Metabolic and Hemodynamic Reserve in Pediatric SCA

Sickle Cell Disease Clinical Trial

Official title:

The Role of Metabolic and Hemodynamic Reserve in Age-Related Brain Vulnerability in Pediatric Sickle Cell Anemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04406818
• Other study ID #: 202106016
• Secondary ID: R01NS121065
• Status: Recruiting
• Phase: N/A
• Start date: June 30, 2021
• Est. completion date: March 31, 2026

Study information

• Verified date: August 2023
• Source: Washington University School of Medicine
• Contact: Kristin P Guilliams, MD
• Phone: 3144546120
• Email: kristinguilliams[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: March 31, 2026
• Est. primary completion date: March 31, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 4 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Anemia, Sickle Cell
• Brain Diseases
• Child, Only
• Sickle Cell Disease

Intervention

Drug:
• Carbon Dioxide
Participants inhale carbon dioxide while in magnetic resonance imaging scan to measure cerebrovascular reactivity

Locations

Country	Name	City	State
United States	Washington University in St. Louis	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gray Matter cortical thickness	Mean whole brain cortical thickness on high resolution T1 images	3 years
Secondary	Total Brain volume	Total brain volume (gray matter and white matter) on high resolution T1 image	3 years
Secondary	Cerebrovascular Reactivity	Change in blood flow as measured by MRI in response to carbon dioxide	15 minutes