Epidemiology of Silent and Overt Strokes in Sickle Cell Disease

NCT03376893 | Active Not Recruiting

• 1 other identifier: 161434
• Study Type: observational
• Target: 102
• Locations: 1 country
• Sites: 4

Brief 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. 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.

Conditions

Stroke; Sickle Cell Thalassemia; Sickle Cell-Beta0-Thalassemia; Anemia, Sickle Cell; Sickle Cell Disease

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  At study exit (at least 3.5 years after enrollment)

Secondary Outcomes (6)

• Cognitive morbidity in those with silent or overt stroke

  Study enrollment

• Cognitive morbidity in those with silent or overt stroke

  Every 12 to 18 months after enrollment

• Cognitive morbidity in those with silent or overt stroke

  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

  Study enrollment

• Adjudication of new strokes in those with history of overt stroke and on transfusion therapy

  Every 12 to 18 months after enrollment

Study Arms (3)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be patient volunteers from the sickle cell disease clinics of participating study sites.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Washington University School of Medicine: collaborator
• University of Alabama at Birmingham: collaborator

Study Sites (4)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-9000, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell; Stroke

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Lori C. Jordan, PhD, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Michael R DeBaun, MD, MPH

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics and Medicine

Study Record Dates

• First Submitted: December 8, 2017
• First Posted: December 19, 2017
• Study Start: June 2, 2017
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)