Anemia, Sickle CellESCDNCT03376893
Epidemiology of Silent and Overt Strokes in Sickle Cell Disease
An observational study of Anemia, Sickle Cell and Sickle Cell Disease, run by Vanderbilt University Medical Center at 4 sites in United States.
Trial summary
Sickle Cell Disease (SCD) is a rare disease occurring in an estimated 100,000 individuals, often poor and underserved, in the US. Silent and overt strokes contribute significantly to morbidity in adults with SCD, resulting in functional impairment, challenges with school and job performance, and premature death. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anemia, Sickle Cell, Sickle Cell Disease, Stroke
- How many people
- 102 participants
- Where
- 4 sitesUnited States
- Study dates
- 2 Jun 2017to 31 Dec 2026
- Phase
- Observational
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Participants will be patient volunteers from the sickle cell disease clinics of participating study sites.
Who may be able to join
- Participants with sickle cell disease on hemoglobin analysis and/or other confirmatory documentation of phenotype
- Patients ≥ 18 years of age
- Patients followed regularly (at least two visits per year) in the hematology clinics
- Patients who have demonstrated adherence with follow-up visits for ≥ 3 years
- Patients willing to be followed prospectively for a minimum of 3.5 years and agree to a standard care exit MRI/MRA of the brain, as well as MRI/MRA every 12 to 18 months or participation in VUMC AHA trial with Dr. Jordan as PI. These are adults with SCA aged 18-40 years at study entry, enrolled with any infarct status (none, SCI or overt stroke) and followed prospectively.
- Willingness to comply with study protocol, routine clinic visits
Who cannot join
- Participants judged to be non-compliant by the hematologist based on previous experience in terms of clinic appointments and following advice
- Participants with contraindications to MRI, including individuals with MRI-incompatible foreign metal objects
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Vanderbilt University Medical Center
Nashville, Tennessee, 37232-9000
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: The Epidemiology of Silent and Overt Strokes in Adults With Sickle Cell Disease: a Prospective Cohort Study
Sickle Cell Disease (SCD) is a rare disease occurring in an estimated 100,000 individuals, often poor and underserved, in the US. Silent and overt strokes contribute significantly to morbidity in adults with SCD, resulting in functional impairment, challenges with school and job performance, and premature death. Five NIH-funded randomized controlled trials have identified therapies to prevent silent and overt strokes in children with SCD, including monthly blood transfusion therapy (for preventing initial and recurrent strokes) and hydroxyurea (for preventing initial strokes). Despite the observation that at least 99% of children with SCD in high-income countries reach adulthood, and approximately 60% of adults will experience one or more strokes (~50% with silent strokes and ~10% with overt strokes), no stroke trials have established therapeutic approaches for adults with SCD. For adults with SCD, inadequate evidence-based guidelines exist for secondary stroke prevention strategies. Applying stroke prevention strategies in children may not be effective for stroke prevention in adults with SCD, particularly given the high rate of co-morbidities. Identifying subgroups of adults with SCD and higher incidence coupled with the contribution of established stroke risk factors in the general population (smoking, diabetes, obesity, renal disease) will provide the requisite data required for the first-ever phase III clinical trials focused on secondary stroke prevention in adults.
Read the detailed description
In three adult SCD centers, we will conduct a prospective cohort study to test the primary hypothesis that the incidence of infarct recurrence (stroke or silent stroke) or new strokes in adults with silent strokes treated with hydroxyurea will be greater than in those without strokes treated with hydroxyurea. We will test two secondary hypotheses: 1) adults with SCD and silent strokes have cognitive morbidity when compared to adults with SCD without silent strokes, and 2) adults with SCD and strokes receiving regular blood transfusion will have a higher incidence of infarct recurrence than those with SCD without strokes. The aims include Aim 1: Compare the incidence of new overt and silent strokes in adults with SCD and silent strokes to a comparison group of adults without silent strokes or overt strokes. Aim 2: Compare the cognitive morbidity of those with silent strokes and overt strokes to those without strokes. Aim 3: Compare the incidence of new overt and silent stroke in adults with SCD and overt strokes receiving transfusion to adults with SCD without silent or overt strokes treated with hydroxyurea. All clinical information and neuroimaging will be centrally adjudicated with masked and experienced neurology and neuroradiology committees. Data generated after completion of this proposal are critical for developing the first-ever phase III trials for secondary stroke prevention therapies in adults with SCD.
- Conditions
- Anemia, Sickle Cell, Sickle Cell Disease, Stroke, Sickle Cell Thalassemia, Sickle Cell-Beta0-Thalassemia
- Medical subject headings
- Anemia, Sickle Cell, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| SCA with overt stroke | Participants have sickle cell disease and a history of overt stroke. | |
| SCA with silent stroke | Participants have sickle cell disease and a history of silent stroke. | |
| SCA with no stroke | Participants have sickle cell disease and no history of stroke. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adjudication of silent stroke in those with reported history of silent stroke and hydroxyurea therapy
Based on results of an MRI exam and a neurological exam, performed by a physician, the Neuroradiology Committee and the Neurology Committee will come to consensus on whether a silent stroke has occurred. Radiologically, silent stroke will be defined as a FLAIR T2W hyperintensity greater than 3 mm, visible in two planes. Neurologically, a silent stroke has no neurological sequelae.
Measured: Study enrollment
Adjudication of new strokes in those with history of silent stroke and on hydroxyurea therapy
Based on results of an MRI exam and a neurological exam, performed by a physician, the Neuroradiology Committee and the Neurology Committee will come to consensus on whether a NEW stroke has occurred since the last exams, and if so, whether it is a silent stroke or overt stroke. Radiologically, silent stroke will be defined as a FLAIR T2W hyperintensity greater than 3 mm, visible in two planes. Neurologically, a silent stroke has no neurological sequelae.
Measured: Every 12 to 18 months after enrollment
Adjudication of new strokes in those with history of silent stroke and on hydroxyurea therapy
Based on results of an MRI exam and a neurological exam, performed by a physician, the Neuroradiology Committee and the Neurology Committee will come to consensus on whether a NEW stroke has occurred since the last exams, and if so, whether it is a silent stroke or overt stroke. Radiologically, silent stroke will be defined as a FLAIR T2W hyperintensity greater than 3 mm, visible in two planes. Neurologically, a silent stroke has no neurological sequelae.
Measured: At study exit (at least 3.5 years after enrollment)
Secondary outcomes (6)
Cognitive morbidity in those with silent or overt stroke
All participants will complete the NIH Toolbox CB. The NIH Toolbox CB allows for the evaluation of several cognitive constructs and yields individual measure scores as well as a composite score. This measure will serve as a baseline for all participants.
Measured: Study enrollment
Cognitive morbidity in those with silent or overt stroke
Participants will complete the NIH Toolbox CB. The NIH Toolbox CB allows for the evaluation of several cognitive constructs and yields individual measure scores as well as a composite score. Results will be compared to the previous measurement(s) to determine if change has occurred.
Measured: Every 12 to 18 months after enrollment
Cognitive morbidity in those with silent or overt stroke
Participants will complete the NIH Toolbox CB. The NIH Toolbox CB allows for the evaluation of several cognitive constructs and yields individual measure scores as well as a composite score. Results will be compared to the previous measurement(s) to determine if change has occurred.
Measured: At study exit (at least 3.5 years after enrollment)
Adjudication of overt stroke in those with reported history of overt stroke and on transfusion therapy
Based on results of an MRI exam and a neurological exam, performed by a physician, the Neuroradiology Committee and the Neurology Committee will come to consensus on whether an overt stroke has occurred.
Measured: Study enrollment
Adjudication of new strokes in those with history of overt stroke and on transfusion therapy
Based on results of an MRI exam and a neurological exam, performed by a physician, the Neuroradiology Committee and the Neurology Committee will come to consensus on whether a NEW stroke has occurred since the last exams, and if so, whether it is a silent stroke or overt stroke. Radiologically, silent stroke will be defined as a FLAIR T2W hyperintensity greater than 3 mm, visible in two planes. Neurologically, a silent stroke has no neurological sequelae.
Measured: Every 12 to 18 months after enrollment
Adjudication of new strokes in those with history of overt stroke and on transfusion therapy
Based on results of an MRI exam and a neurological exam, performed by a physician, the Neuroradiology Committee and the Neurology Committee will come to consensus on whether a NEW stroke has occurred since the last exams, and if so, whether it is a silent stroke or overt stroke. Radiologically, silent stroke will be defined as a FLAIR T2W hyperintensity greater than 3 mm, visible in two planes. Neurologically, a silent stroke has no neurological sequelae.
Measured: At study exit (at least 3.5 years after enrollment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2017
- Study start2 Jun 2017
- Primary completion31 Dec 2025
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anemia, Sickle CellStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael DeBaun, Vanderbilt University Medical Center
- Investigators
- Lori C. Jordan, PhD, MD, Principal investigator, Vanderbilt University Medical CenterMichael R DeBaun, MD, MPH, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03376893
- Sponsor's protocol ID
- 161434
- Acronym
- ESCD
- Status last verified
- Feb 2026
- First submitted
- 8 Dec 2017
- Last updated
- 13 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Epidemiology of Silent and Overt Strokes in Adults With Sickle Cell Disease: a Prospective Cohort Study
- ClinicalTrials.gov ID
- NCT03376893
- Acronym / sponsor ID
- ESCD / 161434
- Conditions
- Anemia, Sickle Cell, Sickle Cell Disease, Stroke, Sickle Cell Thalassemia, Sickle Cell-Beta0-Thalassemia
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- Washington University School of Medicine, University of Alabama at Birmingham
- Study start
- 2 Jun 2017 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 19 Dec 2017 (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.
Sickle Cell Disease (SCD) is a rare disease occurring in an estimated 100,000 individuals, often poor and underserved, in the US. Silent and overt strokes contribute significantly to morbidity in adults with SCD, resulting in functional impairment, challenges with school and job performance, and premature death. Five NIH-funded randomized controlled trials have identified therapies to prevent silent and overt strokes in children with SCD, including monthly blood transfusion therapy (for preventing initial and recurrent strokes) and hydroxyurea (for preventing initial strokes). Despite the observation that at least 99% of children with SCD in high-income countries reach adulthood, and approximately 60% of adults will experience one or more strokes (~50% with silent strokes and ~10% with overt strokes), no stroke trials have established therapeutic approaches for adults with SCD. For adults with SCD, inadequate evidence-based guidelines exist for secondary stroke prevention strategies. Applying stroke prevention strategies in children may not be effective for stroke prevention in adults with SCD, particularly given the high rate of co-morbidities. Identifying subgroups of adults with SCD and higher incidence coupled with the contribution of established stroke risk factors in the general population (smoking, diabetes, obesity, renal disease) will provide the requisite data required for the first-ever phase III clinical trials focused on secondary stroke prevention in adults.
Detailed description
In three adult SCD centers, we will conduct a prospective cohort study to test the primary hypothesis that the incidence of infarct recurrence (stroke or silent stroke) or new strokes in adults with silent strokes treated with hydroxyurea will be greater than in those without strokes treated with hydroxyurea. We will test two secondary hypotheses: 1) adults with SCD and silent strokes have cognitive morbidity when compared to adults with SCD without silent strokes, and 2) adults with SCD and strokes receiving regular blood transfusion will have a higher incidence of infarct recurrence than those with SCD without strokes. The aims include Aim 1: Compare the incidence of new overt and silent strokes in adults with SCD and silent strokes to a comparison group of adults without silent strokes or overt strokes. Aim 2: Compare the cognitive morbidity of those with silent strokes and overt strokes to those without strokes. Aim 3: Compare the incidence of new overt and silent stroke in adults with SCD and overt strokes receiving transfusion to adults with SCD without silent or overt strokes treated with hydroxyurea. All clinical information and neuroimaging will be centrally adjudicated with masked and experienced neurology and neuroradiology committees. Data generated after completion of this proposal are critical for developing the first-ever phase III trials for secondary stroke prevention therapies in adults with SCD.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| SCA with overt stroke | – | –Participants have sickle cell disease and a history of overt stroke. |
| SCA with silent stroke | – | –Participants have sickle cell disease and a history of silent stroke. |
| SCA with no stroke | – | –Participants have sickle cell disease and no history of stroke. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Participants will be patient volunteers from the sickle cell disease clinics of participating study sites.
Key inclusion criteria (6 listed)
- Participants with sickle cell disease on hemoglobin analysis and/or other confirmatory documentation of phenotype
- Patients ≥ 18 years of age
- Patients followed regularly (at least two visits per year) in the hematology clinics
- Patients who have demonstrated adherence with follow-up visits for ≥ 3 years
- Patients willing to be followed prospectively for a minimum of 3.5 years and agree to a standard care exit MRI/MRA of the brain, as well as MRI/MRA every 12 to 18 months or participation in VUMC AHA trial with Dr. Jordan as PI. These are adults with SCA aged 18-40 years at study entry, enrolled with any infarct status (none, SCI or overt stroke) and followed prospectively.
Key exclusion criteria (2 listed)
- Participants judged to be non-compliant by the hematologist based on previous experience in terms of clinic appointments and following advice
- Participants with contraindications to MRI, including individuals with MRI-incompatible foreign metal objects
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Adjudication of silent stroke in those with reported history of silent stroke and hydroxyurea therapy
Time frame: Study enrollment
Based on results of an MRI exam and a neurological exam, performed by a physician, the Neuroradiology Committee and the Neurology Committee will come to consensus on whether a silent stroke has occurred. Radiologically, silent stroke will be defined as a FLAIR T2W hyperintensity greater than 3 mm, visible in two planes. Neurologically, a silent stroke has no neurological sequelae.
Adjudication of new strokes in those with history of silent stroke and on hydroxyurea therapy
Time frame: Every 12 to 18 months after enrollment
Based on results of an MRI exam and a neurological exam, performed by a physician, the Neuroradiology Committee and the Neurology Committee will come to consensus on whether a NEW stroke has occurred since the last exams, and if so, whether it is a silent stroke or overt stroke. Radiologically, silent stroke will be defined as a FLAIR T2W hyperintensity greater than 3 mm, visible in two planes. Neurologically, a silent stroke has no neurological sequelae.
Adjudication of new strokes in those with history of silent stroke and on hydroxyurea therapy
Time frame: At study exit (at least 3.5 years after enrollment)
Based on results of an MRI exam and a neurological exam, performed by a physician, the Neuroradiology Committee and the Neurology Committee will come to consensus on whether a NEW stroke has occurred since the last exams, and if so, whether it is a silent stroke or overt stroke. Radiologically, silent stroke will be defined as a FLAIR T2W hyperintensity greater than 3 mm, visible in two planes. Neurologically, a silent stroke has no neurological sequelae.
6 secondary outcomes
Cognitive morbidity in those with silent or overt stroke
Time frame: Study enrollment
Cognitive morbidity in those with silent or overt stroke
Time frame: Every 12 to 18 months after enrollment
Cognitive morbidity in those with silent or overt stroke
Time frame: At study exit (at least 3.5 years after enrollment)
Adjudication of overt stroke in those with reported history of overt stroke and on transfusion therapy
Time frame: Study enrollment
Adjudication of new strokes in those with history of overt stroke and on transfusion therapy
Time frame: Every 12 to 18 months after enrollment
Adjudication of new strokes in those with history of overt stroke and on transfusion therapy
Time frame: At study exit (at least 3.5 years after enrollment)
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 13 Feb 2026.
- Individual participant dataSharing planned: No
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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.
Lori C. Jordan, PhD, MD principal investigator
Vanderbilt University Medical Center
Michael R DeBaun, MD, MPH principal investigator
Vanderbilt University Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Anemia, Sickle Cell and Sickle Cell Disease, run by Vanderbilt University Medical Center at 4 sites in United States.
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 6 inclusion and 2 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 13 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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.
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?
Adjudication of silent stroke in those with reported history of silent stroke and hydroxyurea therapy (time frame: Study enrollment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Feb 2026.