will be made up of patients who have received hydroxyurea therapy before entering the study (Old Cohort). The second group will be made up of patients who have not received hydroxyurea before study entry (New Cohort). This is not a therapeutic drug trial. Subjects for this study will receive hydroxyurea therapy for accepted clinical indications, and will be treated per best clinical management using treatment algorithms established at St. Jude Children's Research Hospital and other pediatric sickle cell programs across the United States. Hydroxyurea therapy data (such as dosing and duration of therapy) will not be dictated by this study, but will be collected to correlate with long-term outcomes. Hydroxyurea dose escalation to a stable MTD will occur according to published guidelines.

Official Title
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Long Term Effects of Hydroxyurea Therapy in Children With Sickle Cell Disease

Conditions
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Sickle Cell Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients from birth up to age 30 years Diagnosis of sickle cell disease Patients who are receiving hydroxyurea therapy or plan to begin hydroxyurea therapy

Ages Eligible for Study
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Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients With Prior Hydroxyurea<br>Patients who have received hydroxyurea therapy before entering the study. | |
| Patients Without Prior Hydroxyurea<br>Patients who have not received hydroxyurea before study entry. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DNA damage from hydroxyurea therapy-variable-diversity-joining (VDJ) recombination events defined as the number of events per microgram of genomic DNA; |  | Every 3 years | 
| DNA damage from hydroxyurea therapy-percentage of HJB in immature (CD71+) erythrocytes |  | Every 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain function as measured by MRI/MRA and TCD | optional test | Every 3 years | 
| Splenic function as measured by Spleen Scan | optional test | Every 3 years | 
| Kidney function as measured by BUN/creatinine and Urinalysis, glomerular filtration rate (GFR) | optional test | Every 3 years | 
| Lung function as measured by forced vital capacity (FVC) (%), forced vital volume in 1 second (FVC1) (%), and tricuspid regurgitation (TR) jet on Echocardiogram (ECHO) | collected if performed for clinical purposes | Every 3 years | 
| Growth as measured by height and weight |  | Every visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hydroxyurea, Sickle Cell Anemia