Metabolic and Hemodynamic Reserve in Pediatric SCA

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

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.

Study Overview

• Status: Recruiting
• Conditions: Brain Diseases; Sickle Cell Disease; Anemia, Sickle Cell; Child, Only
• Intervention / Treatment: Drug: Carbon Dioxide

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kristin P Guilliams, MD; Phone Number: 3144546120; Email: kristinguilliams@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University in St. Louis
      • Contact: Kristin P Guillliams, MD; Phone Number: 314-454-6120; Email: kristinguilliams@wustl.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy Control	Drug: Carbon Dioxide; Participants inhale carbon dioxide while in magnetic resonance imaging scan to measure cerebrovascular reactivity
Active Comparator: Sickle Cell Anemia	Drug: Carbon Dioxide; Participants inhale carbon dioxide while in magnetic resonance imaging scan to measure cerebrovascular reactivity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gray Matter cortical thickness	Mean whole brain cortical thickness on high resolution T1 images	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Brain volume	Total brain volume (gray matter and white matter) on high resolution T1 image	3 years
Cerebrovascular Reactivity	Change in blood flow as measured by MRI in response to carbon dioxide	15 minutes

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Kristin P Guilliams, MD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2021
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: May 22, 2020
• First Submitted That Met QC Criteria: May 27, 2020
• First Posted (Actual): May 28, 2020

Study Record Updates

• Last Update Posted (Actual): August 28, 2023
• Last Update Submitted That Met QC Criteria: August 24, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; sickle cell anemia; carbon dioxide; cerebrovascular reactivity; brain development; cerebral oxygen metabolism; gray matter; cortical thickness
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Brain Diseases; Anemia; Anemia, Sickle Cell
• Other Study ID Numbers: 202106016; R01NS121065 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The proposed research assets will include MRI scan data and CO2 breathing data from 120 subjects, including pediatric subjects. As children are a vulnerable population, the project team will make the data (with any personally identifiable information redacted) available to qualified investigators under a data sharing agreement that provides for (1) a commitment to using for research purposes only, (2) a commitment to securing the data using appropriate computer technology, and (3) a commitment to destroying the data after analyses are completed. This will be available upon request within 6 months of the grant period ending.
• IPD Sharing Time Frame: At study conclusion
• IPD Sharing Access Criteria: Upon request by qualified researchers
• IPD Sharing Supporting Information Type: ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No