Clinical trial NCT06928506: Effect of Hi-OxSR for the Treatment of Post COVID Condition (RECLAIM-HiOxSR)
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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Long COVID
Post COVID-19 Condition
Post Acute Sequelae of COVID-19
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2025-04-15
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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)

Eligibility criteria: 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.

Primary outcomes:
measure: Simple reaction time (SRT) task from the TestMyBrain (TMB) Digital Neuropsychology Toolkit On-line survey tool
timeFrame: Baseline/Start of intervention to two months
measure: Verbal paired associates (VPA) task from the TestMyBrain (TMB) Digital Neuropsychology Toolkit On-line survey tool
timeFrame: Baseline/Start of intervention to two months
Secondary outcomes:
measure: All cognitive performance tasks (measured by the TESTMYBRAIN.org (TMB) neuropsychology toolkit
timeFrame: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
measure: Brain Fog Questionnaire
timeFrame: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
measure: Brief Fatigue Inventory
timeFrame: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
measure: Short Form (SF)-36
timeFrame: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
measure: Safety, adverse events and serious adverse events
timeFrame: Baseline/start of intervention to 6 months
measure: Symptom Checklist
timeFrame: Baseline/start of intervention to 2 and 6 months
measure: The DePaul Symptom Post-Exertional Malaise Short Form DSQ-PEM
timeFrame: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
measure: Dyspnea
timeFrame: Baseline/start of intervention to 2 and 6 months
measure: Mental Health - General Anxiety Assessment Form (GAD-7)
timeFrame: Baseline/start of intervention to 2 and 6 months
measure: Mental Health - Patient Health Questionnaire (PHQ-9)
timeFrame: Baseline/start of intervention to 2 and 6 months
measure: Mental Health -Post-traumatic Stress Disorder Checklist (PCL-5)
timeFrame: Baseline/start of intervention to 2 and 6 months
measure: Reintegration to Normal Living Index (RNLI)
timeFrame: Baseline/start of intervention to 2 and 6 months
measure: Blood samples
timeFrame: Baseline/start of intervention and 2 months
measure: Fatigue Scale (adapted from the De Paul Symptom Questionnaire (DSQ2)
timeFrame: Baseline/start of intervention to 2 weeks, 1, 2 and 6 months
Other outcomes:
Locations:
Study officials:
affiliation: University Health Network, Toronto
name: Angela M Cheung, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: