The Role of Hyperbaric Oxygen and Neuropsychological Therapy in Cognitive Function Following Traumatic Brain Injury

NCT03900182 | Terminated DMC

• 1 other identifier: 201801854A3
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Traumatic brain injury (TBI) caused by accidents is a very important public health problem in Taiwan. There are many people with brain damage and cognitive dysfunction caused by traumatic brain injury every year. Currently, there is no effective treatment for cognitive dysfunction caused by traumatic brain injury. Evidence from clinical studies in recent years suggests that hyperbaric oxygen therapy may be a treatment for repairing nerves after brain injury. Many studies have shown that oxidative stress and inflammatory responses play an important role in the pathogenesis of the central nervous system. In recent years, our research team has shown that oxidative stress and inflammatory response are significantly associated with the prognosis of patients with traumatic brain injury, cerebral hemorrhage, and stroke patients. More and more evidences also show that oxidative stress and inflammatory response play an important role in the neuropathological changes of mental cognitive sequelae after traumatic brain injury. This injury may be gradual from the time of head trauma. This process begins with the generation of oxidative stress and free radicals. When the cell repair and free radical scavenging system can not effectively overcome the excessive production of free radicals, an oxidative damage reaction will occur, causing a series of inflammatory cells and cytokines to be activated. Studies have also shown that when inhibiting those free radicals that produce oxidative stress, the neurological function and cognitive function of the head after trauma can be significantly improved. It is becoming widely acknowledged that the combined action of hyperoxia and hyperbaric pressure leads to significant improvement in tissue oxygenation while targeting both oxygenand pressure-sensitive genes, resulting in improved mitochondrial metabolism with anti-apoptotic and anti-inflammatory effects. The investigators published an article this year showing that hyperbaric oxygen therapy can improve the prognosis of patients with acute stroke and increase endothelial progenitor cells in the systemic circulation. The investigators plan to conduct this research project through hyperbaric oxygen therapy and neuropsychological therapy, and using scientific tests and neurocognitive function assessments. The investigators hope to answer the following questions: (1) Whether the treatment of hyperbaric oxygen can improve oxidative stress and inflammatory response after brain injury, and observe changes in biomarker concentration; (2) Whether hyperbaric oxygen therapy and neuropsychological therapy can improve cognitive function after brain injury; and (3) which biomarkers are factors that influence cognitive function prognosis.

Conditions

Brain Injuries, Traumatic; Neuropsychology

Keywords

Traumatic brain injury; hyperbaric oxygen therapy; neuropsychological treatment; cognitive function; biomarkers.

Outcome Measures

Primary Outcomes (6)

• Neuropsychological testing- Wechsler Adult Intelligence scale-III (WAIS-III)

  Subtests included the followings: Information with a measure of general knowledge, digit Span, vocabulary ability to define 35 words, arithmetic, comprehension, similarities, picture completion, picture arrangement, block design, digit symbol, and object assembly. The scores could further subscore into verbal comprehension, perceptual reasoning and working memory index.

  Change from baseline, at after 6 weeks of HBOT and at after 6 times of neuropsychological treatment.

• Neuropsychological testing- Cognitive Ability Screening Instrument (CASI)

  includes tests of nine domains of cognitive function (attention, concentration, orientation, short and long-term memory, language ability, visual construction, word list generation, abstraction, and judgment), and the score ranges from 0 (worst) to 100 (best score).

  Change from baseline, at after 6 weeks of HBOT and at after 6 times of neuropsychological treatment.

• Neuropsychological testing- mini-mental state examination (MMSE)

  The Mini-Mental State Examination (MMSE) test is a 30-point questionnaire. Any score greater than or equal to 24 points (out of 30) indicates a normal cognition. Below this, scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-23 points) cognitive impairment.

  Change from baseline, at after 6 weeks of HBOT and at after 6 times of neuropsychological treatment.

• Neuropsychological testing- Short Form 36 questionnaire

  The SF-36 taps eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Scoring the SF-36 is a two-step process. First, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are set at 0 and 100, respectively. Scores represent the percentage of total possible score achieved. In step 2, items in the same scale are averaged together to create the 8 scale scores.

  Change from baseline, at after 6 weeks of HBOT and at after 6 times of neuropsychological treatment.

• Neuropsychological testing- The World Health Organization Quality of Life questionnaire (WHOQOL-BREF)

  questionnaire is a 26-item questionnaire that evaluates 4 domains of quality of life (QoL), namely Physical, Psychological, Social Relationships and Environment

  Change from baseline, at after 6 weeks of HBOT and at after 6 times of neuropsychological treatment.

• Neuropsychological testing- Beck Depression Inventory

  The BDI-II contains 21 questions, each answer being scored on a scale value of 0 to 3. Higher total scores indicate more severe depressive symptoms. The standardized cutoffs used here differ from the original as such: 0-13: minimal depression; 14-19: mild depression; 20-28: moderate depression; and 29-63: severe depression.

  Change from baseline, at after 6 weeks of HBOT and at after 6 times of neuropsychological treatment.

Secondary Outcomes (17)

• oxidative damage markers: Erythrocyte superoxide dismutase (SOD) activity

  Change from baseline, at after 6 weeks of HBOT and at after 6 times of neuropsychological treatment.

• oxidative damage markers: Erythrocyte glutathione peroxidase (GPx) activity

  Change from baseline, at after 6 weeks of HBOT and at after 6 times of neuropsychological treatment.

• oxidative damage markers: serum malondialdehyde (MDA) content

  Change from baseline, at after 6 weeks of HBOT and at after 6 times of neuropsychological treatment.

• oxidative damage markers: serum free thiol content

  Change from baseline, at after 6 weeks of HBOT and at after 6 times of neuropsychological treatment.

• Cytokines (IL-1β) by Enzyme-linked immunosorbent assays

  Change from baseline, at after 6 weeks of HBOT and at after 6 times of neuropsychological treatment.

Study Arms (2)

HBO treated group

ACTIVE COMPARATOR

Patients in the treated group were evaluated three - at baseline, after 6 weeks of HBOT and after 6 weeks of neuropsychological treatment or no treatment.

Device: Hyperbaric Oxygen Therapy

crossover group

SHAM COMPARATOR

Patients in the crossover group were evaluated three times: baseline, after 6 weeks control period of no treatment, and after subsequent 6 weeks of HBOT

Device: Hyperbaric Oxygen Therapy

Interventions

Hyperbaric Oxygen Therapy DEVICE

The Hyperbaric Oxygen Therapy (HBOT) patients were placed in a chamber that was pressurized with air to 2.5 ATA during 15 min and were supplied 100% oxygen for 25 mins, followed by a 5-min air break. This cycle was repeated once and followed by 100% oxygen for 10 min, after which time the chamber was depressurized to 1 ATA over 15 min with 100% oxygen for a total treatment time of 100 min.

Also known as: Neuropsychological Therapy

HBO treated group; crossover group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Traumatic brain injury, mild and moderated.
• Age between 18 and 65 years old

You may not qualify if:

• Penetrating injury, including gunshot injury
• Combined with other major trauma which had unstable hemodynamics
• Major systemic disease, such ESRD, liver cirrhosis, CHF, or a malignant disease
• Evidence for alcoholism or any other addictive disorders, or known affective or other psychiatric disease or use of sedatives or neuroleptic medication
• Known neurological disorders potentially affecting the central nervous system or severe recent life events that might have interfered with neuropsychological testing.

Sponsors & Collaborators

• Hung-Chen Wang: lead

Study Sites (1)

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

Related Publications (38)

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MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Hyperbaric Oxygenation

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Oxygen Inhalation Therapy; Respiratory Therapy; Therapeutics

Study Officials

• Tsang-Tang Hsieh, MD

  Chang Gung Medical Foundation

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Attending physician; Associate professor

Model Details: After signing an informed consent form, the patients were invited for baseline evaluation. Included patients were randomized into two groups. The neuropsychological functions were the primary endpoints of the study. Secondary end point included quality of life evaluation. Evaluations were made by medical and neuropsychological practitioners who were blinded to patients' inclusion in the control-crossed or the treated groups. Patients in the treated group were evaluated three - at baseline, after 6 weeks of HBOT and after 6 weeks of neuropsychological treatment or no treatment. Patients in the crossover group were evaluated three times: baseline, after 6 weeks control period of no treatment, and after subsequent 6 weeks of HBOT. The post-HBOT neuropsycological evaluations were performed more than 1 week (1-2 weeks) after the end of the HBOT protocol. The following HBOT protocol was practiced: 30 daily sessions, 5 days/week, 60 minutes each, 100% oxygen at 1.5ATA.

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: April 2, 2019
• Study Start: April 9, 2019
• Primary Completion: February 28, 2021
• Study Completion: February 28, 2021
• Last Updated: August 2, 2021

Record last verified: 2021-07

Locations

TW (1)