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Updated: Jul 5, 2025
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Hydroxyurea Therapy for Neurological and Cognitive Protection in Pediatric Sickle Cell Anemia in Uganda (BRAIN SAFE
Vincent Mboizi1, Catherine Nabaggala1, Deogratias Munube2
1Global Health Uganda, Kampala, Uganda.
Insights
Hydroxyurea therapy may prevent sickle cerebrovascular injury (SCVI) in children with sickle cell anemia (SCA). This study in Uganda will assess hydroxyurea
Area of Science:
- Pediatric Neurology
- Hematology
- Clinical Trials
Background:
- Children with sickle cell anemia (SCA) in Sub-Saharan Africa face a high risk of sickle cerebrovascular injury (SCVI).
- Hydroxyurea is a disease-modifying therapy that may reduce SCVI, stroke risk, and cognitive dysfunction in SCA patients.
- The BRAIN SAFE II study investigates the impact of daily hydroxyurea on these outcomes in Ugandan children with SCA.
Approach:
- An open-label, single-arm trial involving 270 Ugandan children (ages 3-9) with SCA (HbSS).
- Participants receive daily hydroxyurea, with dosage escalated to the maximum tolerated dose (MTD).
- Outcomes include cerebral arterial velocity (Doppler ultrasound), neurocognitive testing, and MRI/MRA for structural SCVI in a subset.
Key Points:
- Primary outcomes: cerebral arterial velocity and neurocognitive function assessed at 18 and 36 months.
- Secondary outcomes: structural SCVI, anemia, inflammation, and malnutrition biomarkers.
- Analysis will compare baseline assessments with trial midpoint and completion data.
Conclusions:
- The study aims to determine if hydroxyurea therapy can prevent, stabilize, or improve SCVI and related complications in children with SCA.
- Results will offer crucial insights into hydroxyurea's role in managing SCVI manifestations in this pediatric population.
Background:
Children with sickle cell anemia (SCA) in Sub-Saharan Africa are at high risk of sickle cerebrovascular injury (SCVI). Hydroxyurea, a commonly used disease-modifying therapy, may prevent or decrease SCVI for reduced incident stroke, stroke risk and potentially cognitive dysfunction. We aim to test the impact of daily hydroxyurea therapy on these outcomes in Ugandan children with SCA. We hypothesize that hydroxyurea therapy over 36 months will prevent, stabilize or improve these complications of SCA.
Methods:
The BRAIN SAFE II study is an open-label, single-arm trial of daily hydroxyurea for 270 children with SCA (HbSS) in Uganda, ages 3-9 years. Following baseline assessments, participants began hydroxyurea therapy and clinically followed per local guidelines. Standard hydroxyurea dose is escalated to maximum tolerated dose (MTD). SCVI is assessed by cerebral arterial velocity using Doppler ultrasound, with cognitive function determined by formal neurocognitive testing (primary outcomes). Structural SCVI is assessed by magnetic resonance imaging (MRI) and angiography (MRA) in a sub-sample of 90 participants ages ≥5 years, along with biomarkers of anemia, inflammation and malnutrition (secondary outcomes). At trial midpoint (18 months) and completion (36 months), primary outcomes will be compared to participants' baseline to determine hydroxyurea impact and relationships to secondary outcomes.
Conclusion:
This open-label, single-arm trial will examine the impact of hydroxyurea on preventing or ameliorating SCA SCVI in children, assessed by reducing incident stroke, stroke risk and neurocognitive dysfunction. Trial results will provide important insight into the role of hydroxyurea therapy on critical manifestations of SCVI in children with SCA.
