Non-Invasive Treatment for Post-COVID Syndrome

Overseen By Jordan Parks

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Disqualifiers: Neurological disease, Stroke, Heart failure, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 29

45 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment for post-COVID syndrome?

Research shows that hyperbaric oxygen therapy can improve cognitive function, psychiatric symptoms, pain, and fatigue in patients with post-COVID-19 condition by increasing brain blood flow and promoting brain healing. ^{1 2 3 4 5}

Is hyperbaric oxygen therapy safe for humans?

Hyperbaric oxygen therapy has been used in studies for post-COVID conditions and has shown improvements in cognitive and psychiatric symptoms without reported safety concerns, suggesting it is generally safe for humans. ^{1 2 3 4 6}

How does the Non-Invasive Treatment for Long COVID Brain Fog differ from other treatments for post-COVID syndrome?

This treatment is unique because it includes hyperbaric oxygen therapy, which can improve brain function and reduce symptoms like fatigue and pain by increasing oxygen flow to the brain and promoting brain healing. Unlike other treatments, it specifically targets brain connectivity and neuroplasticity, which are crucial for cognitive and emotional recovery in post-COVID patients. ^{1 2 3 4 7}

What is the purpose of this trial?

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

Research Team

Courtney Wheatley-Guy

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for English-speaking individuals who have been diagnosed with Long COVID and are experiencing mental fatigue. It's not suitable for those with a history of neurological diseases, severe lung or heart conditions, uncontrolled asthma, blood clots, kidney or liver disease, pregnant women, or those with a BMI over 40.

Inclusion Criteria

I have been diagnosed with Long COVID.

English speaking

Exclusion Criteria

I have a history of a brain-related disease like dementia or Alzheimer's.

I have had an aneurysm in the past.

My asthma is severe and not under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Acute Exposure

Participants undergo acute exposure to hypoxia and hypercapnia through various interventions including Placebo, Progressive Carbon Dioxide, and Intermittent Hypoxia

14 days

Multiple visits during the 14-day intervention period

Training

Participants complete 6 cycles of either progressive CO2 ramp protocol or the intermittent hypoxia protocol for 60 minutes per visit

14 days

Multiple visits during the 14-day training period

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit within 7 days of final training visit

Treatment Details

Interventions

• Non-invasive Treatment for Long COVID Brain Fog

Trial Overview The study is testing the effects of non-invasive treatments on brain fog in Long COVID patients. These include acute and training sessions with progressive carbon dioxide ramping (hypercapnia), intermittent hypoxic exposure (low oxygen), and placebo controls to compare results.

Participant Groups

Group I: Training Group Experimental Treatment 2 Interventions

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

Group II: Acute exposure: Progressive Carbon Dioxide, Placebo, Intermittent Hypoxia Experimental Treatment 3 Interventions

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

Group III: Acute exposure: Progressive Carbon Dioxide, Intermittent Hypoxia, Placebo Experimental Treatment 3 Interventions

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

Group IV: Acute exposure: Placebo, Progressive Carbon Dioxide, Intermittent Hypoxia Experimental Treatment 3 Interventions

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

Group V: Acute exposure: Placebo, Intermittent Hypoxia, Progressive Carbon Dioxide Experimental Treatment 3 Interventions

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

Group VI: Acute exposure: Intermittent Hypoxia, Progressive Carbon Dioxide, Placebo Experimental Treatment 3 Interventions

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

Group VII: Acute exposure: Intermittent Hypoxia, Placebo, Progressive Carbon Dioxide Experimental Treatment 3 Interventions

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

Group VIII: Placebo Group Placebo Group 1 Intervention

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

Non-invasive Treatment for Long COVID Brain Fog is already approved in European Union, United States for the following indications:

Approved in European Union as Non-invasive Neuromodulation for:

• Post-COVID-19 Condition
• Brain Fog

Approved in United States as Non-invasive Neuromodulation for:

• Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)
• Brain Fog

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

In a randomized trial with 73 post-COVID-19 patients, hyperbaric oxygen therapy (HBOT) significantly improved cognitive functions, energy levels, sleep quality, psychiatric symptoms, and pain interference after 40 treatment sessions.

The improvements were linked to changes in brain MRI perfusion and microstructural alterations in key brain areas, suggesting that HBOT promotes neuroplasticity and enhances brain function in individuals suffering from lingering symptoms after COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial. Zilberman-Itskovich, S., Catalogna, M., Sasson, E., et al.[2022]

A 55-year-old man with long COVID symptoms showed significant improvements in cognitive functions and physical capacity after 60 sessions of hyperbaric oxygen therapy, suggesting its potential as a treatment option.

Improvements included enhanced memory, attention, and exercise capacity, which correlated with increased cerebral blood flow, indicating that hyperbaric oxygen therapy may help address the underlying mechanisms of long COVID.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen treatment for long coronavirus disease-19: a case report. Bhaiyat, AM., Sasson, E., Wang, Z., et al.[2022]

Hyperbaric oxygen therapy has been shown to enhance cognitive function, reduce psychiatric symptoms, and alleviate pain and fatigue in patients suffering from post-COVID-19 condition.

The positive effects of this therapy are likely due to improved blood flow to the brain and increased neuroplasticity in areas responsible for cognitive and emotional processing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric Oxygen Improves Neurocognitive Function and Symptoms of Post-COVID Condition. Rosenberg, K.[2022]

In a randomized, sham-controlled trial involving 73 post-COVID-19 patients, hyperbaric oxygen therapy (HBOT) was found to improve brain connectivity, particularly in areas related to cognitive and emotional recovery.

HBOT led to significant changes in both functional and structural connectivity in the brain, suggesting it may help address neurological symptoms experienced by patients after COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of hyperbaric oxygen therapy on functional and structural connectivity in post-COVID-19 condition patients: A randomized, sham-controlled trial. Catalogna, M., Sasson, E., Hadanny, A., et al.[2022]

Intranasal immunotherapy using bioactive substances from M2 macrophages was well tolerated and showed significant improvement in olfactory function in 7 patients with long-term post-COVID-19 hyposmia, with results measured at baseline and follow-ups of 1 and 6-12 months.

At the 6- to 12-month follow-up, 5 out of 7 patients reported high satisfaction with their restored ability to perceive and recognize odors, indicating that this therapy may be an effective treatment for chronic olfactory impairment following COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal immunotherapy with M2 macrophage soluble factors in post-COVID hyposmia: A pilot study. Shevela, EY., Davydova, MN., Meledina, IV., et al.[2023]

In a study involving 10 patients with long COVID, hyperbaric oxygen therapy (HBOT) significantly improved fatigue and cognitive functions after 10 treatment sessions, indicating its potential as an effective intervention.

Statistical analysis showed very large effect sizes in fatigue reduction and substantial improvements in cognitive areas such as attention and executive function, suggesting that HBOT could be a promising treatment for debilitating long COVID symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen therapy for the treatment of long COVID: early evaluation of a highly promising intervention. Robbins, T., Gonevski, M., Clark, C., et al.[2023]

In a study of 43 patients with persistent olfactory dysfunction after COVID-19, 12 weeks of classical olfactory training (COT) led to significant improvements in olfactory sensitivity, with 40% of participants showing clinically meaningful gains compared to only 6% in the control group.

The effectiveness of COT in improving smell was consistent across various factors such as age, gender, and duration of olfactory dysfunction, suggesting it is a broadly applicable treatment for post-COVID-19 olfactory issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of classical olfactory training in patients with COVID-19-related persistent loss of smell. Yaylacı, A., Azak, E., Önal, A., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen treatment for long coronavirus disease-19: a case report. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Hyperbaric Oxygen Improves Neurocognitive Function and Symptoms of Post-COVID Condition. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of hyperbaric oxygen therapy on functional and structural connectivity in post-COVID-19 condition patients: A randomized, sham-controlled trial. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Intranasal immunotherapy with M2 macrophage soluble factors in post-COVID hyposmia: A pilot study. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen therapy for the treatment of long COVID: early evaluation of a highly promising intervention. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Effects of classical olfactory training in patients with COVID-19-related persistent loss of smell. [2023]