Hyperbaric Oxygen Therapy for Post-COVID-19 Syndrome (HBOTpCOVID)

October 17, 2023 updated by: Assaf-Harofeh Medical Center

Hyperbaric Oxygen Therapy for Post-COVID-19 Syndrome: a Prospective, Randomized, Double Blind Study.

Post-COVID-19 syndrome is an assembly of symptoms, following an infection with Coronavirus disease 2019 (COVID-19). The syndrome is characterized by cognitive impairment, fatigue, sleep disorders, smell and taste disorders, pain and more. This long-term sequela can last for months after recovering from the virus, and no treatment is known to date. The aim of this study is to compare the effect of HBOT vs. Sham on post COVID-19 syndrome

Study Overview

Status

Completed

Detailed Description

Post-COVID-19 syndrome is an assembly of signs and symptoms first described on patients recovering from severe Coronavirus 2019 (COVID-19) infection. The syndrome is characterized by cognitive impairment, fatigue, and other neurologic symptoms. With time, and the growing understanding on this unique virus, there is cumulative case series reports on patients with mild to moderate disease, suffering from long standing post-COVID-19 syndrome. Taking in consideration, this pandemic is worldwide and still spreading, there's an urgent need for effective treatment for those patients who are suffering from the long standing, life debilitating, post-COVID-19 syndrome.

Neurologic signs and symptoms are common during hospitalization with COVID-19, with 42% of patients at onset of the disease and 82% during the course of the disease. Patients report mainly on myalgias, headaches, encephalopathy, dizziness, dysgeusia, and anosmia. After recovering from COVID-19, many patients continue to suffer from symptoms. Only 13% of the patients were completely free of symptoms after full resolution of the virus. The main symptom, reported by more than half the patients included cognitive impairment, fatigue and sleep disorders. A recent study analyzed data from 84,285 Individuals who recovered from suspected or confirmed COVID-19 showed reduced cognitive performance. This deficit scales with symptom severity and is evident amongst those without hospital treatment.

Two main biological sequelae of COVID-19 might play a role in the pathogenesis of this syndrome. The first is hypercoagulability state accompanies acute infection. This is characterized by increased risk of small and large vessel occlusion and is associated with increased mortality [9]. Neurologic complications might be a result of micro-infarcts in the central of peripheral nervous system; The second is an uncontrolled inflammatory response, called cytokines storm. This cytokine release is characterized by an increase in interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α and a change in macrophages population. Thus, COVID-19 can cause neuroinflammation, that might be prolonged and lead to signs of post-COVID-19 syndrome.

The Micro-infarcts and neuroinflammation are important causes of local hypoxia, and specifically neurological hypoxia. One of the options to reverse hypoxia, reduce neuroinflammation and induce neuroplasticity is hyperbaric oxygen therapy (HBOT).

Hyperbaric oxygen therapy (HBOT) includes the inhalation of 100% oxygen at pressures exceeding 1 atmosphere absolute, thus enhancing the amount of oxygen dissolved in the body tissues. During HBOT, the arterial O2 tension typically exceeds 2000 mmHg, and levels of 200-400 mmHg occur in tissues Even though many of the beneficial effects of HBOT can be explained by improvement of tissue oxygenation, it is now understood that the combined action of hyperoxia and hyperbaric pressure, triggers both oxygen and pressure sensitive genes, resulting in inducing regenerative processes including stem cells proliferation and mobilization with anti-apoptotic and anti-inflammatory factors.

The HBOT protocol will be administrated in a multi-place chamber. The protocol includes 40 daily sessions, 5 sessions per week for two months. Treatment group will subjected to 100% oxygen by mask at 2 atmosphere (ATA) for 90 minutes with 5 minute air breaks every 20 minutes. Sham group will be subjected to 21% oxygen by mast for 90 minutes, at 1.2 ATA during the first five minutes of the session with the noise of circulating air, and then decrease slowly during the next five minutes to 1.03 ATA.

Study Type

Interventional

Enrollment (Actual)

91

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Zerifin, Israel, 70300
        • Assaf-Harofeh Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age above 18 years
  2. Reported post COVID-19 cognitive deterioration that effect quality of life and persist at least 3 months after confirmed infection.
  3. Subject willing and able to read, understand and sign an informed consent

Exclusion Criteria:

  1. Inability to attend scheduled clinic visits and/or comply with the study protocol
  2. History of traumatic brain injury (TBI) or any other non COVID brain pathology
  3. Active malignancy
  4. Substance use at baseline
  5. Severe or unstable physical disorders or major cognitive deficits at baseline
  6. HBOT for any reason prior to study enrolment
  7. Chest pathology incompatible with pressure changes (including moderate to severe asthma)
  8. Ear or Sinus pathology incompatible with pressure changes
  9. An inability to perform an awake brain MRI
  10. Active smoking

