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

NCT06614309 | Recruiting

• 1 other identifier: 24-006115
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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

Keywords

brain fog; brain blood flow; heart rate variability; fatigue

Outcome Measures

Primary Outcomes (3)

• Change in cerebral blood flow

  The intracranial middle cerebral arteries will be obtained (MCAv) will be imaged with a linear probe and duplex ultrasound system to simultaneously measure CBFv by pulse wave doppler (peak and mean flow)

  Baseline, post-acute exposure and 14 days post training

• Change in heart rate variability

  Short- term HRV analysis of a 3-lead ECG recording (5 minute recording) will evaluate both time-domain parameters (mean heart rate, standard deviation of normal-to-normal (NN) intervals (SDNN) and root mean square of successive differences between NN intervals rMSSD) and frequency-domain parameters (total power, high frequency (HF) and low frequency (LF) and LF/HF ratio).

  Baseline, post-acute exposure and 14 days post training

• Change in brain fog scale

  Questionnaire assessing of how much brain fog is affecting daily abilities

  Baseline, post-acute exposure and 14 days post training

Secondary Outcomes (6)

• Change in fatigue functional assessment of chronic illness therapy-fatigue scale

  Baseline, post-acute exposure and 14 days post training

• Change in short form health survey (SF-36)

  Baseline, post-acute exposure and 14 days post training

• Change in Trail making test

  Baseline, post-acute exposure and 14 days post training

• Change in rapid cognitive assessment tool (RCAT) score

  Baseline, post-acute exposure and 14 days post training

• Change in Task switching test performance

  Baseline, post-acute exposure and 14 days post training

Study Arms (8)

Acute exposure: Placebo, Progressive Carbon Dioxide, Intermittent Hypoxia

EXPERIMENTAL

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

Other: Acute Placebo Visit; Other: Acute Progressive Carbon Dioxide; Other: Acute Intermittent Hypoxia

Acute exposure: Placebo, Intermittent Hypoxia, Progressive Carbon Dioxide

EXPERIMENTAL

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

Other: Acute Placebo Visit; Other: Acute Progressive Carbon Dioxide; Other: Acute Intermittent Hypoxia

Acute exposure: Intermittent Hypoxia, Placebo, Progressive Carbon Dioxide

EXPERIMENTAL

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

Other: Acute Placebo Visit; Other: Acute Progressive Carbon Dioxide; Other: Acute Intermittent Hypoxia

Acute exposure: Intermittent Hypoxia, Progressive Carbon Dioxide, Placebo

EXPERIMENTAL

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

Other: Acute Placebo Visit; Other: Acute Progressive Carbon Dioxide; Other: Acute Intermittent Hypoxia

Acute exposure: Progressive Carbon Dioxide, Placebo, Intermittent Hypoxia

EXPERIMENTAL

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

Other: Acute Placebo Visit; Other: Acute Progressive Carbon Dioxide; Other: Acute Intermittent Hypoxia

Acute exposure: Progressive Carbon Dioxide, Intermittent Hypoxia, Placebo

EXPERIMENTAL

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

Other: Acute Placebo Visit; Other: Acute Progressive Carbon Dioxide; Other: Acute Intermittent Hypoxia

Placebo Group

PLACEBO COMPARATOR

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

Other: Training: Placebo Control

Training Group

EXPERIMENTAL

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

Other: Training: Progressive Carbon Dioxide Ramping; Other: Training: Intermittent Hypoxic Exposure

Interventions

Acute Placebo Visit OTHER

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

Acute Progressive Carbon Dioxide OTHER

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

Acute Intermittent Hypoxia OTHER

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.

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

Training: Progressive Carbon Dioxide Ramping OTHER

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 Group

Training: Intermittent Hypoxic Exposure OTHER

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 Group

Training: Placebo Control OTHER

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.

Placebo Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• English speaking
• Diagnosis of Long COVID

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

RECRUITING

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Mental Fatigue; Fatigue

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Behavioral Symptoms; Behavior

Study Officials

• Courtney Wheatley-Guy

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jordan Parks

CONTACT

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 24, 2024
• First Posted: September 26, 2024
• Study Start: September 24, 2024
• Primary Completion: April 1, 2026
• Study Completion: May 1, 2026
• Last Updated: November 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)