Sickle Cell Anemia in ChildrenPhase 2NCT03948867
Stroke Prevention With Hydroxyurea Enabled Through Research and Education (SPHERE)
A Phase 2 study testing Hydroxyurea, Elevated Arm TCD Examination and Normal Arm TCD Examination in people with Sickle Cell Anemia in Children, run by Children's Hospital Medical Center, Cincinnati at 2 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 2 to 16 years
- Conditions the study is for
- Sickle Cell Anemia in Children
- What is being tested?
- Hydroxyurea, Elevated Arm TCD Examination and Normal Arm TCD Examination
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 202 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 24 Apr 2019to 31 Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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)
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- Known medical condition making participation ill-advised.
- Known allergic reactions to components of hydroxyurea.
- Previous history of stroke.
- Currently pregnant or lactating.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: Stroke Prevention With Hydroxyurea Enabled Through Research and Education (SPHERE): A Prospective Trial to Reduce Primary Stroke in Children With Sickle Cell Anaemia
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.
Read the detailed description
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.
- Conditions
- Sickle Cell Anemia in Children
- Being tested
- Hydroxyurea, Elevated Arm TCD Examination, Normal Arm TCD Examination
- Keywords
- Sickle Celll Anemia, Transcranial Doppler, Tanzania, Hydroxyurea, Stroke
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydroxyureaDrug
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 ExaminationDiagnostic 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 ExaminationDiagnostic 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).
| Study group | Role | What they receive |
|---|---|---|
| Elevated Initial Screening TCD | Experimental | Those who have an elevated initial screening TCD (either conditional or abnormal TAMV) and will be a treatment cohort that receives open-label hydroxyurea therapy as per the dosing and administration schedule. Receives: Drug: Hydroxyurea; Diagnostic Test: Elevated Arm TCD Examination |
| Normal Initial Screening TCD | Experimental | Those who are found to have a normal TCD at enrolment are a part of the observation/control cohort and will undergo repeat TCD every 12 months after enrolment. If the TCD at 12 months has changed to an elevated velocity (conditional or abnormal), the study participant will be reassigned to the elevated initial screening TCD arm and can begin study treatment (hydroxyurea), but will not be included in the primary endpoint analysis. Receives: Diagnostic Test: Normal Arm TCD Examination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of Elevated TCD
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
Measured: Baseline
Change in Primary Stroke Risk
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.
Measured: Up to 12 Months at Month 12
Secondary outcomes (6)
Laboratory and Clinical Correlates
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
Measured: Up to 24 Months
Change in Hemoglobin Concentration
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.
Measured: 6 Months
Effect of Splenomegaly and Malaria Infections
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.
Measured: Up to 24 Months
Prevalence of Co-inherited G6PD and Alpha Thalassemia
DNA will be collected at baseline to determine the prevalence of co-inherited hematologic diseases such as G6PD and alpha thalassemia.
Measured: One time at Baseline
Hydroxyurea Area Under the Curve (AUC)
For those receiving hydroxyurea, the AUC will be assessed after the patient has reached MTD.
Measured: One time at 24 Months (Study Exit)
Single Nucleotide Polymorphisms Associated with Change in Percent Hemoglobin F on Hydroxyurea
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.
Measured: One Time at 24 Months (Study Exit)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2019
- Study start24 Apr 2019
- Primary completion5 Sep 2022
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell Anemia in ChildrenStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The cohort will be divided into two arms based on the initial screening TCD result: 1) those who have a normal initial screening TCD and will be an observation/control cohort; and 2) those who have an elevated initial screening TCD (either conditional or abnormal TAMV) and will be a treatment cohort that receives open-label hydroxyurea therapy as per the dosing and administration schedule
- Masking
- None (open label)
- Enrolment
- 202 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Bugando Medical Centre, The American Society of Hematology
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03948867
- Sponsor's protocol ID
- SPHERE
- Status last verified
- Oct 2026
- First submitted
- 8 Feb 2019
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Ambrose EE, Latham TS, Songoro P, Charles M, Lane AC, Stuber SE, Makubi AN, Ware RE, Smart LR. Hydroxyurea with dose escalation for primary stroke risk reduction in children with sickle cell anaemia in Tanzania (SPHERE): an open-label, phase 2 trial. Lancet Haematol. 2023 Apr;10(4):e261-e271. doi: 10.1016/S2352-3026(22)00405-7. Epub 2023 Mar 1.
