Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT04808778 |
Other study ID # |
190203 |
Secondary ID |
|
Status |
Active, not recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
May 17, 2021 |
Est. completion date |
June 1, 2029 |
Study information
Verified date |
July 2023 |
Source |
Vanderbilt University Medical Center |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial 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.
Description:
The Investigator's global hypothesis, to be tested eventually in an NIH-funded phase III
controlled trial, is that hydroxyurea at a fixed moderate dose of 20 mg/kg is safe and
effective for primary and secondary stroke prevention in young adults with SCA. Prior to
testing this global hypothesis, the Investigators must develop a multi-disciplinary team that
provides medical care for young adults with SCD and establish the clinical epidemiology of
neurological morbidity in this distinct age group. Building upon the existing research
platforms of ongoing NINDS-funded primary stroke prevention trials in Nigeria, the
Investigators are uniquely positioned to extend their stroke assessment and treatment to the
next sequential age group, young adults with SCA.
The immediate goals of this project are 1) to estimate the prevalence of neurological
morbidity in young adults with SCA (R21 application to NIH); 2) to establish a prospective
cohort of young adults to determine the incidence of neurological morbidity, and 3) to
determine the safety and feasibility of fixed moderate dose of hydroxyurea therapy for
prevention of further neurological disease in young adults with SCA in Nigeria.
The leadership of the current pediatric primary and secondary stroke prevention trials
(NCT01801423, NCT02560935, NCT02675790) in Nigeria will apply a similar effective strategy
used in the Investigator's previous pediatric NINDS-R21 and current pediatric NINDS-R01 to
estimate the prevalence and incidence of neurological morbidity in young adults with SCA.
Young adults with SCA have different stroke risk factors than children less than 16 years of
age with SCA, including risk factors for stroke seen in the general population resulting in
the need for age and disease-specific evidence-based management for primary and secondary
stroke prevention strategies.
the Investigators propose to enroll 250 participants with SCA between 16-25 years of age. The
Investigators believe this sample size is sufficient to estimate the prevalence of stroke and
SCI. This cohort will be followed for 12-18 months to determine the short-term incidence of
strokes and SCI. The Investigators do not intend to calculate a precise incidence of these
neurological injuries due to the short duration of the follow-up.
For young adults with SCIs, strokes, and elevated TCD measurements (based on the pediatric
threshold of abnormal ≥200 cm/s in the middle cerebral artery or terminal portion of the
internal carotid) the Investigators will initially offer regular blood transfusion therapy as
standard care. If they refuse, the Investigators will offer a dose of 20 mg/kg/day of
hydroxyurea for at least one year of therapy. The hydroxyurea will be supplied free of charge
with monthly follow-up.