Hydroxyurea Therapy for Neurological and Cognitive Protection in Pediatric Sickle Cell Anemia in Uganda ( BRAINSAFE-II )
Status:
Recruiting
Trial end date:
2024-08-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 3
Details
Lead Sponsor:
Global Health Uganda LTD
Collaborators:
Columbia University Emory University Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Makerere University Mulago Hospital, Uganda University of Pittsburgh