Cerebral Oxygen Metabolism in Children (COMIC)

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.

We 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 can do varies by age. The brain's blood flow changes in small ways during everyday activities, such as normal brain growth, exercise, or deep concentration. 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 as much oxygen as it wants may cause the brain to grow and develop more slowly than it should.

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, and potential neuropsychological assessments. It is also possible that the study team will use a special mask to control the amount of carbon dioxide the participants breathe in so they don't breathe in too much.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease; Cerebral Stroke
• Intervention / Treatment: Other: Carbon Dioxide

Detailed Description

The purpose of the study is to identify imaging biomarkers for brain tissue under high metabolic stress at risk for permanent injury. We will measure CBF, OEF, and CVR in children with and without perturbations in cerebral oxygen delivery over time to determine each parameter's role in clinical and radiologic neurologic outcomes. Measuring CBF and OEF can be done with specialized MRI sequences. Measuring CVR requires a vasoactive response, such as carbon dioxide. In order to delivery carbon dioxide evenly and as safely as possible, we will use an MRI-compatible device to prevent over-breathing carbon dioxide and allow rapid steady-state physiology to minimize total scan time.

• Study Type: Interventional
• Enrollment (Anticipated): 350
• Phase: Not Applicable

Contacts and Locations

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

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Healthy Controls:

• Healthy controls ages 3-50 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 3-50 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

Extracorporeal Membrane Oxygenation (ECMO) Survivors:

• Ages 3-50 years of age
• History of cannulation for ECMO
• Able to participate in MRI scan without sedation
• Not currently pregnant
• Not on vasodilatory medication, such as sildenafil or verapamil

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy Controls	Other: Carbon Dioxide; Participants inhale carbon dioxide while in magnetic resonance imaging scan to measure cerebrovascular reactivity
Active Comparator: Extracorporeal Membrane Oxygenation survivors	Other: Carbon Dioxide; Participants inhale carbon dioxide while in magnetic resonance imaging scan to measure cerebrovascular reactivity
Active Comparator: Sickle Cell Anemia participants	Other: 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	Time Frame
Cerebral Oxygen Metabolism	From the beginning of the MRI scan to the completion of the MRI scan -- 75 minutes.

Secondary Outcome Measures

Outcome Measure	Time Frame
Cerebrovascular Reactivity	From administration of carbon dioxide to end of inhalation of carbon dioxide -- 15 minutes.

Collaborators and Investigators

• Sponsor: Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2019
• Primary Completion (Anticipated): December 1, 2027
• Study Completion (Anticipated): December 1, 2027

Study Registration Dates

• First Submitted: November 6, 2019
• First Submitted That Met QC Criteria: November 6, 2019
• First Posted (Actual): November 8, 2019

Study Record Updates

• Last Update Posted (Actual): November 9, 2021
• Last Update Submitted That Met QC Criteria: November 8, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; sickle cell disease; extracorporeal membrane oxygenation; cerebrovascular reactivity; healthy controls
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Stroke; Anemia, Sickle Cell
• Other Study ID Numbers: 201905044

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No