Cerebral Oxygen Metabolism in Children (COMIC)

• ClinicalTrials.gov Identifier: NCT04157179
• Recruitment Status: Recruiting
• First Posted: November 8, 2019
• Last Update Posted: January 31, 2023
• Sponsor: Washington University School of Medicine
• Information provided by (Responsible Party): Washington University School of Medicine

Tracking Information

• First Submitted Date: November 6, 2019
• First Posted Date: November 8, 2019
• Last Update Posted Date: January 31, 2023
• Actual Study Start Date: October 17, 2019
• Estimated Primary Completion Date: December 2027 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 6, 2019): Cerebral Oxygen Metabolism [ Time Frame: From the beginning of the MRI scan to the completion of the MRI scan -- 75 minutes. ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: November 6, 2019): Cerebrovascular Reactivity [ Time Frame: From administration of carbon dioxide to end of inhalation of carbon dioxide -- 15 minutes. ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cerebral Oxygen Metabolism in Children
• Official Title: Cerebral Oxygen Metabolism in Children

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.

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.

• 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
• Study Phase: Not Applicable

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

All arms will receive the same study conditions.

Masking: None (Open Label)
Primary Purpose: Basic Science

Condition

• Sickle Cell Disease
• Cerebral Stroke

Intervention

Other: Carbon Dioxide

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

Study Arms

• Active Comparator: Healthy Controls
  Intervention: Other: Carbon Dioxide
• Active Comparator: Extracorporeal Membrane Oxygenation survivors
  Intervention: Other: Carbon Dioxide
• Active Comparator: Sickle Cell Anemia participants
  Intervention: Other: Carbon Dioxide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 6, 2019): 350
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2027
• Estimated Primary Completion Date: December 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Years to 50 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04157179
• Other Study ID Numbers: 201905044
• 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
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• 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: Not Provided
• Investigators: Not Provided
• PRS Account: Washington University School of Medicine
• Verification Date: January 2023