Long COVIDRECLAIM-HiOxSRNCT06928506
Effect of Hi-OxSR for the Treatment of Post COVID Condition
A study testing Hi-OxSR device and Hi-Ox device in people with Long COVID and Post COVID-19 Condition, run by University Health Network, Toronto at 3 sites in Canada.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Long COVID, Post COVID-19 Condition, Post Acute Sequelae of COVID-19
- What is being tested?
- Hi-OxSR device and Hi-Ox device
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 3 sitesCanada
- Study dates
- 1 Aug 2025to Apr 2029
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years;
- 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.
- 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.
- 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;
- Lingering symptoms from COVID-19 present at the time of randomization. "Lingering symptoms of Long COVID" must include self-reported cognitive dysfunction symptoms.
- 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.
- Must be able to provide informed consent and both willing and able to comply with study requirements.
- Oxygen saturation on room air ≥92% at screening measured by pulse oximeter.
Who cannot join
- Patients who had mechanical ventilation or extracorporeal membrane oxygen (ECMO) for COVID-19;
- Current end-organ failure, organ transplantation, or current hospitalization in acute care hospital;
- Contraindications to all of the study interventions;
- Co-enrolment in another interventional trial (co-enrolment in an observational study is permitted);
- Currently pregnant or breastfeeding.
- Known physician diagnosis of cognitive dysfunction prior to COVID infection
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- Use of an investigational drug/device or other interventions within 30 days of screening
- Use of home oxygen (O2) at baseline
- History of pulmonary hypertension
- Interstitial pulmonary fibrosis
- Moderate to severe chronic obstructive pulmonary disease (COPD)
- History of narcolepsy
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada3 sites, 3 recruiting
- Recruiting
Kaye Edmonton Clinic
Edmonton, Alberta
Parisa Bayat, Parisa.Bayat@albertahealthservices.ca
- Recruiting
Centre Hospitalier Universitaire de Sherbrooke
Sherbrooke, Quebec
Christine Coordinator, christine.rioux-perreault.ciussse-chus@ssss.gouv.qc.ca
- Recruiting
University Health Network
Toronto, Ontario, M5G 2C4
Suzanne Cohen, 1-866-673-2524, RECLAIM@uhn.ca
About this study
Official title: 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.
Read the detailed description
This is a Sub-Protocol to the Core Clinical Study Protocol titled: REcovering from COVID-19 Lingering symptoms Adaptive Integrative Medicine (RECLAIM)
- Being tested
- Hi-OxSR device, Hi-Ox device
- Medical subject headings
- Post-Acute COVID-19 Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hi-OxSR deviceDevice
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.
Hi-Ox deviceDevice
The Hi-Ox mask is connected to a portable oxygen concentrator.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Use of Hi-OxSR for 30 minutes twice a day at low oxygen flow (0.5-3 liters per minute) for 2 weeks. Receives: Device: Hi-OxSR device |
| Group 2 | Experimental | Use of Hi-OxSR for 30 minutes twice a day at low oxygen flow (0.5-3 liters per minute) for 4 weeks. Receives: Device: Hi-OxSR device |
| Group 3 | Active comparator | Use of Hi-Ox for 30 minutes twice a day at high oxygen flow (5 liters per minute) for 2 weeks. Receives: Device: Hi-Ox device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Simple reaction time (SRT) task from the TestMyBrain (TMB) Digital Neuropsychology Toolkit On-line survey tool
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.
Measured: Baseline/Start of intervention to two months
Verbal paired associates (VPA) task from the TestMyBrain (TMB) Digital Neuropsychology Toolkit On-line survey tool
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.
Measured: Baseline/Start of intervention to two months
Secondary outcomes (14)
All cognitive performance tasks (measured by the TESTMYBRAIN.org (TMB) neuropsychology toolkit
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.
Measured: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
Brain Fog Questionnaire
(Adapted from MSNQ) This is a self-administered 15-item questionnaire that assesses neurocognitive function. It takes approximately less than 5 minutes to complete
Measured: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
Brief Fatigue Inventory
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.
Measured: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
Short Form (SF)-36
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)
Measured: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
Safety, adverse events and serious adverse events
Safety of the Hi-OxSR device will be reported through Adverse Events (AEs) and Serious Adverse Events (SAEs) throughout the study period.
Measured: Baseline/start of intervention to 6 months
Symptom Checklist
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.
Measured: Baseline/start of intervention to 2 and 6 months
The DePaul Symptom Post-Exertional Malaise Short Form DSQ-PEM
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).
Measured: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
Dyspnea
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.
Measured: Baseline/start of intervention to 2 and 6 months
Mental Health - General Anxiety Assessment Form (GAD-7)
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.
Measured: Baseline/start of intervention to 2 and 6 months
Mental Health - Patient Health Questionnaire (PHQ-9)
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.
Measured: Baseline/start of intervention to 2 and 6 months
Mental Health -Post-traumatic Stress Disorder Checklist (PCL-5)
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.
Measured: Baseline/start of intervention to 2 and 6 months
Reintegration to Normal Living Index (RNLI)
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.
Measured: Baseline/start of intervention to 2 and 6 months
Blood samples
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
Measured: Baseline/start of intervention and 2 months
Fatigue Scale (adapted from the De Paul Symptom Questionnaire (DSQ2)
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.
Measured: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2025
- Study start1 Aug 2025
- Primary completionFeb 2028 (estimated)
- Study completionApr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Long COVIDStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- RECLAIM is a Canada-wide phase ll/lll, prospective, adaptive randomized controlled platform trial that is intended to study various interventions for the treatment of long COVID. Participants in the Hi-OxSR sub-protocol will be randomized in a 1:1:1 ratio to one of 3 arms.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Angela M Cheung, MD, PhD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06928506
- Sponsor's protocol ID
- 21-6203-HiOxSR
- Acronym
- RECLAIM-HiOxSR
- Status last verified
- Oct 2026
- First submitted
- 11 Apr 2025
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No