Recruiting

Non-invasive TreatmentNon-invasive Treatment for Long COVID (Post COVID-19 Condition) Brain Fog

Sponsor:

Mayo Clinic

Code:

NCT06614309

Conditions

Long COVID

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Acute Placebo Visit

Acute Progressive Carbon Dioxide

Acute Intermittent Hypoxia

Training: Progressive Carbon Dioxide Ramping

Training: Intermittent Hypoxic Exposure

Study Details

Brief summary:

This study aims to assess the effects of both acute and chronic exposures to hypoxia and hypercapnia in patients with Long COVID syndrome.

Conditions

Long COVID

Study ID

NCT06614309

Start date

Sep 24, 2024

Status verified date

Jun, 2026

Completion date

Dec, 2026

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion criteria:

English speaking
Diagnosis of Long COVID

Exclusion criteria:

Any history of:

Coronary artery dissection or aortic dissection
Neurological disease (e.g. dementia, Alzheimer's disease, or other brain-related disease)
Cerebrovascular disease or stroke
Aneurysm
If currently has:

Moderate-severe chronic obstructive pulmonary disease
Uncontrolled moderate-severe asthma
Moderate-severe bronchiectasis
Moderate-severe interstitial lung disease, requiring the use of supplemental oxygen
A necessity to use supplemental oxygen, for any reason
New or worsening symptoms (decompensation) of heart failure
Right heart disease due to chronic pulmonary disease/sleep apnea
Uncontrolled myocardial ischemia or angina
Uncontrolled heart arrhythmias
Heart or lung infection (e.g. myocarditis or pericarditis)
Left main coronary artery stenosis
Moderate-severe aortic stenosis
Pulmonary embolism, pulmonary infarction, or other blood clots
Severe respiratory disease
Chronic kidney disease
Chronic liver disease
Females of childbearing potential will complete a urine pregnancy test at their baseline visit to rule out pregnancy
BMI >40
Study staff unable to obtain adequate signal for cerebral blood flow

Study Design

Enrollment

45 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Acute exposure: Placebo, Progressive Carbon Dioxide, Intermittent Hypoxia

Study group will receive the three interventions in this order: Placebo, Progressive Carbon Dioxide, then Intermittent Hypoxia

experimental: Acute exposure: Placebo, Intermittent Hypoxia, Progressive Carbon Dioxide

Study group will receive the three interventions in this order: Placebo, Intermittent Hypoxia, Progressive Carbon Dioxide

experimental: Acute exposure: Intermittent Hypoxia, Placebo, Progressive Carbon Dioxide

Study group will receive the three interventions in this order: Intermittent Hypoxia, Placebo, Progressive Carbon Dioxide

experimental: Acute exposure: Intermittent Hypoxia, Progressive Carbon Dioxide, Placebo

Study group will receive the three interventions in this order: Intermittent Hypoxia, Progressive Carbon Dioxide, Placebo

experimental: Acute exposure: Progressive Carbon Dioxide, Placebo, Intermittent Hypoxia

Study group will receive the three interventions in this order: Progressive Carbon Dioxide, Placebo, Intermittent Hypoxia

experimental: Acute exposure: Progressive Carbon Dioxide, Intermittent Hypoxia, Placebo

Study group will receive the three interventions in this order: Progressive Carbon Dioxide, Intermittent Hypoxia, Placebo

placebo comparator: Placebo Group

Study group will complete 6 simulated cycles of 5 minutes breathing 21% oxygen from a douglas bag and 5 minutes breathing room air (60 minutes) for every visit during the 14 days intervention period. Subjects will then return within 7 days of their final training visit to repeat baseline testing

experimental: Training Group

Training Study group will be complete 6 cycles of either progressive CO2 ramp protocol or the intermittent hypoxia protocol for 60 minutes for every visit during the 14 days. Subjects will then return within 7 days of their final training visit to repeat baseline testing

Interventions

Acute Placebo Visit

The placebo visit will include 6 simulated cycles of 5 minutes breathing 21% oxygen from a douglas bag and 5 minutes breathing room air.

Acute Progressive Carbon Dioxide

The progressive carbon dioxide visit will include a 60-minute progressive ramp which includes 6 cycles of progressive CO2 ramping starting at 0% and progressing up to 10% within 5 minutes immediately followed with 5 minutes of room air breathing in between cycles.

Acute Intermittent Hypoxia

The intermittent hypoxia exposure visit will include 6 cycles breathing 8-12% oxygen (O2) for 5 minutes with a target pulse oximeter saturation of 86-90%, followed by 5 minutes of breathing room air.

Training: Progressive Carbon Dioxide Ramping

Intervention will consist of 6 to 10 study visits (3-5 sessions/week) to be completed within 14 days. Subjects will will be given the progressive CO2 ramp protocol of 60-minute sessions, which will include 6 cycles of progressive CO2 ramping starting at 0% and progressing up to 10% within 5 minutes immediately followed with 5 minutes of room air breathing in between cycles, for every visit during the 14 days.

Training: Intermittent Hypoxic Exposure

Intervention will consist of 6 to 10 study visits (3-5 sessions/week) to be completed within 14 days. Subjects will will be given the intermittent hypoxia exposure protocol of 60-minute sessions, which will include 6 cycles breathing 8-12% oxygen (O2) for 5 minutes with a target pulse oximeter saturation of 86-90%, followed by 5 minutes of breathing room air for every visit during the 14 days.

Training: Placebo Control

Intervention will consist of 6 to 10 study visits (3-5 sessions/week) to be completed within 14 days. Subjects will complete 6 simulated cycles of 5 minutes breathing 21% oxygen from a douglas bag and 5 minutes breathing room air (60 minutes) for every visit during the 14 days.

Primary outcome measure

Change in cerebral blood flow [ Time Frame: Baseline, post-acute exposure and 14 days post training ]
Change in heart rate variability [ Time Frame: Baseline, post-acute exposure and 14 days post training ]
Change in brain fog scale [ Time Frame: Baseline, post-acute exposure and 14 days post training ]

Central Contacts and Locations

Central contacts

Jordan Parks

480-301-6616 parks.jordan@mayo.edu

Locations

Mayo Clinic in Arizona

Recruiting

Scottsdale, Arizona, United States, 85259

Contacts

Jordan Parks

480-301-6616 parks.jordan@mayo.edu

Principal Investigator:

Courtney M Wheatley-Guy, PhD

More Information

Sponsor

Mayo Clinic

Last update posted

Jun 5, 2026

Last verified

Jun, 2026

Keywords

brain fog
brain blood flow
heart rate variability
fatigue

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2026-06-05.