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Epidemiology of Silent and Overt Strokes in Sickle Cell Disease (ESCD)

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ClinicalTrials.gov Identifier: NCT03376893
Recruitment Status : Recruiting
First Posted : December 19, 2017
Last Update Posted : February 25, 2019
Sponsor:
Collaborators:
Washington University School of Medicine
University of Alabama at Birmingham
Information provided by (Responsible Party):
Michael DeBaun, Vanderbilt University Medical Center

Brief Summary:
Sickle Cell Disease (SCD) is a rare disease occurring in an estimated 100,000 children and adults, often poor and underserved, in the United States. Silent strokes 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 (RCT) 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. In three adult sickle cell disease 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.

Condition or disease
Anemia, Sickle Cell Sickle Cell Disease Stroke Sickle Cell Thalassemia Sickle Cell-Beta0-Thalassemia

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Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Epidemiology of Silent and Overt Strokes in Adults With Sickle Cell Disease: a Prospective Cohort Study
Actual Study Start Date : June 2, 2017
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : July 2023


Group/Cohort
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.



Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. Cognitive morbidity in those with silent or overt stroke [ Time Frame: Study enrollment ]
    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.

  2. Cognitive morbidity in those with silent or overt stroke [ Time Frame: Every 12 to 18 months after enrollment ]
    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.

  3. Cognitive morbidity in those with silent or overt stroke [ Time Frame: At study exit (at least 3.5 years after enrollment) ]
    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.

  4. Adjudication of overt stroke in those with reported history of overt stroke and on transfusion 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 an overt stroke has occurred.

  5. Adjudication of new strokes in those with history of overt stroke and on transfusion 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.

  6. 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) ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Participants will be patient volunteers from the sickle cell disease clinics of participating study sites.
Criteria

Inclusion Criteria:

  1. Participants with sickle cell disease on hemoglobin analysis and/or other confirmatory documentation of phenotype
  2. Patients ≥ 18 years of age
  3. Patients followed regularly (at least two visits per year) in the hematology clinics
  4. Patients who have demonstrated adherence with follow-up visits for ≥ 3 years
  5. 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.
  6. Willingness to comply with study protocol, routine clinic visits

Exclusion criteria:

  1. Participants judged to be non-compliant by the hematologist based on previous experience in terms of clinic appointments and following advice
  2. Participants with contraindications to MRI, including individuals with MRI-incompatible foreign metal objects

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03376893


Contacts
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Contact: Casey M Babb, MS 615-875-8794 casey.m.babb@vanderbilt.edu
Contact: Brittany V Covert, MPH 615-343-4855 brittany.covert@vanderbilt.edu

Locations
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United States, Alabama
University of Alabama at Birmingham Not yet recruiting
Birmingham, Alabama, United States, 35233
Contact: Jeffrey Lebensburger, DO    205-638-9285    jlebensburger@peds.uab.edu   
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Allison A King, MD    314-454-4291    king_a@wustl.edu   
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Casey M Babb, MS    615-875-8794    casey.m.babb@vumc.org   
Sponsors and Collaborators
Vanderbilt University Medical Center
Washington University School of Medicine
University of Alabama at Birmingham
Investigators
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Principal Investigator: Michael R DeBaun, MD, MPH Vanderbilt University Medical Center
  Study Documents (Full-Text)

Documents provided by Michael DeBaun, Vanderbilt University Medical Center:
Study Protocol  [PDF] November 21, 2016


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Responsible Party: Michael DeBaun, Professor of Pediatrics and Medicine, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT03376893     History of Changes
Other Study ID Numbers: 161434
First Posted: December 19, 2017    Key Record Dates
Last Update Posted: February 25, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Stroke
Anemia, Sickle Cell
Thalassemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn