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Journal Article Epublish 3 citations

PubMed: 39717517 DOI: 10.1016/j.conctc.2024.101404

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.

Contemp Clin Trials Commun 42:101404

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, Richard Idro, Nancy S Green

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, USA.
  • Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, USA.
  • Department of Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  • Department of Pediatrics, Columbia University Irving Medical Center, 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 reduce SCVI resulting in potential impact on reducing stroke and cognitive dysfunction. We aim to test the impact of daily hydroxyurea therapy on these outcomes in Ugandan children with SCA. We hypothesized 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 in 270 children with SCA (HbSS) in Uganda, ages 3-9 years. Following baseline assessments, participants began hydroxyurea therapy and are followed according to 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. At trial midpoint (18 months) and completion (36 months), outcomes of age-specific assessments will be compared to baseline, as well as biomarkers of anemia, inflammation and malnutrition (secondary outcomes) to determine their relationships to primary outcomes.

Conclusion

This 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 critical insight into the role of hydroxyurea therapy on critical manifestations of SCVI in children with SCA.

Trial registration

https://clinicaltrials.gov/ct2/show/NCT04750707 (registered 11 February 2021).

Protocol version

BRAIN SAFE II Protocol Version 3.0, Mar 02, 2022.

MeSH

Cells, Stroke, Anemia, Sickle Cell, Anemia, Brain, Cognitive Dysfunction, Therapeutics, Child, Hydroxyurea

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