Hyperbaric Oxygen Therapy for Post-COVID-19 Syndrome (HBOTpCOVID)
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|ClinicalTrials.gov Identifier: NCT04647656|
Recruitment Status : Not yet recruiting
First Posted : December 1, 2020
Last Update Posted : December 1, 2020
|Condition or disease||Intervention/treatment||Phase|
|Covid19 Neurocognitive Dysfunction||Device: Hyperbaric oxygen Device: Sham||Not Applicable|
Post-COVID-19 syndrome is an assembly of signs and symptoms first described on patients recovering from severe 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 serries 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 . 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 IL-1, IL-6, 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 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 (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Hyperbaric Oxygen Therapy for Post-COVID-19 Syndrome: a Prospective, Randomized, Double Blind Study.|
|Estimated Study Start Date :||January 1, 2021|
|Estimated Primary Completion Date :||January 1, 2022|
|Estimated Study Completion Date :||January 1, 2023|
Active Comparator: HBOT treatment group
40 daily hyperbaric oxygen treatment sessions will be administered 5 days per week
Device: Hyperbaric oxygen
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
- Cognitive health assessment (NeuroTrax) [ Time Frame: Baseline, 2 months ]Memory, attention and information process will be evaluated using the NeuroTrax computerized cognitive evaluation battery.
- Brain perfusion [ Time Frame: Baseline, 2 months ]Cerebral blood volume and flow will be measured using perfusion MRI protocol Dynamic susceptibility contrast (DSC).
- 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
- 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
- Post-COVID-19 symptom [ Time Frame: Baseline, 2 months ]Self-reported questionnaire covers the most common symptoms related to post-COVID19 disease
- Quality of Life SF-36 [ Time Frame: Baseline, 2 months ]SF-36 questionnaire for self reporting qulity of life
- The Pittsburgh Sleep Quality Index PSQI [ Time Frame: Baseline, 2 months ]The Pittsburgh Sleep Quality Index (PSQI) is a self-report questionnaire that assesses sleep quality
- The Brief Symptom Inventory - 18 (BSI-18) [ Time Frame: Baseline, 2 months ]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
- BPI - Brief pain inventory (short form) [ Time Frame: Baseline, 2 months ]The 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.
- 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).
- Neurological evaluation [ Time Frame: Baseline, 2 months ]The neurological exam will include tests of the cranial nerves, motor, sensory and cerebellar function and gait
- 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 (Sniffin' 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").
- 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.
- Echocardiography [ Time Frame: Baseline, 2 months ]Conventional echocardiography evaluation, linear, volumetric and Doppler measurements will be performed to assess cardiac functions.
- Lung functions test [ Time Frame: Baseline, 2 months ]Measurements of pulmonary functions will be performed using the MiniSpir testing apparatus.
- Immune system [ Time Frame: Baseline, 2 months ]Blood tests will evaluate immune system including cytokines, CRP and COVID-19 antibodies
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04647656
|Contact: Shani Zilberman-Itskovich, Dr.||firstname.lastname@example.org|
|Contact: Shai Efrati, Prof.||email@example.com|
|Assaf-Harofeh medical center|
|Zerifin, Israel, 70300|
|Contact: Shani Zilberman-Itskovich, Dr. +97289979383 firstname.lastname@example.org|