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: HBOT treatment group
40 daily hyperbaric oxygen treatment sessions will be administered 5 days per week
Each session will include exposure of 90 minutes to 100% at 2 ATA, with 5 minutes air breaks every 20 minutes
Sham Comparator: HBOT sham group
40 daily Sham non-hyperbaric oxygen treatment will be administered 5 days per week
Each session will include exposure of 90 minutes to 21% at 1.2 ATA during the first five minutes of the session with the noise of circulating air, and then decrease slowly during the next five minutes to 1.03 ATA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cognitive health assessment (NeuroTrax)
Time Frame: Baseline, 2 months
Memory, attention and information process will be evaluated using the NeuroTrax computerized cognitive evaluation battery.
Baseline, 2 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain perfusion
Time Frame: Baseline, 2 months
Cerebral blood volume and flow will be measured using perfusion MRI protocol Dynamic susceptibility contrast (DSC).
Baseline, 2 months
Brain microstructure Brain microstructure
Time Frame: Baseline, 2 months
Fractional anisotropy (FA) and Mean diffusivity (MD) will be evaluated using diffusion tensor imaging (DTI) MRI protocol
Baseline, 2 months
Brain function imaging
Time Frame: Baseline, 2 months
Resting state fMRI (rsfMRI), and task based fmri will evaluate brain function during a working memory task
Baseline, 2 months
Post-COVID-19 symptom
Time Frame: Baseline, 2 months
Self-reported questionnaire covers the most common symptoms related to post-coronavirus 2019 (COVID-19) disease
Baseline, 2 months
Neuro-physical evaluation
Time Frame: Baseline, 2 months

Static balance will be assessed by the Balance Error Scoring System (BESS); Dynamic balance and risk of falling will be assessed by the Timed Up and Go test (TUG) and 10-meter walk (10MW).

Muscle function will be assessed by the sit to stand (STS) test for the leg strength and endurance and hand-held dynamometry (HHD) for the isometric grip strength.

The sub-maximal aerobic capacity and endurance will be assessed by the 6-minute walk test (6MWT).

Baseline, 2 months
Neurological evaluation
Time Frame: Baseline, 2 months
The neurological exam will include tests of the cranial nerves, motor, sensory and cerebellar function and gait
Baseline, 2 months
Smell and taste evaluations.
Time Frame: Baseline, 2 months

Smell will be tested through smell identification kits to test for odour detection, discrimination and threshold. The kit is standardized for age and gender, and available in different languages (Sniffing sticks).

Taste will be tested on bilateral anterior and posterior parts of the tongue by four tastes: bitter, sour, salt and sweet ("The Taste Strip Test").

Baseline, 2 months
Cardiopulmonary exercise test
Time Frame: Baseline, 2 months
The cardiopulmonary exercise test (CPET) is a non-invasive measurement of the cardiovascular system, respiratory system and muscles.
Baseline, 2 months
Echocardiography
Time Frame: Baseline, 2 months
Conventional echocardiography evaluation, linear, volumetric and Doppler measurements will be performed to assess cardiac functions.
Baseline, 2 months
Lung functions test
Time Frame: Baseline, 2 months
Measurements of pulmonary functions will be performed using spirometry (the MiniSpir) testing apparatus.
Baseline, 2 months
Immune system
Time Frame: Baseline, 2 months
Blood tests will evaluate immune system including cytokines, c-reactive protein (CRP) and COVID-19 antibodies
Baseline, 2 months
Quality of Life SF-36
Time Frame: Baseline, 2 months, 1 year
Short Form (SF)-36 questionnaire for self reporting quality of life
Baseline, 2 months, 1 year
The Pittsburgh Sleep Quality Index PSQI
Time Frame: Baseline, 2 months, 1 year
The Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality
Baseline, 2 months, 1 year
The Brief Symptom Inventory - 18 (BSI-18)
Time Frame: Baseline, 2 months, 1 year
The BSI-18 will be used to evaluate psychological distress. The BSI-18 is an 18 item self-report questionnaire which generates a summary scale, the global stress index (GSI), and three subscales: depression, anxiety, and somatization
Baseline, 2 months, 1 year
BPI - Brief pain inventory (short form)
Time Frame: Baseline, 2 months, 1 year
The Brief pain inventory (BPI) is a short, self-administered questionnaire. It contains 15 items, which include 2 multi-item scales measuring pain intensity and the impact of pain on functioning and well-being.
Baseline, 2 months, 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 14, 2020

Primary Completion (Actual)

December 27, 2021

Study Completion (Actual)

January 10, 2022

Study Registration Dates

First Submitted

November 29, 2020

First Submitted That Met QC Criteria

November 29, 2020

First Posted (Actual)

December 1, 2020

Study Record Updates

Last Update Posted (Actual)

October 18, 2023

Last Update Submitted That Met QC Criteria

October 17, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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