- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04647656
Hyperbaric Oxygen Therapy for Post-COVID-19 Syndrome (HBOTpCOVID)
Hyperbaric Oxygen Therapy for Post-COVID-19 Syndrome: a Prospective, Randomized, Double Blind Study.
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Zerifin, Israel, 70300
- Assaf-Harofeh Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age above 18 years
- Reported post COVID-19 cognitive deterioration that effect quality of life and persist at least 3 months after confirmed infection.
- Subject willing and able to read, understand and sign an informed consent
Exclusion Criteria:
- Inability to attend scheduled clinic visits and/or comply with the study protocol
- History of traumatic brain injury (TBI) or any other non COVID brain pathology
- Active malignancy
- Substance use at baseline
- Severe or unstable physical disorders or major cognitive deficits at baseline
- HBOT for any reason prior to study enrolment
- Chest pathology incompatible with pressure changes (including moderate to severe asthma)
- Ear or Sinus pathology incompatible with pressure changes
- An inability to perform an awake brain MRI
- Active smoking
Study Plan
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
Sponsor
Publications and helpful links
General Publications
- Carfi A, Bernabei R, Landi F; Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020 Aug 11;324(6):603-605. doi: 10.1001/jama.2020.12603.
- Garrigues E, Janvier P, Kherabi Y, Le Bot A, Hamon A, Gouze H, Doucet L, Berkani S, Oliosi E, Mallart E, Corre F, Zarrouk V, Moyer JD, Galy A, Honsel V, Fantin B, Nguyen Y. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J Infect. 2020 Dec;81(6):e4-e6. doi: 10.1016/j.jinf.2020.08.029. Epub 2020 Aug 25.
- Boussi-Gross R, Golan H, Fishlev G, Bechor Y, Volkov O, Bergan J, Friedman M, Hoofien D, Shlamkovitch N, Ben-Jacob E, Efrati S. Hyperbaric oxygen therapy can improve post concussion syndrome years after mild traumatic brain injury - randomized prospective trial. PLoS One. 2013 Nov 15;8(11):e79995. doi: 10.1371/journal.pone.0079995. eCollection 2013.
- Stam HJ, Stucki G, Bickenbach J; European Academy of Rehabilitation Medicine. Covid-19 and Post Intensive Care Syndrome: A Call for Action. J Rehabil Med. 2020 Apr 15;52(4):jrm00044. doi: 10.2340/16501977-2677.
- Tal S, Hadanny A, Berkovitz N, Sasson E, Ben-Jacob E, Efrati S. Hyperbaric oxygen may induce angiogenesis in patients suffering from prolonged post-concussion syndrome due to traumatic brain injury. Restor Neurol Neurosci. 2015;33(6):943-51. doi: 10.3233/RNN-150585.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Coronavirus Infections
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Pneumonia, Viral
- Pneumonia
- Lung Diseases
- Neurocognitive Disorders
- Cognition Disorders
- COVID-19
- Cognitive Dysfunction
Other Study ID Numbers
- 332-20-ASF
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
Clinical Trials on Covid19
-
Anavasi DiagnosticsNot yet recruiting
-
Ain Shams UniversityRecruiting
-
Israel Institute for Biological Research (IIBR)Completed
-
Colgate PalmoliveCompleted
-
Christian von BuchwaldCompleted
-
Luye Pharma Group Ltd.Shandong Boan Biotechnology Co., LtdActive, not recruiting
-
University of ZurichLabor Speiz; Swiss Armed Forces; Universitätsspital ZürichEnrolling by invitation
-
Alexandria UniversityCompleted
-
Erasmus Medical CenterUniversity Medical Center Groningen; Academisch Medisch Centrum - Universiteit... and other collaboratorsRecruiting
Clinical Trials on Hyperbaric oxygen
-
National Baromedical ServicesMayo Clinic; Dartmouth-Hitchcock Medical Center; Eastern Virginia Medical School and other collaboratorsCompletedCarcinoma, Squamous Cell | Cancer of the Head and NeckUnited States
-
Bayside HealthNational Health and Medical Research Council, Australia; Monash UniversityCompletedTibial Fracture | Soft Tissue InjuryAustralia, Sweden, Chile, United States, Austria, India, Italy, Portugal, Czechia
-
Louisiana State University Health Sciences Center...U.S. Army Medical Research and Development CommandUnknownTraumatic Brain Injury | Post-Concussion SyndromeUnited States
-
Hull University Teaching Hospitals NHS TrustNorth of England Medical & Hyperbaric ServicesCompletedMyocardial Reperfusion Injury | CytoprotectionUnited Kingdom
-
Stanford UniversityRecruiting
-
Erasmus Medical CenterDa Vinci Clinic; HGC RijswijkNot yet recruitingPost-COVID-19 Syndrome | Long COVID | Long Covid19 | Post COVID-19 Condition | Post-COVID Syndrome | Post COVID-19 Condition, Unspecified | Post-COVID ConditionNetherlands
-
Omar AljitawiCompleted
-
University of British ColumbiaUnknown
-
U.S. Army Medical Research and Development CommandCompletedTraumatic Brain Injury | Post-concussive SymptomsUnited States
-
St. Joseph's Healthcare HamiltonUniversity Health Network, Toronto; Judy Dan Research and Treatment Centre...CompletedDiabetes Mellitus | Chronic Ulcers of the Lower LimbCanada