Magnetic Resonance Spectroscopy Studies of Acute Hypoxic and Hyperoxic Breathing in Healthy Volunteers

This study evaluates the impact of hypoxic and hyperoxic breathing on measures of brain redox balance and metabolism in healthy individuals. All participants will undergo an MRI scan during administration of air mixtures with different oxygen concentrations to collect the brain measures.

Study Overview

• Status: Withdrawn
• Conditions: Healthy
• Intervention / Treatment: Other: 16% O2 gas in breathed air; Other: 26% O2 gas in breathed air

Detailed Description

Molecular oxygen (O2) constitutes 21% of the air people breathe at sea level. But humans can safely be exposed to somewhat lower and higher concentrations of oxygen. The varying amounts of oxygen entering the body modulate the oxygen available in tissue, ultimately leading to change in redox balance and metabolism. The investigators recently developed non-invasive MRI-based techniques to quantify redox balance and ATP generation in the brain. These processes are thought to be abnormal in people with psychiatric disorders.

In this study, the investigators aim to manipulate the concentration of oxygen in the breathed air in 2 separate MRI scans on consecutive days (16% and 26%). The investigators anticipate that healthy individuals will demonstrate changes in brain redox balance and metabolism in response to these modulations.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Belmont, Massachusetts, United States, 02478
      • McLean Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female individuals age between 18 and 40 years old
• BMI between 19 and 29 kg/m2
• Having capacity to consent to the study

Exclusion Criteria:

• Under 18 or over 40 Family history of psychiatric illness among first degree relatives (parents, siblings, or children)
• Delirium secondary to medical illness
• Any contraindication to MR scan, including claustrophobia, pregnancy, etc.
• Medical condition that might endanger the subject during or after a blood draw (e.g. hemophilia)
• Significant medical or neurological illness
• Prior high altitude pulmonary edema (HAPE) or high-altitude cerebral edema (HACE) diagnosis Born at altitudes greater than 2,100 m (~7,000 ft) Systemic disease with or without any functional limitation; including controlled hypertension controlled diabetes without systemic effects any cardiac conditions with or without functional limitation, such as, coronary artery disease or valve disease Pregnancy determined by urine pregnancy test, detecting presence of human chorionic gonadotropin (hCG), less than six weeks postpartum, or planning to conceive during the study period.

Women who are not willing to receive serum pregnancy tests Active smoking and tobacco chewers. Volunteers may be enrolled if they quit smoking for more than 1 year.

Excess alcohol use: more than ½ L/day of wine consumption or equivalent Any current medication use except oral contraceptives. Living in areas that are more than 1,200 m (~4,000 feet), or have traveled to areas that are more than 1,200 m for more than four days within the last 2 months Anemia, as defined by hemoglobin < 10g/dL Abnormal hemoglobin (e.g. presence of hemoglobin S) Evidence of apnea or other sleeping disorders Evidence of asthma Lower respiratory infection within the last 30 days Not willing to have blood drawn from an arm vein each test day of the study Claustrophobia (inability to tolerate MRI scan or wear a facemask) Currently enrolled in another research study Facial abnormalities that would preclude proper use of a face mask Hb<12

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Healthy subjects; 16% O2 gas in breathed air for 30 minutes 26% O2 gas in breathed air for 30 minutes

Other: 16% O2 gas in breathed air; Inspiratory gas mixtures: Hypoxic inspiratory gas will be obtained by adding nitrogen (N2) to normobaric, normoxic air with medical N2 tanks. Delivery of gas mixture: The gas mixture will be delivered by standard tight facemask.; Other: 26% O2 gas in breathed air; Inspiratory gas mixtures: Hyperoxic inspiratory gas will be obtained by adding oxygen (O2) to normobaric, normoxic air with medical O2 tanks. Delivery of gas mixture: The gas mixture will be delivered by standard tight facemask.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NAD+/NADH ratio	NAD+ and NADH concentrations are measured using 31P MRS scanning	During 30 minute hypoxic/hyperoxic exposure portion of the MRS scan

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CK Kf	Reaction rate of the creatine kinase enzyme measured using 31P MRS scanning	During 30 minute hypoxic/hyperoxic exposure portion of the MRS scan
PCr	Phosphocreatine concentration measured using 31P MRS scanning	During 30 minute hypoxic/hyperoxic exposure portion of the MRS scan
Pi	Inorganic phosphate concentration measured using 31P MRS scanning	During 30 minute hypoxic/hyperoxic exposure portion of the MRS scan
ATP	ATP concentration measured using 31P MRS scanning	During 30 minute hypoxic/hyperoxic exposure portion of theMRS scan

Collaborators and Investigators

• Sponsor: Mclean Hospital
• Investigators: Principal Investigator: Dost Ongur, MD PhD, McLean Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 29, 2023
• Primary Completion (Estimated): August 29, 2023
• Study Completion (Estimated): August 29, 2023

Study Registration Dates

• First Submitted: March 29, 2017
• First Submitted That Met QC Criteria: April 3, 2017
• First Posted (Actual): April 10, 2017

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Respiratory Aspiration
• Other Study ID Numbers: 2017P000328

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No