COMIC: Cerebral Oxygen Metabolism in Children

Sponsor

Washington University School of Medicine (Other)

Overall Status

Recruiting

CT.gov ID

NCT04157179

Collaborator

(none)

350

Enrollment

Location

Arms

97.5

Anticipated Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease Cerebral Stroke	Other: Carbon Dioxide	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

350 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

All arms will receive the same study conditions.All arms will receive the same study conditions.

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Cerebral Oxygen Metabolism in Children

Actual Study Start Date :

Oct 17, 2019

Anticipated Primary Completion Date :

Dec 1, 2027

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Cerebral Oxygen Metabolism [From the beginning of the MRI scan to the completion of the MRI scan -- 75 minutes.]

Secondary Outcome Measures

Cerebrovascular Reactivity [From administration of carbon dioxide to end of inhalation of carbon dioxide -- 15 minutes.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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