Hydroxyurea Therapy for Neurological and Cognitive Protection in Pediatric Sickle Cell Anemia in Uganda ( BRAINSAFE-II )

Summary

Worldwide, an estimated 200,000 babies are born with Sickle Cell Anemia (SCA) annually. Affected children suffer chronic ill health with some having frequent hospitalization. The patients are also at a high risk of brain injury arising from small and large cerebral blood vessel damage in SCA, also called sickle cell vasculopathy (SCV). SCV is associated with the high risk of stroke. Such injury may manifest with neurological and cognitive impairment. An abnormal blood flow to the brain, as measured by a Doppler Ultrasound scan is a known risk factor for stroke. The hypothesis is that hydroxyurea therapy will prevent, stabilize or improve SCV and its effects. The study is an open label, single arm clinical trial to test the impact of hydroxyurea treatment in 270 children with SCA starting at ages 3-9 years. Following baseline assessments, all participants will begin hydroxyurea therapy starting at about 20mg/kg/day. Changes in the frequency and severity of each test (neurological and cognitive tests and cerebral blood flow velocity) will be compared with their baseline tests (prior to hydroxyurea) by repeating these tests at 18 and 36 months. In a randomly selected subset of 90 participants, an evaluation of the impact of hydroxyurea on structural brain vascular injury using magnetic resonance brain imaging (MRI) and magnetic vessel imaging ,also called angiography (MRA) at baseline and at 36 months. Lastly, an assessment of changes to biomarkers of anemia, inflammation and malnutrition from before and during hydroxyurea therapy and determine their relationship to the outcomes. The proposed intervention with hydroxyurea is the first Africa-based trial to broadly prevent or ameliorate manifestations of SCV.

Timeline

Start

2021-03-09

Primary completion

2025-03-10

Completion

2025-03-10

Publications

• Background Galadanci NA, Umar Abdullahi S, Vance LD, Musa Tabari A, Ali S, Belonwu R, Salihu A, Amal Galadanci A, Wudil Jibir B, Bello-Manga H, Neville K, Kirkham FJ, Shyr Y, Phillips S, Covert BV, Kassim AA, Jordan LC, Aliyu MH, DeBaun MR. Feasibility trial for primary stroke prevention in children with sickle cell anemia in Nigeria (SPIN trial). Am J Hematol. 2017 Aug;92(8):780-788. doi: 10.1002/ajh.24770. Epub 2017 Jun 15.
• Naggayi SK, Kalibbala D, Mboizi V, Ssenkusu J, Jin Z, Rosano C, Munube D, Wambaka B, Namazzi R, Kasirye P, Kabatabaazi M, Nambatya G, Murungi S, Nabaggala C, Nakafeero M, Troidl IR, Opoka R, Idro R, Bangirana P, Green NS. Neurocognitive gains among Ugandan children with sickle cell anemia on hydroxyurea: 18-month interim trial results. Blood Adv. 2025 Jun 24;9(12):3116-3127. doi: 10.1182/bloodadvances.2024015073.
• Mboizi V, Nabaggala C, Munube D, Ssenkusu JM, Kasirye P, Kamya S, Kawooya MG, Boehme A, Minja F, Mupere E, Opoka R, Rosano C, Idro R, Green NS. 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. 2024 Nov 28;42:101404. doi: 10.1016/j.conctc.2024.101404. eCollection 2024 Dec.

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