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.

Conditions

• Sickle Cell Anemia in Children

Interventions

DRUG

Hydroxyurea

The study intervention will be daily oral Hydroxyurea given in single doses starting at approximately 20mg/kg/day and escalated to a maximum 30mg/kg/day depending on clinical need and according to standard guidelines.

Sponsors & Collaborators

• Columbia University

  collaborator OTHER

• University of Pittsburgh

  collaborator OTHER

• Emory University

  collaborator OTHER

• Mulago Hospital, Uganda

  collaborator OTHER

• Makerere University

  collaborator OTHER

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  collaborator NIH

• Global Health Uganda LTD

  lead OTHER

Principal Investigators

• Richard Idro, PhD · Makerere University

• Nancy Green, MD · Columbia University

Study Design

Allocation

NA

Purpose

PREVENTION

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

3 Years

Max Age

9 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-03-09

Primary Completion

2025-03-10

Completion

2025-03-10

Countries

• Uganda

Study Locations