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

Not Applicable

Not yet recruiting

• Conditions: Long COVID; Post COVID-19 Condition; Post Acute Sequelae of COVID-19

• Registration Number: NCT06928506
• Lead Sponsor: University Health Network, Toronto

Brief 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 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.

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 Timeline

• Status Verified: 2025-02
• Study Start: 2025-04
• Study First Submitted: 2025-04-11
• Study First Submitted QC: 2025-04-11
• Last Update Submitted: 2025-04-11
• Study First Posted: 2025-04-15
• Last Update Posted: 2025-04-15
• Primary Completion: 2027-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 120

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Simple reaction time (SRT) task from the TestMyBrain (TMB) Digital Neuropsychology Toolkit On-line survey tool	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.
Verbal paired associates (VPA) task from the TestMyBrain (TMB) Digital Neuropsychology Toolkit On-line survey tool	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.

Secondary Outcome Measures

Name	Time	Method
All cognitive performance tasks (measured by the TESTMYBRAIN.org (TMB) neuropsychology toolkit	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.
Brain Fog Questionnaire	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
Brief Fatigue Inventory	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.
Short Form (SF)-36	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)
Safety, adverse events and serious adverse events	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.
Symptom Checklist	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.
The DePaul Symptom Post-Exertional Malaise Short Form DSQ-PEM	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).
Dyspnea	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.
Mental Health - General Anxiety Assessment Form (GAD-7)	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.
Mental Health - Patient Health Questionnaire (PHQ-9)	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.
Mental Health -Post-traumatic Stress Disorder Checklist (PCL-5)	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.
Reintegration to Normal Living Index (RNLI)	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.
Blood samples	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
Fatigue Scale (adapted from the De Paul Symptom Questionnaire (DSQ2)	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.