Metabolic and Hemodynamic Reserve in Pediatric SCA

• ClinicalTrials.gov Identifier: NCT04406818
• Recruitment Status: Recruiting
• First Posted: May 28, 2020
• Last Update Posted: February 21, 2023
• Sponsor: Washington University School of Medicine
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): Washington University School of Medicine

Tracking Information

• First Submitted Date: May 22, 2020
• First Posted Date: May 28, 2020
• Last Update Posted Date: February 21, 2023
• Actual Study Start Date: June 30, 2021
• Estimated Primary Completion Date: March 31, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 27, 2020)

Gray Matter cortical thickness [ Time Frame: 3 years ]

Mean whole brain cortical thickness on high resolution T1 images

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 1, 2021)

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

Original Secondary Outcome Measures (submitted: May 27, 2020)

Total Brain volume [ Time Frame: 3 years ]

Total brain volume (gray matter and white matter) on high resolution T1 image

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Basic Science

Condition

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

Intervention

Drug: Carbon Dioxide

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

Study Arms

• Active Comparator: Healthy Control
  Intervention: Drug: Carbon Dioxide
• Active Comparator: Sickle Cell Anemia
  Intervention: Drug: Carbon Dioxide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 1, 2021): 120
• Original Estimated Enrollment (submitted: May 27, 2020): 250
• Estimated Study Completion Date: March 31, 2026
• Estimated Primary Completion Date: March 31, 2026 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 4 Years to 21 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Kristin P Guilliams, MD; 3144546120; kristinguilliams@wustl.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04406818
• Other Study ID Numbers: 771237; R01NS121065 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: At study conclusion
• Access Criteria: Upon request by qualified researchers

• Current Responsible Party: Washington University School of Medicine
• Original Responsible Party: Same as current
• Current Study Sponsor: Washington University School of Medicine
• Original Study Sponsor: Same as current
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Kristin P Guilliams, MD; Washington University School of Medicine

• PRS Account: Washington University School of Medicine
• Verification Date: February 2023