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: 0
• Participant gender: All

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
• Accepts Healthy Volunteers?: No

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
• Treatments: Hydroxyurea

Criteria

Inclusion Criteria:

1. Documented laboratory diagnosis of HbSS or HbS-B 0 thalassemia (both types are treated equally in SCA studies)

2. Ages 3 through 9 years (inclusive) at enrolment

3. To ensure clinic follow-up, child has attended Mulago Hospital Sickle Cell Anaemia (SCA)clinic 2 times in the prior 4 years, or at least once in the past 2 years if younger than < 4 years

4. No history of hydroxyurea use for longer than 6 months

5. Parent/legal guardian has provided a written consent (and if child is ≥8 years of age, has provided assent)

Exclusion Criteria:

1. History of neurological abnormality known before age 4 months (to avoid those with non SCA brain injury)

2. Child is currently enrolled in another clinical intervention trial

3. Prior stroke as detected by standard Pediatric NIH Stroke Scale (PedNIHSS) examination

Temporary exclusion criteria

4. Pre-existing hematological toxicity

1. Hemoglobin <4.0 gm/dL

2. Hemoglobin <6.0 gm/dL with Absolute Reticulocyte Count <100 x 10 9/L

3. Absolute Reticulocyte Count <80 x 109/L with Hemoglobin <7.0 gm/dL

4. Platelets <80 x 109/L

5. Absolute Neutrophil Count <1.0 x 109/L

5. Found to be with acute illness at enrolment with fever in last 1 week, respiratory infection, etc.

6. History of a sickle crisis within the prior 2 weeks, or blood transfusion within the past 90 days Participants with temporary exclusion can be enrolled later when stable or the excluding criteria has resolved