Description

Study Protocol Summary:

Long-term effect of hyperbaric oxygen therapy on cognitive functions in patients after traumatic brain injury

Study number: 0172-21-ASF Protocol number: 0172-21-ASF Protocol date: July 12, 2021 Protocol version: 1.0 Study type: No investigational product

Purpose of the trial, rationale including definition of quantitative measures and description of participant recruitment:

Background and rationale:

Traumatic brain injury (TBI) is one of the most common causes of disability and death in the general population \[1\]. Recent studies have shown that hyperbaric oxygen therapy helps improve cognitive function and quality of life in patients with chronic neurological deficits after traumatic brain injury of various severities, due to changes in brain neuroplasticity \[2-4\]. To date, only a few studies have examined the sustained effect of hyperbaric therapy on somatic, cognitive, or emotional symptoms in this population. Only two studies examined persistent effects in the range of 6 to 12 months after the end of a series of treatments \[5-6\].

Study objective:

The aim of the current study is to evaluate the cognitive functions of patients who suffered brain injury due to traumatic head injury and were previously treated in a hyperbaric chamber between one and four years after the end of treatment.

Participant recruitment procedure:

Participants who were treated with a series of hyperbaric chamber treatments at Shamir Medical Center between 2017 and 2021 will be identified. Patients will be invited by telephone to participate in the study; those who agree will be summoned to the Sagol Center, will sign an informed consent form, and will undergo a cognitive assessment.

Detailed study plan and clinical follow-up (during and after treatment):

Eligible participants will be invited for an assessment visit that will include: signing the informed consent form, self-completion of validated computerized questionnaires, and a computerized cognitive assessment test. In addition, cognitive assessment results performed before and after the hyperbaric treatment series will be extracted from the patients' medical records, as well as demographic data, comorbidities, type and severity of the injury, time since the event, symptoms and changes reported during the hyperbaric treatment.

Outcome assessment:

Study outcomes will be evaluated by examining the following parameters:

Cognitive functions: memory, processing speed, attention and executive functions will be assessed using Neurotrax software and the CANTAB battery.

Quality of life measures: using the SF-36 (The Short Form 36 Health Survey Questionnaire).

Post-concussion symptoms following traumatic brain injury: using the BC-PSI (British Columbia Postconcussion Symptom Inventory).

Statistical analysis:

Continuous data with normal distribution will be presented as mean ± standard deviation. Continuous data that are not normally distributed will be reported as median and interquartile range. Categorical data will be presented as proportions. Unpaired t-tests will be used to compare continuous data between two groups; Chi-Square/Fisher's Exact tests will be used to compare categorical data. The longitudinal effect of the treatment will be examined using repeated measures ANOVA, with multiple-comparison correction performed using the FDR (false discovery rate) test. A p-value below 0.05 will be considered statistically significant. Statistical analysis will be performed using Matlab Version 2020b.

Number of participants at this center:

100

Age range:

Over 18 years

Sex

Women and men

Inclusion criteria (main):

Subjects who were over 18 years old at the time of hyperbaric treatment. Subjects with chronic neurological deficits after traumatic brain injury of any severity who received hyperbaric chamber treatment.

Completed a series of at least 50 hyperbaric chamber treatments at Shamir Medical Center and underwent two computerized cognitive tests (before and after the treatment series).

Exclusion criteria (main):

Inability to perform a computerized cognitive test. A subsequent head injury or stroke after completion of the hyperbaric treatment series.

Known history of psychiatric illness. Active malignancy. Use of illicit substances or medications that affect cognitive function. Inability to sign informed consent.

Criteria for withdrawal from the study:

Noncompliance with the protocol

Consideration of inclusion of pregnant women, special populations-children and those lacking decision-making capacity (including ethical aspects, benefits to participants versus risks and discomfort):

Not included

Duration of treatment per participant and total study duration including post-study follow-up:

12 months

References

1. Coronado VG, Xu L, Basavaraju SV, McGuire LC, Wald MM, et al. Surveillance for traumatic brain injury-related deaths; United States, 1997-2007.
2. Tal S, Hadanny A, Berkovitz N, Sasson E, Ben-Jacob E, et al. (2015) Hyperbaric oxygen may induce angiogenesis in patients suffering from prolonged post-concussion syndrome due to traumatic brain injury. Restor Neurol Neurosci 33: 943-951.
3. Boussi-Gross R, Golan H, Fishlev G, Bechor Y, Volkov O, et al. (2013) Hyperbaric oxygen therapy can improve post concussion syndrome years after mild traumatic brain injury - randomized prospective trial. PLoS One 8: e79995.
4. Hadanny A, Rittblat M, Bitterman M, May-Raz I, Suzin G, et al. (2020) Hyperbaric oxygen therapy improves neurocognitive functions of post-stroke patients - a retrospective analysis. Restor Neurol Neurosci 38: 93-107.
5. Lin J-W, Tsai J-T, Lee L-M, Lin C-M, Hung C-C, et al. (2008) Effect of hyperbaric oxygen on patients with traumatic brain injury. Reconstructive Neurosurgery: Springer. pp. 145-149.
6. Deru K, Price RC, Williams CS, Orrison WW, Walker JM, et al. (2018) Hyperbaric oxygen for post-concussive symptoms in United States military service members: a randomized clinical trial.