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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a non-invasive treatment for Long COVID, focusing on symptoms such as brain fog. Researchers aim to understand how short- and long-term exposure to different breathing techniques, including increased carbon dioxide and reduced oxygen, can help. Participants will experience these methods in various sequences to determine which has the best effects. This study is suitable for English speakers diagnosed with Long COVID, excluding those with certain heart, lung, or neurological conditions. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could enhance treatment options for Long COVID.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that non-invasive treatments for long COVID, such as brain stimulation and hyperbaric oxygen therapy, have been tested for safety. Studies have found these treatments are generally well-tolerated, with only mild side effects reported. For instance, hyperbaric oxygen therapy, which involves breathing pure oxygen in a pressurized room, has been used safely for various conditions, with side effects typically limited to ear discomfort or temporary changes in vision.

In other studies on non-invasive brain stimulation, side effects were minimal, including mild headaches or slight skin irritation. These findings suggest that the treatments in this trial, involving low oxygen levels (hypoxia) and high carbon dioxide levels (hypercapnia), are likely to be well-tolerated as well. However, since this trial is in an early phase, the complete safety profile is still under investigation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores non-invasive methods to address brain fog associated with Long COVID, a condition that currently lacks targeted treatments. Unlike traditional options like cognitive therapy or medication aimed at symptom relief, this trial investigates the potential of Progressive Carbon Dioxide and Intermittent Hypoxia exposure to directly influence brain function and improve cognitive symptoms. These methods work by potentially enhancing oxygen delivery and neuroplasticity, offering a novel approach that could provide quicker relief and fewer side effects compared to existing therapies.

What evidence suggests that this trial's treatments could be effective for Long COVID?

This trial will explore non-invasive treatments for Long COVID symptoms, including brain fog. Research has shown that brief periods of low oxygen (intermittent hypoxia) and gradually increasing carbon dioxide exposure might help alleviate these symptoms. Participants in this trial will be assigned to different arms, receiving these interventions in various sequences. One study found that these methods can reduce pain and improve the quality of life for people with ongoing COVID-19 effects. Another study discovered that poor lung function might be linked to brain fog in Long COVID patients, suggesting that better lung performance could help. These treatments aim to enhance lung function, which might lead to improved brain function and fewer symptoms. While more research is needed, these early findings are promising for those suffering from Long COVID. ^{6 7 8 9 10}

Who Is on the Research Team?

Courtney Wheatley-Guy

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8662118/

Long COVID syndrome‐associated brain fog - PMC We investigated the frequency of brain fog in a large cohort of patients with documented coronavirus disease‐2019 (COVID‐19) who have survived the illness.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11900126/

Individualized Algorithm-Based Intermittent Hypoxia ... In this study, a personalized, algorithm-based IHHC alleviated pain and improved quality of life in patients suffering from persistent long-term sequelae after ...

3. nature.com nature.com/articles/s41392-023-01640-z

The long-term health outcomes, pathophysiological ... We comprehensively review the current literature on long COVID, highlighting its epidemiological understanding, the impact of vaccinations, organ-specific ...

4. rsna.org rsna.org/media/press/i/2547

Long COVID Brain Fog Linked to Lung Function The results showed that lower pulmonary gas exchange may be associated with cognitive dysfunction, as well as lower gray matter and white matter ...

5. cidrap.umn.edu cidrap.umn.edu/covid-19/sluggish-gas-exchange-lungs-may-be-involved-long-covid-brain-fog

Sluggish gas exchange in the lungs may be involved ... Lower rates of gas exchange in the lungs may contribute to impaired cognitive function ("brain fog") tied to long COVID, according to a small study.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11051078/

Effects of Hyperbaric Oxygen Therapy on Long COVID The most common symptom is fatigue, presenting in up to 60% of patients with long COVID [1]. “Brain fog” is a set of symptoms, including ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06082518

Study Details | NCT06082518 | Improving Post COVID-19 ... Hyperbaric oxygen therapy involves placing patients in a small chamber where they receive high oxygen gas levels. However, this treatment is expensive and time- ...

8. amjmed.com amjmed.com/article/S0002-9343(24)00468-6/fulltext

Non-Invasive Brain Stimulation for Post-COVID-19 ... We aim to summarize the current evidence for the effectiveness of non-invasive or minimally invasive brain stimulation techniques in reducing symptoms of post- ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002934324004686

Non-Invasive Brain Stimulation for Post-COVID-19 ... We aim to summarize the current evidence for the effectiveness of non-invasive or minimally invasive brain stimulation techniques in reducing symptoms of post- ...

10. bmjopen.bmj.com bmjopen.bmj.com/content/14/5/e083868

Efficacy and safety of hyperbaric oxygen therapy for long ... This systematic review and meta-analysis aim to better investigate the overall efficacy and safety of HBOT for long COVID.