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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.
This is a Sub-Protocol to the Core Clinical Study Protocol titled: REcovering from COVID-19 Lingering symptoms Adaptive Integrative Medicine (RECLAIM)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hi-OxSR device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | Baseline/Start of intervention to two months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| suzanne Cohen | Contact | 1-866-673-2524 | reclaim@uhn.ca |
| Name | Affiliation | Role |
|---|---|---|
| Angela M Cheung, MD, PhD | University Health Network, Toronto | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kaye Edmonton Clinic | Not yet recruiting | Edmonton | Alberta | Canada |
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| ID | Term |
|---|---|
| D000094024 | Post-Acute COVID-19 Syndrome |
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
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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.
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Participants are not be blinded to group allocation, and will know what group they are assigned to. Participants will be masked to the hypothesis of the study.
| Hi-Ox device | Device | The Hi-Ox mask is connected to a portable oxygen concentrator. |
|
| 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 | 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. | 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) | 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. | 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. | 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). | 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. | 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. | 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. | 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. | 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. | 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 | 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. | Baseline/start of intervention to 2 weeks, 1, 2 and 6 months |
| University Health Network | Recruiting | Toronto | Ontario | M5G 2C4 | Canada |
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| Centre Hospitalier Universitaire de Sherbrooke | Not yet recruiting | Sherbrooke | Quebec | Canada |
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| D007239 |
| Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D000094025 | Post-Infectious Disorders |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |