Metabolic and Hemodynamic Reserve in Pediatric SCA

NCT04406818 | Recruiting

• 2 other identifiers: 202106016R01NS121065
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Gray Matter cortical thickness

  Mean whole brain cortical thickness on high resolution T1 images

  3 years

Secondary Outcomes (2)

• Total Brain volume

  3 years

• Cerebrovascular Reactivity

  15 minutes

Study Arms (2)

Healthy Control

ACTIVE COMPARATOR

Drug: Carbon Dioxide

Sickle Cell Anemia

ACTIVE COMPARATOR

Drug: Carbon Dioxide

Interventions

Carbon Dioxide DRUG

Participants inhale carbon dioxide while in magnetic resonance imaging scan to measure cerebrovascular reactivity

Healthy Control; Sickle Cell Anemia

Eligibility Criteria

• Age: 4 Years - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Washington University in St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

MeSH Terms

Conditions

Brain Diseases; Anemia, Sickle Cell

Interventions

Carbon Dioxide

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Carbon Compounds, Inorganic; Inorganic Chemicals; Gases; Oxides; Oxygen Compounds

Study Officials

• Kristin P Guilliams, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristin P Guilliams, MD

CONTACT

3144546120; kristinguilliams@wustl.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2020
• First Posted: May 28, 2020
• Study Start: June 30, 2021
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: September 5, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF
• Time Frame: At study conclusion
• Access Criteria: Upon request by qualified researchers

Locations

US (1)