Stroke Prevention in Young Adults With Sickle Cell Anemia

NCT04808778 | Active Not Recruiting DMC

• 1 other identifier: 190203
• Study Type: observational
• Target: 250
• Locations: 2 countries
• Sites: 2

Brief Summary

Sickle cell disease (SCD) is the most common genetic disease, affecting about 25 million people worldwide. Approximately 150,000 Nigerian children are born each year with sickle cell disease (SCD), making it the country with the largest burden of SCD in the world. Recent advancements in care for children with SCA have translated into improved survival of children in both high and low-resource settings. However, more complications of SCD are seen in those who survive to adulthood. Silent cerebral infarcts (SCI) and strokes are among the most devastating complications of SCD, affecting 40% and 10% of children, respectively. The overall goal of this study is to extend the Investigator's successful capacity-building effort in the assessment of neurological morbidity in children with SCD living in northern Nigeria (Kano) to young adults with SCD living in the same region. About 50% of all adults with SCD live in Nigeria. Despite the high prevalence of SCD in Africa, the neurological morbidity is not well characterized, limiting opportunities for primary and secondary stroke prevention strategies. At least 50% of young adults with sickle cell anemia (SCA), the most severe form of the disease, will have SCIs and an estimated 10% will have strokes, based on studies in high-resource settings. In high-resource settings, screening for abnormal transcranial Doppler (TCD) velocities in children with SCA, coupled with regular blood transfusion has resulted in a 92% reduction of relative risk for strokes. Despite this effective strategy, regular blood transfusion therapy does not seem sustainable in sub-Saharan Africa due to shortages and the risk of transfusion transmissible infections. Additionally, there is a lack of evidence-based stroke prevention strategies in young adults with SCA, either in the high-income or in low-resource settings. Based on the foregoing, the Investigators propose to determine the prevalence of neurological injury (overt stroke, transient ischemic attacks, and silent cerebral infarcts) in young adults at the transition age from 16-25 years. The Investigators will also, for the first time, assess conventional risk factors of stroke in the general population to determine whether a different prevention strategy is required to reduce the incidence of neurological injury in this high-risk population.

Conditions

Sickle Cell Disease; Sickle Cell Anemia; Stroke, Ischemic; Silent Stroke; Silent Cerebral Infarct; Stroke

Keywords

sickle cell anemia; stroke prevention; low-resource setting; silent cerebral infarct; northern Nigeria; young adults

Outcome Measures

Primary Outcomes (3)

• The prevalence of neurological morbidity in young adults with sickle cell anemia neurological examinations and MRA/MRI

  To estimate the prevalence of neurological morbidity including SCIs, strokes, and cerebral vasculopathy.

  1 year

• The prevalence of neurological morbidity in young adults with sickle cell anemia utilizing Transcranial Doppler (TCD) measurement

  Percentage of patients with abnormal TCD velocity (\> 200 cm/s)

  2 year

• Conventional risk factors of stroke

  We will also screen the participants for conventional risk factors of stroke (hypertension, smoking, diabetes, obesity, renal disease, cardiomyopathy, and atrial fibrillation).

  2 year

Secondary Outcomes (2)

• Long-term incidence of neurological morbidity in young adults with sickle cell anemia

  10 years

• Preliminary data for safety and feasibility of hydroxyurea therapy in young adults with sickle cell anemia

  2 years

Study Arms (2)

Participants with sickle cell anemia identified with neurological morbidity

1. Successful completion of screening procedures inclusive of 1.) Cerebral blood flow velocity greater than or equal to 180 cm/sec measured twice or 2.) At least one measurement greater than or equal to 220 cm/sec in the middle cerebral artery or 3.) Two TCD measurements above 180 cm/sec within a three-month interval; 2. MRI showing cerebral infarcts with or without (based on Silent Cerebral Infarct Trial (SIT) criteria) neurological deficits on standard neurological examination; 3. Informed consent from a participant (\> 18 years) or parent/legal guardian for participants (\< 18 years) and assent of the participant completed; 4. Acceptance of hydroxyurea therapy for one year as standard care. After one year of therapy, the participant will have the option to continue therapy with follow-up visits to monitor adherence to therapy with his or her care provider.

Drug: Hydroxyurea therapy per standard care

Participants with sickle cell anemia identified to be without neurological morbidity

1. Successful completion of screening procedures inclusive of cerebral blood flow velocity less than or equal to 170 cm/sec in the middle cerebral artery; 2. Normal MRI and MRA; 3. No focal neurological deficit on standard neurological examination; 4. Informed consent from a participant (\> 18 years), or parent/legal guardian for participants (\< 18 years) and assent from the participant; 5. Agreement to be followed for at least one year in the study.

Interventions

Hydroxyurea therapy per standard care DRUG

Moderate-dose of 20mg/kg/day

Also known as: Hydrea

Participants with sickle cell anemia identified with neurological morbidity

Eligibility Criteria

• Age: 16 Years - 26 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

A total of 250 participants with sickle cell anemia between 16 through 25 years of age living in northern Nigeria receiving care at the Aminu Kano Teaching Hospital in Kano Nigeria.

You may qualify if:

• Patients with hemoglobin S-S or Sβ0 thalassemia confirmed by hemoglobin electrophoresis or High-Performance Liquid Chromatography (HPLC);
• Participant is 16 through 25 years of age;
• Informed consent from participants above 18 years, and informed consent from a parent or legal guardian and assent of participants aged \< 18 years (assessment can take place up until the 26th birthday);
• Participant resides within an hour driving distance from the medical center to facilitate weekly phone calls between the scheduled monthly clinic visits;
• Participant is willing to be enrolled and followed for the duration of the study.

You may not qualify if:

• Young adults with co-morbidities that may have an impact on neurological status, such as epilepsy;
• Young adults enrolled in clinical trials upon entry;
• Participants with an implanted defibrillator or certain other implanted electronic or metallic devices contraindicated for MRI;
• Young adults with known HIV diagnosis;
• Any other condition or chronic illness, which in the opinion of the site's Principal Investigator (PI) makes participation ill-advised or unsafe.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Aminu Kano Teaching Hospital: collaborator

Study Sites (2)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-9000, United States

Location

Aminu Kano Teaching Hospital

Kano, Nigeria

Location

MeSH Terms

Conditions

Anemia, Sickle Cell; Ischemic Stroke; Stroke

Interventions

Hydroxyurea

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

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• 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, Vice Chair for Clinical and Translational Research

Study Record Dates

• First Submitted: March 17, 2021
• First Posted: March 22, 2021
• Study Start: May 17, 2021
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: September 5, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); NG (1)