Skip to main content
OpenTrials
Enrolling by Invitation

NCT Number: NCT03948867

Stroke Prevention With Hydroxyurea Enabled Through Research and Education (SPHERE)

This study will 1) Evaluate the prevalence of elevated (conditional or abnormal) transcranial Doppler (TCD) velocities in a cross-sectional analysis of children with Sickle Cell Anemia (SCA) living in Tanzania; 2) Obtain longitudinal data on TCD velocities in this population; and 3) Measure the effects of hydroxyurea therapy on TCD velocities and associated primary stroke risk.

Enrolling by Invitation

Interested in participating?

Request Info

Key information

Conditions

Sickle Cell Anemia in Children Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Nervous System Diseases Stroke Vascular Diseases

Age range

2 year–16 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Bugando Medical Centre, Mwanza, Tanzania

Loading trial locations.

About this study

Stroke Prevention with Hydroxyurea Enabled through Research and Education (SPHERE) is a single-center prospective phase 2 pilot study. It will enroll a convenience sample of children with SCA, obtain cross-sectional baseline data at enrolment, and follow them as a prospective cohort for a period of 24 months. The cohort will be divided into two arms based on the initial screening TCD result: 1) those who have a normal (less than 170 cm/sec time averaged mean velocity (TAMV)) initial screening TCD and will be an observation/control cohort; and 2) those who have an elevated initial screening TCD (either conditional (170-199 cm/sec) or abnormal (greater than or equal to 200 cm/sec) TAMV) and will be a treatment cohort that receives open-label hydroxyurea therapy as per the dosing and administration schedule. Those who are found to have a normal TCD at enrolment and are part of the observation/control cohort will undergo repeat TCD 12 months after enrolment. If the TCD at 12 months has changed to an elevated velocity (conditional or abnormal), the study participant can begin study treatment, but will not be included in the primary endpoint analysis. The primary hypothesis is after 12 months of hydroxyurea therapy, children with conditional TCD velocities will achieve a mean decrease of >15cm/sec from their baseline TCD TAMV.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Willingness to sign informed consent
  • Willingness to follow all study procedures
  • Available for study visits for the duration of the study and no plans to move away from study center.
  • Confirmed diagnosis of Sickle Cell Anemia (SCA) by haemoglobin electrophoresis.
  • Able to take oral medication and follow hydroxyurea treatment schedule.

Exclusion criteria

There are no permanent exclusion criteria for participants to enroll in the screening TCD portion of SPHERE. Temporary, time-limited exclusion criteria for the screening TCD portion include the following:

  • Febrile illness within the past two weeks. (Temporary Exclusion)
  • Hospitalized within the past two weeks. (Temporary Exclusion)
  • Transfusion within the past two weeks. (Temporary Exclusion)

Patients who enroll in the screening portion, have a conditional or abnormal TCD, and are eligible to start hydroxyurea will be excluded from receiving study treatment if they meet any of the following criteria:

  • Abnormal pre-enrolment laboratory values (Temporary Exclusion)
  • Known medical condition making participation ill-advised.
  • Known allergic reactions to components of hydroxyurea.
  • Previous history of stroke.
  • Currently pregnant or lactating.

Treatment and study plan

Hydroxyurea

Drug

Hydroxyurea treatment will be provided to reduce stroke risk. Hydroxyurea treatment will be started at a fixed dose of 20.0 ± 5.0 mg/kg/day, followed by escalation to maximum tolerated dose (MTD).

Elevated Arm TCD Examination

Diagnostic Test

TCD examination on children with SCA between ages 2 and 16 years of age will be completed to evaluate their risk of stroke.

For children with elevated velocities at initial screening or at 1 Year who receive hydroxyurea therapy, TCD examinations will occur every 6 ± 2 months.

Normal Arm TCD Examination

Diagnostic Test

TCD examination on children with SCA between ages 2 and 16 years of age will be completed to evaluate their risk of stroke. TCD examination for all participants will occur at initial screening, at Year 1 (12 ± 3 months), and Year 2 (24 ± 3 months). Children with normal TCD velocities at initial screening will undergo repeat TCD 12 months after enrolment. If the TCD at 12 months has changed to an elevated velocity (conditional or abnormal), the child can begin study treatment (Hydroxyurea).

Primary outcomes

  1. Prevalence of Elevated TCD

    Time frame: Baseline

    Determine the prevalence of elevated (conditional or abnormal) transcranial Doppler (TCD) velocities in a cross-sectional analysis of children with Sickle Cell Anemia (SCA) living in Tanzania

  2. Change in Primary Stroke Risk

    Time frame: Up to 12 Months at Month 12

    Transcranial Doppler ultrasound (TCD) will be used to measure the change in the TAMV of arterial blood flow in the 4 major intracranial arteries bilaterally from study enrollment to 12 months after study enrollment.

Secondary outcomes

  1. Laboratory and Clinical Correlates

    Time frame: Up to 24 Months

    Identify laboratory and clinical correlates of elevated TCD velocities such as age, haemoglobin concentration, foetal haemoglobin, oxygen saturation, splenomegaly, history of acute chest syndrome, and previous malaria infection

  2. Change in Hemoglobin Concentration

    Time frame: 6 Months

    For those receiving hydroxyurea, the change in hemoglobin between baseline hemoglobin and follow up hemoglobin when a participant has reached maximum tolerated dose of hydroxyurea.

  3. Effect of Splenomegaly and Malaria Infections

    Time frame: Up to 24 Months

    Incidence of splenomegaly and malaria infection with rapid or laboratory malaria testing will be performed for any child presenting with fever. Incidence will be reported in the number of cases per 100 patient years. Abdominal ultrasound with splenic volume will be performed annually for all study participants. Quantify the degree of hypersplenism or autoinfarction and any association with malaria complications of SCA will be analyzed.

  4. Prevalence of Co-inherited G6PD and Alpha Thalassemia

    Time frame: One time at Baseline

    DNA will be collected at baseline to determine the prevalence of co-inherited hematologic diseases such as G6PD and alpha thalassemia.

  5. Hydroxyurea Area Under the Curve (AUC)

    Time frame: One time at 24 Months (Study Exit)

    For those receiving hydroxyurea, the AUC will be assessed after the patient has reached MTD.

  6. Single Nucleotide Polymorphisms Associated with Change in Percent Hemoglobin F on Hydroxyurea

    Time frame: One Time at 24 Months (Study Exit)

    For those receiving hydroxyurea, we will identify single nucleotide polymorphisms that are associated with a greater change in hemoglobin F percent in response to hydroyxurea therapy.

Sponsors and collaborators

Lead sponsor

Children's Hospital Medical Center, Cincinnati

Other

Collaborators

  • Bugando Medical Centre
  • The American Society of Hematology

Registry information

Official study title

Stroke Prevention With Hydroxyurea Enabled Through Research and Education (SPHERE): A Prospective Trial to Reduce Primary Stroke in Children With Sickle Cell Anaemia

Important dates

Study start
2019
Primary completion
2026
Study completion
2026
First posted
May 14, 2019
Registry last updated
Jul 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.