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PubMed: 38260320 DOI: 10.1101/2024.01.12.24301208
Hydroxyurea Therapy for Neurological and Cognitive Protection in Pediatric Sickle Cell Anemia in Uganda (BRAIN SAFE II): Protocol for a single-arm open label trial.
medRxiv
Authors: Vincent Mboizi, Catherine Nabaggala, Deogratias Munube, John M Ssenkusu, Phillip Kasirye, Samson Kamya, Michael G Kawooya, Amelia Boehme, Frank Minja, Ezekiel Mupere, Robert Opoka, Caterina Rosano, Nancy S Green, Richard Idro
Affiliations
- Global Health Uganda, Kampala, Uganda.
- Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda.
- Department of Epidemiology and Biostatistics, Makerere University School of Public Health, Kampala, Uganda.
- Ernest Cook Ultrasound Research and Education Institute (ECUREI), Mengo Hospital, Kampala, Uganda.
- Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, USA.
- Department of Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
- Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA.
Abstract
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.
MeSH
Stroke, Anemia, Sickle Cell, Risk, Child, Brain, Hydroxyurea, Cells, Therapeutics