Hi-OxSR to treat post-COVID cognitive problems

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

This trial will test whether using the Hi-OxSR breathing device can help adults with long COVID who have ongoing cognitive problems and fatigue.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Health Network, Toronto (Academic / other)
• Locations: 3 sites (Edmonton, Alberta and 2 other locations)
• Trial ID: NCT06928506 on ClinicalTrials.gov

What this trial studies

This phase 2 sub-protocol within the RECLAIM platform tests Hi-OxSR and Hi-Ox devices in adults with post-COVID cognitive dysfunction to determine optimal dose, duration, and safety. The trial builds on an open-label pilot where twice-daily CO2 rebreathing with Hi-OxSR for 14 days produced improvements on cognitive tests, brain fog, and fatigue scores. Participants will be assigned to different device settings and usage lengths (varying oxygen concentration and with or without CO2 rebreathing) to identify the most effective and safe approach. The study is conducted at sites in Toronto, Edmonton, and Sherbrooke.

Who should consider this trial

Good fit: Adults aged 18 or older with confirmed or presumed COVID at least three months earlier who continue to have self-reported cognitive dysfunction for at least two months despite standard care would be typical candidates.

Not a fit: People without ongoing cognitive symptoms, those whose COVID occurred less than three months ago, or those with contraindications to rebreathing or supplemental oxygen are unlikely to benefit.

Why it matters

Potential benefit: If successful, it could provide a non-drug breathing therapy that reduces brain fog and fatigue in people with long COVID.

How similar studies have performed: A small open-label pilot using twice-daily Hi-OxSR for 14 days reported significant improvements in cognitive tests, brain fog, and fatigue, but larger randomized data are not yet available.

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.

Where this trial is running

Edmonton, Alberta and 2 other locations

• Kaye Edmonton Clinic — Edmonton, Alberta, Canada (Not_yet_recruiting)
• University Health Network — Toronto, Ontario, Canada (Recruiting)
• Centre Hospitalier Universitaire de Sherbrooke — Sherbrooke, Quebec, Canada (Not_yet_recruiting)

Study contacts

• Principal investigator: Angela M Cheung, MD, PhD — University Health Network, Toronto
• Study coordinator: suzanne Cohen

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