Trial Outcomes & Findings for Metabolic Changes in the Activated Human Visual Cortex During Mild Hypoxia (NCT NCT02482571)

Results Overview

Relative change in glutamate concentration from rest to visual stimulation as measured by fMRS (with water suppression) in the primary visual cortex during conditions of normoxia.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

25 participants

Primary outcome timeframe

Baseline and Visual Stimulation at 4 minutes

Results posted on

2019-03-19

Participant Flow

Participant milestones

Participant milestones
Measure	Mild Hypoxia Mild Hypoxia: During normoxia, the computer-controlled gas blender provides a gas mixture that generates pressures of expired O2 and CO2 similar to the resting values measured for each subject (32-35mmHg and 100-110 mmHg, respectively). During mild hypoxia, we will target the same expired CO2 of normoxia and a 60 mmHg reduction of expired O2 from the resting value (to a minimum limit of 50 mmHg), which is expected to reduce arterial oxygen saturation to 82-85%. In mild hypoxia, the fraction of inspired oxygen is reduced from \~21% (room air) to \~12%. During both conditions of normoxia and mild hypoxia, the brain activity of subjects is monitored with functional MRI (fMRI) and functional MRS (fMRS) during visual stimuli.
Overall Study STARTED	25
Overall Study COMPLETED	17
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Mild Hypoxia Mild Hypoxia: During normoxia, the computer-controlled gas blender provides a gas mixture that generates pressures of expired O2 and CO2 similar to the resting values measured for each subject (32-35mmHg and 100-110 mmHg, respectively). During mild hypoxia, we will target the same expired CO2 of normoxia and a 60 mmHg reduction of expired O2 from the resting value (to a minimum limit of 50 mmHg), which is expected to reduce arterial oxygen saturation to 82-85%. In mild hypoxia, the fraction of inspired oxygen is reduced from \~21% (room air) to \~12%. During both conditions of normoxia and mild hypoxia, the brain activity of subjects is monitored with functional MRI (fMRI) and functional MRS (fMRS) during visual stimuli.
Overall Study Adverse Event	1
Overall Study Scanner or Respiract failure	3
Overall Study Withdrawal by Subject	4

Baseline Characteristics

Metabolic Changes in the Activated Human Visual Cortex During Mild Hypoxia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mild Hypoxia n=25 Participants During normoxia, the computer-controlled gas blender provides a gas mixture that generates pressures of expired O2 and CO2 similar to the resting values measured for each subject (32-35mmHg and 100-110 mmHg, respectively). During mild hypoxia, we will target the same expired CO2 of normoxia and a 60 mmHg reduction of expired O2 from the resting value (to a minimum limit of 50 mmHg), which is expected to reduce arterial oxygen saturation to 82-85%. In mild hypoxia, the fraction of inspired oxygen is reduced from \~21% (room air) to \~12% (equivalent to an altitude of 4000 meters). During both conditions of normoxia and mild hypoxia, the brain activity of subjects is monitored with functional magnetic resonance spectroscopy (fMRS) while they are presented with visual stimuli.
Age, Continuous	25.4 years STANDARD_DEVIATION 5.9 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Visual Stimulation at 4 minutes

Population: Out of the 17 experimental sessions that were successfully completed, 4 had data of insufficient quality. Therefore, a total of 13 sessions was used for final analyses.

Relative change in glutamate concentration from rest to visual stimulation as measured by fMRS (with water suppression) in the primary visual cortex during conditions of normoxia.

Outcome measures

Outcome measures
Measure	Mild Hypoxia n=13 Participants Mild Hypoxia: During normoxia, the computer-controlled gas blender provides a gas mixture that generates pressures of expired O2 and CO2 similar to the resting values measured for each subject (32-35mmHg and 100-110 mmHg, respectively). During mild hypoxia, we will target the same expired CO2 of normoxia and a 60 mmHg reduction of expired O2 from the resting value (to a minimum limit of 50 mmHg), which is expected to reduce arterial oxygen saturation to 82-85%. In mild hypoxia, the fraction of inspired oxygen is reduced from \~21% (room air) to \~12%. During both conditions of normoxia and mild hypoxia, the brain activity of subjects is monitored with functional MRI (fMRI) and functional MRS (fMRS) during visual stimuli.
Change in Glutamate Concentration During a Visual Stimulus Measured by fMRS at Normoxia	4 percentage of concentration (micromol/g) Standard Deviation 2.4

PRIMARY outcome

Timeframe: Baseline and Visual Stimulation at 4 minutes

Population: Out of the 17 experimental sessions that were successfully completed, 4 had data of insufficient quality. Therefore, a total of 13 sessions was used for final analyses.

Relative change in glutamate concentration from rest to visual stimulation as measured by fMRS (with water suppression) in the primary visual cortex during conditions of hypoxia.

Outcome measures

Outcome measures
Measure	Mild Hypoxia n=13 Participants Mild Hypoxia: During normoxia, the computer-controlled gas blender provides a gas mixture that generates pressures of expired O2 and CO2 similar to the resting values measured for each subject (32-35mmHg and 100-110 mmHg, respectively). During mild hypoxia, we will target the same expired CO2 of normoxia and a 60 mmHg reduction of expired O2 from the resting value (to a minimum limit of 50 mmHg), which is expected to reduce arterial oxygen saturation to 82-85%. In mild hypoxia, the fraction of inspired oxygen is reduced from \~21% (room air) to \~12%. During both conditions of normoxia and mild hypoxia, the brain activity of subjects is monitored with functional MRI (fMRI) and functional MRS (fMRS) during visual stimuli.
Change in Glutamate Concentration During a Visual Stimulus Measured by Functional MRS at Hypoxia	2.9 percentage of concentration (micromol/g) Standard Deviation 1.9

SECONDARY outcome

Timeframe: Baseline and Visual Stimulation at 30 seconds

Population: Out of the 17 experimental sessions that were successfully completed, 4 had data of insufficient quality. Therefore, a total of 13 sessions was used for final analyses.

Relative change in water signal intensity from rest to visual stimulation as measured by fMRS (without water suppression) in the primary visual cortex during conditions of normoxia.

Outcome measures

Outcome measures
Measure	Mild Hypoxia n=13 Participants Mild Hypoxia: During normoxia, the computer-controlled gas blender provides a gas mixture that generates pressures of expired O2 and CO2 similar to the resting values measured for each subject (32-35mmHg and 100-110 mmHg, respectively). During mild hypoxia, we will target the same expired CO2 of normoxia and a 60 mmHg reduction of expired O2 from the resting value (to a minimum limit of 50 mmHg), which is expected to reduce arterial oxygen saturation to 82-85%. In mild hypoxia, the fraction of inspired oxygen is reduced from \~21% (room air) to \~12%. During both conditions of normoxia and mild hypoxia, the brain activity of subjects is monitored with functional MRI (fMRI) and functional MRS (fMRS) during visual stimuli.
Brain Activity Measured by Blood Oxygenation Level Dependent (BOLD) Signal at Normoxia	3.3 percentage of signal intensity Standard Deviation 2.0

SECONDARY outcome

Timeframe: Baseline and Visual Stimulation at 30 seconds

Population: Out of the 17 experimental sessions that were successfully completed, 4 had data of insufficient quality. Therefore, a total of 13 sessions was used for final analyses.

Relative change in water signal intensity from rest to visual stimulation as measured by fMRS (without water suppression) in the primary visual cortex during conditions of hypoxia.

Outcome measures

Outcome measures
Measure	Mild Hypoxia n=13 Participants Mild Hypoxia: During normoxia, the computer-controlled gas blender provides a gas mixture that generates pressures of expired O2 and CO2 similar to the resting values measured for each subject (32-35mmHg and 100-110 mmHg, respectively). During mild hypoxia, we will target the same expired CO2 of normoxia and a 60 mmHg reduction of expired O2 from the resting value (to a minimum limit of 50 mmHg), which is expected to reduce arterial oxygen saturation to 82-85%. In mild hypoxia, the fraction of inspired oxygen is reduced from \~21% (room air) to \~12%. During both conditions of normoxia and mild hypoxia, the brain activity of subjects is monitored with functional MRI (fMRI) and functional MRS (fMRS) during visual stimuli.
Brain Activity Measured by Blood Oxygenation Level Dependent (BOLD) Signal at Hypoxia	1.2 percentage of signal intensity Standard Deviation 1.2

Adverse Events

Mild Hypoxia

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Mild Hypoxia n=25 participants at risk Mild Hypoxia: During normoxia, the computer-controlled gas blender provides a gas mixture that generates pressures of expired O2 and CO2 similar to the resting values measured for each subject (32-35mmHg and 100-110 mmHg, respectively). During mild hypoxia, we will target the same expired CO2 of normoxia and a 60 mmHg reduction of expired O2 from the resting value (to a minimum limit of 50 mmHg), which is expected to reduce arterial oxygen saturation to 82-85%. In mild hypoxia, the fraction of inspired oxygen is reduced from \~21% (room air) to \~12% (equivalent to an altitude of 4000 meters). During both conditions of normoxia and mild hypoxia, the brain activity of subjects is monitored with functional MRI (fMRI) and functional MRS (fMRS) during visual stimuli.
Musculoskeletal and connective tissue disorders Muscle cramp	4.0% 1/25 • Number of events 1

Other adverse events

Other adverse events
Measure	Mild Hypoxia n=25 participants at risk Mild Hypoxia: During normoxia, the computer-controlled gas blender provides a gas mixture that generates pressures of expired O2 and CO2 similar to the resting values measured for each subject (32-35mmHg and 100-110 mmHg, respectively). During mild hypoxia, we will target the same expired CO2 of normoxia and a 60 mmHg reduction of expired O2 from the resting value (to a minimum limit of 50 mmHg), which is expected to reduce arterial oxygen saturation to 82-85%. In mild hypoxia, the fraction of inspired oxygen is reduced from \~21% (room air) to \~12% (equivalent to an altitude of 4000 meters). During both conditions of normoxia and mild hypoxia, the brain activity of subjects is monitored with functional MRI (fMRI) and functional MRS (fMRS) during visual stimuli.
Psychiatric disorders Claustropobia	8.0% 2/25
Psychiatric disorders Nervousness	32.0% 8/25
General disorders Sleepiness	24.0% 6/25
General disorders Lightheadedness	8.0% 2/25
General disorders Metallic Taste	8.0% 2/25
General disorders Cold	16.0% 4/25
General disorders Warmth	8.0% 2/25

Additional Information

Silvia Mangia, PhD

University of Minnesota

Phone: 6126254920

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place