PubMed 36870358
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stroke Prevention With Hydroxyurea Enabled Through Research and Education (SPHERE): A Prospective Trial to Reduce Primary Stroke in Children With Sickle Cell Anaemia
- ClinicalTrials.gov ID
- NCT03948867
- Acronym / sponsor ID
- SPHERE
- Conditions
- Sickle Cell Anemia in Children
- Keywords
- Sickle Celll Anemia, Transcranial Doppler, Tanzania, Hydroxyurea, Stroke
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 202 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Bugando Medical Centre, The American Society of Hematology
- Study start
- 24 Apr 2019 (actual)
- Primary completion
- 5 Sep 2022 (actual)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 14 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The cohort will be divided into two arms based on the initial screening TCD result: 1) those who have a normal initial screening TCD and will be an observation/control cohort; and 2) those who have an elevated initial screening TCD (either conditional or abnormal TAMV) and will be a treatment cohort that receives open-label hydroxyurea therapy as per the dosing and administration schedule
| Arm | Type | Receives |
|---|---|---|
| Elevated Initial Screening TCD | Experimental | Drug: Hydroxyurea, Diagnostic Test: Elevated Arm TCD ExaminationThose who have an elevated initial screening TCD (either conditional or abnormal TAMV) and will be a treatment cohort that receives open-label hydroxyurea therapy as per the dosing and administration schedule. |
| Normal Initial Screening TCD | Experimental | Diagnostic Test: Normal Arm TCD ExaminationThose who are found to have a normal TCD at enrolment are a part of the observation/control cohort and will undergo repeat TCD every 12 months after enrolment. If the TCD at 12 months has changed to an elevated velocity (conditional or abnormal), the study participant will be reassigned to the elevated initial screening TCD arm and can begin study treatment (hydroxyurea), but will not be included in the primary endpoint analysis. |
Who may qualify
- Ages
- 2 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (10 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxyureaHydroxyurea 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). | Drug | Elevated Initial Screening TCD |
| Elevated Arm TCD ExaminationTCD 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. | Diagnostic test | Elevated Initial Screening TCD |
| Normal Arm TCD ExaminationTCD 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). | Diagnostic test | Normal Initial Screening TCD |
Primary outcome
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
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.
6 secondary outcomes
Laboratory and Clinical Correlates
Time frame: Up to 24 Months
Change in Hemoglobin Concentration
Time frame: 6 Months
Effect of Splenomegaly and Malaria Infections
Time frame: Up to 24 Months
Prevalence of Co-inherited G6PD and Alpha Thalassemia
Time frame: One time at Baseline
Hydroxyurea Area Under the Curve (AUC)
Time frame: One time at 24 Months (Study Exit)
Single Nucleotide Polymorphisms Associated with Change in Percent Hemoglobin F on Hydroxyurea
Time frame: One Time at 24 Months (Study Exit)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
- Derived from this study: PubMed 36870358Ambrose EE, Latham TS, Songoro P, Charles M, Lane AC, Stuber SE, Makubi AN, Ware RE, Smart LR. Hydroxyurea with dose escalation for primary stroke risk reduction in children with sickle cell anaemia in Tanzania (SPHERE): an open-label, phase 2 trial. Lancet Haematol. 2023 Apr;10(4):e261-e271. doi: 10.1016/S2352-3026(22)00405-7. Epub 2023 Mar 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hydroxyurea, Elevated Arm TCD Examination and Normal Arm TCD Examination in people with Sickle Cell Anemia in Children, run by Children's Hospital Medical Center, Cincinnati at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of Elevated TCD (time frame: Baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03948867, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.