Clinical trial NCT04406818: Metabolic and Hemodynamic Reserve in Pediatric SCA
Official title: The Role of Metabolic and Hemodynamic Reserve in Age-Related Brain Vulnerability in Pediatric Sickle Cell Anemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Child, Only
Brain Diseases
Sickle Cell Disease
Anemia, Sickle Cell
Keywords: sickle cell anemia
cerebrovascular reactivity
cerebral oxygen metabolism
cortical thickness
gray matter
carbon dioxide
magnetic resonance imaging
brain development
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2020-05-28
Enrollment: 120
Sex: ALL
Minimum age (years): 4
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this research study is to better understand how blood flow and metabolism change can influence brain development in the early decades of life. SCA participants and healthy controls are age and sex-matched for comparison. Within the SCA cohort, children with infarcts may have thinner cortices than those without, reflecting a greater loss.

The investigators will examine brain blood flow and metabolism using magnetic resonance imaging (MRI). The brain's blood vessels expand and constrict to regulate blood flow based on the brain's needs. The amount of expanding and contracting the blood vessels may vary by age. The brain's blood flow changes in small ways during everyday activities, such exercise, deep concentration, or normal brain growth. Significant illness or psychological stress may increase the brain's metabolic demand or cause other bigger changes in blood flow. If blood vessels are not able to expand to give more blood flow when metabolic demand is high, the brain may not get all of the oxygen it needs. In extreme circumstances, if the brain is unable to get enough oxygen for a long time, a stroke may occur. Sometimes small strokes occur without other noticeable changes and are only detectable on an MRI. These are sometimes called "silent strokes." In less extreme circumstances, not having a full oxygen supply may cause the brain to grow and develop more slowly than when it has a full supply.

One way to test the ability of blood vessels to expand is by measuring blood flow while breathing in carbon dioxide. Carbon dioxide causes blood vessels in the brain to dilate without increasing brain metabolism.

During this study participants may be asked to undergo a blood draw, MRI, cognitive assessments, and brief questionnaires. The study team will use a special mask to control the amount of carbon dioxide the participants breathe in.


Eligibility criteria: Healthy Controls:

* Healthy controls ages 4-21 years of age
* Able to participate in MRI scan without sedation
* Not currently pregnant
* No significant psychiatric history, defined as having a severe psychiatric diagnosis, per PI discretion
* No history of epilepsy
* No history of stroke or cerebrovascular disease
* May have occasional headaches if not taking a daily preventative medication for headaches
* Not on vasodilatory medication, such as sildenafil or verapamil

Sickle Cell Anemia Participants:

* Ages 4-21 years of age
* Hb SS or SBeta-thal
* Able to participate in MRI scan without sedation
* Not currently pregnant
* Not on vasodilatory medication, such as sildenafil or verapamil
* No known vasculopathy

Primary outcomes:
measure: Gray Matter cortical thickness
timeFrame: 3 years
Secondary outcomes:
measure: Total Brain volume
timeFrame: 3 years
measure: Cerebrovascular Reactivity
timeFrame: 15 minutes
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Kristin P Guilliams, MD
role: PRINCIPAL_INVESTIGATOR
References: