Effect of Hi-OxSR for the Treatment of Post COVID Condition (RECLAIM-HiOxSR)

September 11, 2025 updated by: University Health Network, Toronto

RECLAIM: Recovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine Trial - Effect of Hi-OxSR for the Treatment of Post COVID Condition (RECLAIM-HiOxSR)

The RECLAIM study platform will be used to explore whether the use of the Hi-OxSR device improves the symptoms of post covid cognitive dysfunction. Carbon dioxide (CO2) has been proposed as a potential treatment for persistent immune activation as there is evidence that CO2 has antioxidant, anti-inflammatory, and anti-cytokine effects. We conducted a pilot study assessing the open label use of re-breathing CO2 (using Hi-OxSR) twice a day for 14 days, for the treatment of post-COVID cognitive dysfunction. Significant improvements were found in multiple cognitive assessments using TestMyBrain cognitive tests and brain fog (MSNQ) and fatigue scores. This phase 2 clinical trial seeks to build on current findings to determine the optimal effective dose of treatment (i.e. length of use, oxygen concentration, without or without CO2 rebreathing) and the safety of using Hi-OxSR in this patient population.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a Sub-Protocol to the Core Clinical Study Protocol titled: REcovering from COVID-19 Lingering symptoms Adaptive Integrative Medicine (RECLAIM)

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Suzanne Cohen
  • Phone Number: 1-866-673-2524
  • Email: RECLAIM@uhn.ca

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
        • Recruiting
        • University Health Network
        • Contact:
    • Quebec

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥18 years;
  2. Positive COVID-19 test by nasopharyngeal swab RT-PCR (reverse transcription polymerase chain reaction) test, antibody or antigen tests at least 3 months prior to randomization; OR Presumed COVID-19 assessed by the site investigator (no positive COVID-19 test) with acute illness after October 15, 2019.
  3. Patients should be treated with standard of care therapies (as discussed in the study manual) for at least 4 weeks prior to entry into trial.
  4. Lingering COVID-19 symptoms beyond 3 months from onset of acute COVID and symptoms have lasted at least 2 months. The onset of COVID is considered the earliest of two dates: the date of positive test or the date of first symptoms;
  5. Lingering symptoms from COVID-19 present at the time of randomization. "Lingering symptoms of Long COVID" must include self-reported cognitive dysfunction symptoms.
  6. Female patients of childbearing potential (as assessed by the overseeing Investigator) who are sexually active must agree to practice true abstinence or use effective methods of contraception while on study treatment. Effective methods of contraception must be discussed and approved by the overseeing Investigator.
  7. Must be able to provide informed consent and both willing and able to comply with study requirements.
  8. Oxygen saturation on room air ≥92% at screening measured by pulse oximeter.

Exclusion Criteria:

  1. Patients who had mechanical ventilation or extracorporeal membrane oxygen (ECMO) for COVID-19;
  2. Current end-organ failure, organ transplantation, or current hospitalization in acute care hospital;
  3. Contraindications to all of the study interventions;
  4. Co-enrolment in another interventional trial (co-enrolment in an observational study is permitted);
  5. Currently pregnant or breastfeeding.
  6. Known physician diagnosis of cognitive dysfunction prior to COVID infection
  7. Use of an investigational drug/device or other interventions within 30 days of screening
  8. Use of home oxygen (O2) at baseline
  9. History of pulmonary hypertension
  10. Interstitial pulmonary fibrosis
  11. Moderate to severe chronic obstructive pulmonary disease (COPD)
  12. History of narcolepsy
  13. Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the participant or the quality of the data.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Group 1
Use of Hi-OxSR for 30 minutes twice a day at low oxygen flow (0.5-3 liters per minute) for 2 weeks.
Device: Hi-OxSR device
The Hi-OxSR device consists of the Hi-Ox mask connected to a portable oxygen concentrator, with added tubing serving as a reservoir for rebreathed exhaled breath.
Experimental: Group 2
Use of Hi-OxSR for 30 minutes twice a day at low oxygen flow (0.5-3 liters per minute) for 4 weeks.
Device: Hi-OxSR device
The Hi-OxSR device consists of the Hi-Ox mask connected to a portable oxygen concentrator, with added tubing serving as a reservoir for rebreathed exhaled breath.
Active Comparator: Group 3
Use of Hi-Ox for 30 minutes twice a day at high oxygen flow (5 liters per minute) for 2 weeks.
Device: Hi-Ox device
The Hi-Ox mask is connected to a portable oxygen concentrator.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Simple reaction time (SRT) task from the TestMyBrain (TMB) Digital Neuropsychology Toolkit On-line survey tool
Time Frame: Baseline/Start of intervention to two months
TestMyBrain was developed as a tool to collect large, population-based samples for understanding the relationship between cognition, emotion, social functioning, and health. This test will take about 5 minutes to complete and will assess reaction time.
Baseline/Start of intervention to two months
Verbal paired associates (VPA) task from the TestMyBrain (TMB) Digital Neuropsychology Toolkit On-line survey tool
Time Frame: Baseline/Start of intervention to two months
TestMyBrain was developed as a tool to collect large, population-based samples for understanding the relationship between cognition, emotion, social functioning, and health. This test will take about 5 minutes to complete and will assess memory.
Baseline/Start of intervention to two months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Blood samples
Time Frame: Baseline/start of intervention and 2 months
Blood samples will be used in correlative studies using advanced multi-omic and machine learning methods to better understand our results so as to identify phenotypes that will benefit from specific therapies
Baseline/start of intervention and 2 months
All cognitive performance tasks (measured by the TESTMYBRAIN.org (TMB) neuropsychology toolkit
Time Frame: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
TestMyBrain was developed as a tool to collect large, population-based samples for understanding the relationship between cognition, emotion, social functioning, and health. This test battery will take about 20 minutes to complete and will assess: verbal, episodic and working memory, attention, processing speed, basic psychomotor response speed, and cognitive control.
Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
Brain Fog Questionnaire
Time Frame: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
(Adapted from MSNQ) This is a self-administered 15-item questionnaire that assesses neurocognitive function. It takes approximately less than 5 minutes to complete
Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
Brief Fatigue Inventory
Time Frame: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
The self-administered Brief Fatigue Inventory is composed of 9 items evaluated on a 10-point scale, assessing severity of fatigue and impact of fatigue on daily life. It takes approximately 2-3 minutes to complete.
Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
Short Form (SF)-36
Time Frame: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
Mental health related quality of life, measured by the Mental Composite Score (MCS), and physical health-related quality of life, measured by the Physical Component Score (PCS) of the SF-36 (v.1)
Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
Safety, adverse events and serious adverse events
Time Frame: Baseline/start of intervention to 6 months
Safety of the Hi-OxSR device will be reported through Adverse Events (AEs) and Serious Adverse Events (SAEs) throughout the study period.
Baseline/start of intervention to 6 months
Symptom Checklist
Time Frame: Baseline/start of intervention to 2 and 6 months
Symptom Checklist (adapted from the De Paul Symptom Questionnaire (DSQ2), the World Health Organization Global COVID-19 Clinical Platform's Post COVID-19 case report form (CRF) and the Symptom Burden Questionnaire for Long COVID): to track symptom trajectory.
Baseline/start of intervention to 2 and 6 months
The DePaul Symptom Post-Exertional Malaise Short Form DSQ-PEM
Time Frame: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
The self-administered DSQ-PEM is comprised of two sections assessing post-exertional malaise (PEM): (i) frequency and severity of PEM (5 questions), (ii) consequences, symptoms and recovery (5 questions).
Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
Dyspnea
Time Frame: Baseline/start of intervention to 2 and 6 months
Assessed using the Borg Dyspnea scale. This short assessment tool assesses perceived shortness of breath on exertion using a 10 point scale as assessed by the patient.
Baseline/start of intervention to 2 and 6 months
Mental Health - General Anxiety Assessment Form (GAD-7)
Time Frame: Baseline/start of intervention to 2 and 6 months
The GAD-7 is a valid and efficient tool for screening for generalized anxiety disorder and assessing its severity in clinical practice and research. It is an easy-to-use, self-administered patient questionnaire that can be completed in minutes.
Baseline/start of intervention to 2 and 6 months
Mental Health - Patient Health Questionnaire (PHQ-9)
Time Frame: Baseline/start of intervention to 2 and 6 months
The PHQ-9 is a validated, multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. It incorporates Diagnostic and Statistical Manual IV (DSM-IV) depression diagnostic criteria with other leading major depressive symptoms into a brief self-report tool. The PHQ-9 is brief and useful in clinical practice.
Baseline/start of intervention to 2 and 6 months
Mental Health -Post-traumatic Stress Disorder Checklist (PCL-5)
Time Frame: Baseline/start of intervention to 2 and 6 months
The PCL-5 is a validated, reliable, 20-item self-report measure that assesses the 20 Diagnostic and Statistical Manual 5 (DSM-5) symptoms of Post-Traumatic Stress Disorder (PTSD). It takes approximately 5-10 minutes to complete.
Baseline/start of intervention to 2 and 6 months
Reintegration to Normal Living Index (RNLI)
Time Frame: Baseline/start of intervention to 2 and 6 months
This short self-administered assessment tool will determine the degree to which participants reintegrate into normal social activities such as recreation, mobility in the community and interaction in family and other relationships. This tool has been validated in community living adults with mobility limitations.
Baseline/start of intervention to 2 and 6 months
Fatigue Scale (adapted from the De Paul Symptom Questionnaire (DSQ2)
Time Frame: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
The Fatigue Scale was adapted from the De Paul Symptom Questionnaire (DSQ2)'s 38 questions assessing medical history of Myalgia encephalomyelitis/chronic fatigue syndrome (ME/CFS), comorbidities, medications, impact on quality of life and daily activities, etc.
Baseline/start of intervention to 2 weeks, 1, 2 and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Health Network, Toronto

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Angela m Cheung, MD, PhD, University Health Network, Toronto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 11, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 11, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 15, 2025

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 15, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 11, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 21-6203-HiOxSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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