Sickle Cell Anemia in Children Clinical Trial
— BRAINSAFEIIOfficial title:
Hydroxyurea Therapy for Neurological and Cognitive Protection in Pediatric Sickle Cell Anemia in Uganda: A Single Arm Open Label Trial, "BRAIN SAFE II"
Verified date | August 2023 |
Source | Global Health Uganda LTD |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 270 |
Est. completion date | June 30, 2024 |
Est. primary completion date | June 30, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 3 Years to 9 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Uganda | Global Health Uganda | Kampala |
Lead Sponsor | Collaborator |
---|---|
Global Health Uganda LTD | Columbia University, Emory University, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Makerere University, Mulago Hospital, Uganda, University of Pittsburgh |
Uganda,
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. Erratum In: Am J Hematol. 2018 Mar;93(3):E83. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | The frequency, age specific prevalence and severity of Sickle Cell Vasculopathy manifested by New stroke as assessed by the Pediatric NIH Stroke Scale (PedNIHSS) over the 3-year study while on hydroxyurea treatment, compared to baseline assessments. | Baseline assessment will be completed for all study participants and over the 3-year study, scheduled outcome assessments will be performed at study months 18 and 36.
These assessments will aim to document New (incident) stroke as assessed by the PedNIHSS |
3 years | |
Primary | The frequency, age specific prevalence and severity of Sickle Cell Vasculopathy manifested by a change in transcranial doppler (TCD) velocity by 15cm/sec or more over the 3-year study while on hydroxyurea treatment, compared to baseline assessment. | Baseline assessment will be completed for all study participants and over the 3-year study, scheduled outcome assessments will be performed at study months 18 and 36.These assessments will aim to document a change in TCD velocity by 15cm/sec or more. | 3 years | |
Primary | The frequency, age specific prevalence and severity of SCV manifested by New or worsening cognitive impairment, both quantitative and categorical over the 3-year study while on hydroxyurea treatment, compared to baseline assessments. | Baseline assessment will be completed for all study participants and over the 3-year study, scheduled outcome assessments will be performed at study months 18 and 36.These assessments will aim to document new or worsening cognitive impairment - both quantitative and categorical (by standardized criteria =-2 z-score) compared to established criteria | 3 years | |
Secondary | Stabilized or worsened structural changes on brain Magnetic Resonance Imaging(MRI) over the 3 years compared to baseline | Brain magnetic resonance will be performed on a subset of subjects at baseline and study month 36 only. Stabilized or worsened structural changes on brain Magnetic Resonance Imaging(MRI) over the 3 years compared to baseline will be assessed. | 3 years | |
Secondary | Stabilized or worsened structural changes on brain Magnetic Resonance Angiography(MRA) over the 3 years compared to baseline | Brain magnetic resonance angiography will be performed on a subset of subjects, at baseline and study month 36 only. Stabilized or worsened structural changes on brain Magnetic Resonance Angiography over the 3 years compared to baseline will be assessed. | 3 years |
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