Improving Post COVID-19 Syndrome With Hyperbaric Oxygen Treatments (PCS-HBOT)

Improving Post COVID-19 Syndrome With Hyperbaric Oxygen Treatments (PCS-HBOT Study)

Over 500 million people have been infected with COVID-19, and to date, more than 6 million people have died. Many individuals who have recovered from COVID-19 continue to experience symptoms even after they have been "cured" of the disease. This condition is known as post COVID-19 condition, which can have serious health consequences. A common symptom among these individuals is chronic fatigue, characterized by persistent tiredness or lack of energy. This study aims to explore a novel treatment for symptoms of post COVID-19 condition, known as hyperbaric oxygen therapy. This approach has shown promise in helping people with post COVID-19 conditions and treating some other causes of fatigue.

Hyperbaric oxygen therapy involves placing patients in a small chamber where they receive high oxygen gas levels. However, this treatment is expensive and time-consuming, and it is unclear if this treatment can be effectively assessed in a large-scale research study. This small study will help us decide if conducting a large research study is feasible. The investigators aim to assess if hyperbaric oxygen therapy can improve symptoms of post COVID-19 condition, such as fatigue.

Study Overview

• Status: Recruiting
• Conditions: COVID-19; Fatigue; Fatigue Syndrome, Chronic; Post-COVID-19 Syndrome; Post COVID-19 Condition; Post-COVID Syndrome
• Intervention / Treatment: Device: Monoplace Hyperbaric Chamber (Class III medical device).

Detailed Description

Over 500 million individuals worldwide have contracted COVID-19. Among those that have 'recovered' from the acute infection, many suffer from post-COVID-19 condition (experiencing 1 or more symptoms 3 months from the onset of acute COVID-19 infection, with symptoms lasting at least 2 months). Many of these common symptoms, including fatigue, myalgia, and difficulty focusing ('brain fog'), can seriously compromise one's quality of life.

Existing treatments predominantly focus on supportive management and specific symptom control, and most approaches have mixed or limited effectiveness. Recently, hyperbaric oxygen therapy (HBOT), acknowledged for its anti-inflammatory effects, has emerged as a potential treatment for post-COVID-19 condition symptoms. However, HBOT is time and resource-intensive, requiring between 20-40 daily treatments. Therefore, the feasibility of assessing HBOT efficacy via a large-scale randomized controlled trial is still being determined. Hence, this study aims to evaluate adherence to the protocol and the feasibility of proceeding with the full trial. The goal of the full trial will be to evaluate the impact of HBOT treatment on post-COVID-19 condition symptoms.

This prospective, crossover, randomized pilot trial enrolls adult patients officially diagnosed with post-COVID-19 condition by a healthcare practitioner who continue to experience symptoms, particularly fatigue, at least 3 months following their initial COVID-19 infection. Participants will be assigned randomly (stratified by sex) to either begin HBOT treatments immediately or after a 60-day interval. All patients will be followed for 12 months from the start of treatment, with assessments at the time of enrollment (baseline), start of treatment (if starting 60 days after enrollment), 4 weeks after the start of treatment, and every 2 months from the first HBOT treatment for 1 year. A subjective questionnaire regarding patient satisfaction will also be completed after the last HBOT treatment session and at 1 year after the start of treatment.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fahad Alam, MD; Phone Number: 416-480-4864; Email: fahad.alam@sunnybrook.ca
• Study Contact Backup: Name: Lilia Kaustov, PhD; Phone Number: 89607 416 480-6100; Email: lilia.kaustov@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Sub-Investigator: Peter Giacobbe, MD
      • Contact: Fahad Alam, MD; Phone Number: 416-480-4864; Email: fahad.alam@sunnybrook.ca
      • Principal Investigator: Jordan Tarshis, MD,FRCPC
      • Sub-Investigator: Oskar Singer, MD,FRCPC
      • Sub-Investigator: Stephen Choi, MD,FRCPC
      • Sub-Investigator: Stanley Hamstra, PhD
      • Sub-Investigator: Adrienne Chan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years old
2. Officially diagnosed with post COVID-19 condition by a healthcare practitioner
3. At least three months since SARS-CoV-2 infection

4. Symptoms that persist more than 12 weeks:

   • Chronic fatigue (must include) along with one of the following symptoms:
   • Difficulty thinking or problem solving ('brain fog')
   • Stress or anxiety

Exclusion Criteria:

1. Contraindications/medically unfit to receive hyperbaric treatments at an outpatient facility (pneumothorax, in-patients, requiring infusions to maintain hemodynamics, active and unstable coronary disease)
2. Patients with cognitive difficulties and/or mental retardation before COVID diagnosis
3. History of traumatic brain injury
4. Unlikely to comply with follow-up assessments (e.g. no fixed address, plans to move out of town)
5. Known pregnancy or planning a pregnancy in women of childbearing age

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immediate start of hyperbaric treatments; HBOT treatments will be scheduled to start immediately after referral.	Device: Monoplace Hyperbaric Chamber (Class III medical device).; 40 hyperbaric oxygen therapy (HBOT) treatments (90 minute exposures at 2 atmospheres (ATM) per treatment), scheduled daily from Monday to Friday (i.e., 5 treatments per week) until treatments are completed (approximately 8 weeks). Treatments will be delivered in a medical grade, Health Canada-approved monoplace hyperbaric chamber and overseen by specialist hyperbaric physicians and a Certified Hyperbaric Technologist. Device is being used in manner consistent with approved usage in Canada.
Experimental: Delayed start of hyperbaric treatments; HBOT treatments will be scheduled to start 60 days after referral.	Device: Monoplace Hyperbaric Chamber (Class III medical device).; 40 hyperbaric oxygen therapy (HBOT) treatments (90 minute exposures at 2 atmospheres (ATM) per treatment), scheduled daily from Monday to Friday (i.e., 5 treatments per week) until treatments are completed (approximately 8 weeks). Treatments will be delivered in a medical grade, Health Canada-approved monoplace hyperbaric chamber and overseen by specialist hyperbaric physicians and a Certified Hyperbaric Technologist. Device is being used in manner consistent with approved usage in Canada.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rate - referral	Quantify referral rate from healthcare providers	9 months
Recruitment rate - inclusion	Number of patients meeting inclusion criteria	9 months
Recruitment rate - consent	Patient consent rate	9 months
Adherence to HBOT protocol	Number of Participants received minimum 4 treatments per week with >35 treatments	9 months recruitment + 8 weeks treatment
Adherence to HBOT protocol - satisfaction	Subjective patient satisfaction questionnaire inquiring about HBOT experience, barriers to and promoters of treatment	After last HBOT treatment and at 12 month follow-up
Feasibility of Clinical Outcome Measures	Feasibility of implementation of clinical outcome scales (PDQ, FSS, SF-36) to be completed at the time of enrollment (baseline), start of treatment (if starting 60 days after enrollment), 4 weeks after the start of treatment, and every 2 months from the first HBOT treatment for 1 year.	Up to 1 year after start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The impact of HBOT on post COVID-19 condition - PDQ	The validated clinical deficit scale, Perceived Deficits Questionnaire (PDQ), will be used at the time of enrollment (baseline), start of treatment (if starting 60 days after enrollment), 4 weeks after the start of treatment, and every 2 months from the first HBOT treatment for 1 year	Up to 1 year after start of treatment
The impact of HBOT on post COVID-19 condition - FSS	The validated clinical deficit scale, Fatigue Severity Scale (FSS), will be used at the time of enrollment (baseline), start of treatment (if starting 60 days after enrollment), 4 weeks after the start of treatment, and every 2 months from the first HBOT treatment for 1 year	Up to 1 year after start of treatment
The impact of HBOT on post COVID-19 condition - SF-36	The validated clinical deficit scale, QoL Short Form Survey (SF-36), will be used at the time of enrollment (baseline), start of treatment (if starting 60 days after enrollment), 4 weeks after the start of treatment, and every 2 months from the first HBOT treatment for 1 year.	Up to 1 year after start of treatment
The impact of time to initiation of HBOT on outcomes following initial infection outcome - PDQ	Validated clinical deficit scales PDQ will be compared with FSS and SF-36 between immediate and delayed start groups	Up to 1 year after start of treatment
The impact of time to initiation of HBOT on outcomes following initial infection outcome - FSS	Validated clinical deficit scale FSS will be compared with PDQ and SF-36 between immediate and delayed start groups	Up to 1 year after start of treatment
The impact of time to initiation of HBOT on outcomes following initial infection outcome - SF-36	Validated clinical deficit scale SF-36 will be compared with PDQ and FSS between immediate and delayed start groups	Up to 1 year after start of treatment
Initial infection severity as a mediator of HBOT impact - PDQ	Validated clinical deficit scale PDQ will be compared relative to baseline scores	Up to 1 year after start of treatment
Initial infection severity as a mediator of HBOT impact - FSS	Validated clinical deficit scale FSS will be compared relative to baseline scores	Up to 1 year after start of treatment
Initial infection severity as a mediator of HBOT impact - SF-36	Validated clinical deficit scale SF-36 will be compared relative to baseline scores	Up to 1 year after start of treatment
Long-term symptomatic impact at 1 year - PDQ	Assessed using validated clinical deficit scale PDQ at 12 months after start of treatment	12 month follow-up
Long-term symptomatic impact at 1 year - FSS	Assessed using validated clinical deficit scale FSS at 12 months after start of treatment	12 month follow-up
Long-term symptomatic impact at 1 year - SF-36	Assessed using validated clinical deficit scales SF-36 at 12 months after start of treatment	12 month follow-up

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Investigators: Principal Investigator: Fahad Alam, MD, Sunnybrook Health Sciences Centre; Principal Investigator: Jordan Tarshis, MD, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: September 11, 2023
• First Submitted That Met QC Criteria: October 12, 2023
• First Posted (Actual): October 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Fatigue; COVID-19; Hyperbaric Oxygen Therapy; HBOT; Post COVID-19 Condition; Severe Acute Respiratory Syndrome-CoV-2
• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Post-Infectious Disorders; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Pathologic Processes; Encephalomyelitis; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; COVID-19; Post-Acute COVID-19 Syndrome; Fatigue Syndrome, Chronic; Fatigue
• Other Study ID Numbers: 5825

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be available upon request to study PIs following publication.
• IPD Sharing Time Frame: Upon publication, no limit on time.
• IPD Sharing Access Criteria: Contact directly study principal investigators.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes