Recovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine Trial - Effect of Hyperbaric Oxygen Therapy for the Treatment of Post COVID Condition

Phase 2

Not yet recruiting

• Conditions: Post COVID Condition; Post Acute Sequelae of COVID-19; Long COVID
• Interventions: Device: Hyperbaric Oxygen therapy

• Registration Number: NCT06452095
• Lead Sponsor: University Health Network, Toronto

Brief Summary

The RECLAIM study platform will be used to explore whether the use of Hyperbaric Oxygen therapy (HBOT) may be used to improve the symptoms of post covid condition.

Hyperbaric oxygen therapy is a well-established medical treatment. HBOT promotes healing by delivering a high concentration of oxygen into the body. This high level of oxygen has a number of known benefits, such as growth of new blood vessels, as well as regulating immune and inflammation responses. It helps protect the brain and other nervous tissue from inflammation. HBOT may also have antiviral effects.

Collectively, it has the potential to target the underlying mechanisms believed to play a critical role in the development of Long COVID.

Many patients with Long COVID complain of fatigue, brain fog, muscle aches and other symptoms. There is evidence to suggest that these symptoms may be a problem with the blood vessels, resulting in abnormal delivery of oxygen to tissues. Thus, our group is investigating whether HBOT's ability to improve the delivery of oxygen to tissues may help these symptoms.

Detailed Description

This is a Sub-Protocol to the Core Clinical Study Protocol titled: REcovering from COVID19 Lingering symptoms Adaptive Integrative Medicine (RECLAIM),

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study First Submitted: 2024-06-07
• Study First Submitted QC: 2024-06-07
• Study First Posted: 2024-06-11
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-06
• Study Start: 2025-02-15
• Primary Completion: 2028-12-31
• Study Completion: 2028-12-31

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.
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. A confirmed ability to travel to one of the three sites where HBOT or sham can be administered.

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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. Pneumothorax
7. Poorly controlled seizure disorder
8. Chronic sinusitis
9. Chronic or acute otitis media
10. Major ear drum trauma.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hyperbaric oxygen therapy	Hyperbaric Oxygen therapy	HBOT GROUP will have HBOT with 100% oxygen for 90 min, once daily, five times a week for 8 consecutive weeks. This will be given at a slightly higher pressure than normal air pressure (2 times regular air pressure)
Hyperbaric oxygen sham	Hyperbaric Oxygen therapy	CONTROL GROUP will have sham treatment, which will look and feel like HBOT, but will not have high enough oxygen concentration for any therapeutic or health benefit. Sham treatment with 21% oxygen (the amount of oxygen normally present in the air) for 90 min, once daily, five times a week for 8 consecutive weeks. This will be given at standard atmospheric pressure (1.03 ATA). The air pressure will vary slightly to mimic the feeling of HBOT.

Primary Outcome Measures

Name	Time	Method
Simple reaction time [SRT] task from the TestMyBrain (TMB) Digital Neuropsychology Toolkit	Baseline/Start of intervention to two months	On-line survey tool
Verbal paired associates [VPA] task from the TestMyBrain (TMB) Digital Neuropsychology Toolkit	Baseline/Start of intervention to two months	On-line survey tool

Secondary Outcome Measures

Name	Time	Method
The Fatigue Scale	Baseline/start of intervention to 1, 2 months 3 and 6 months	The Fatigue Scale was adapted from the De Paul Symptom Questionnaire (DSQ2)'s 38 questions assessing medical history of Myalgic Encephalitis/Chronic Fatigue Syndrome (ME/CFS), comorbidities, medications, impact on quality of life and daily activities, etc.
Brief Fatigue inventory	Baseline/start of intervention to 1, 2 months 3 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.
Mental Health - General Anxiety Assessment Form (GAD-7)	Baseline/start of intervention to 1, 2 months 3 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 1, 2 months 3 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 1V (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.
Symptom Checklist	Baseline/start of intervention to 1, 2 months 3 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 CRF and the Symptom Burden Questionnaire for Long COVID): to track symptom trajectory.
SF-36	Baseline/start of intervention to 1, 2 months 3 and 6 months	The self-administered SF-36 evaluates eight health concepts: physical functioning, role functioning-physical, bodily pain, general health, vitality, social functioning, role functioning-emotional, and mental health. Previous studies have used this instrument in many different populations and it takes approximately 15 minutes to complete.
Post COVID19 functional status scale	Baseline/start of intervention to 1, 2 months 3 and 6 months	The post-COVID-19 functional status (PCFS) scale focuses on relevant aspects of daily life during follow-up after the infection. The scale is intended to help users become aware of current functional limitations in COVID-19 patients, whether or not as a result of the specific infection, and to objectively determine this degree of disability. The scale is ordinal, has 6 steps ranging from 0 (no symptoms) to 5 (death), and covers the entire range of functional outcomes by focusing on limitations in usual duties/activities either at home or at work/study, as well as changes in lifestyle. The PCFS demonstrates good construct validity.
Symptoms scale	Baseline/start of intervention weekly to 2 months, then once monthly to 6 months.	Three point Likert scale assessing how bothersome symptoms are on a weekly basis for two months then monthly until end of study, as reported by the participant: to provide a granular, detailed picture of the symptom trajectory.
Six Minute Walking Test (6MWT) with oximetry	Baseline/start of intervention and 2 months.	Subjects walk as far as they can in six minutes while receiving maximum encouragement. It is simple to execute, inexpensive, standardized and gives a tangible measure of functional exercise capacity. It has been validated in many different populations. The 6MWT will be conducted according to American Thoracic Society standards.
Reintegration to Normal Living Index (RNLI)	Baseline/start of intervention to 1, 2 months 3 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.
TestMyBrain cognitive testing	Baseline/start of intervention to 1, 2 months 3 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 includes: TMB Verbal Paired Associates (Concrete), TMB Digit Span - Backward, TMB Digit Span - Forward, TMB Choice Reaction Time, TMB Simple Reaction Time, TMB Gradual Onset Continuous Performance Task. The 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.
Dyspnea	Baseline/start of intervention to 1, 2 months 3 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.
Post-Exertional Malaise	Baseline/start of intervention to 1, 2 months 3 and 6 months	The self-administered DPEMQ is comprised of three sections assessing post-exertional malaise (PEM): (i) onset and triggers of PEM (9 questions), (ii) consequences and symptoms (14 questions), (iii) duration, recovery and pacing (7 questions).
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