Hyperbaric Oxygen Therapy for Adult Onset Post Traumatic Stress Disorder
Description:
Posttraumatic stress disorder (PTSD) has been described as "the complex somatic, cognitive,
affective, and behavioral effects of psychological trauma". PTSD is triggered by a severe
distressing traumatic event, in which an overwhelming amount of stress exceeds the ability of
the individual to cope or integrate the emotions involved in the experience. The fact that a
large portion of the affected population is previously healthy, young people who were thrown
off their life course, contribute to the great motivation for research in this field. But
unfortunately, the current available treatment improve some of the symptoms in only 32-66% of
patients, and even after treatment, up to 60% still meet PTSD diagnosis.
In the last few years, there is growing knowledge regarding the neuro-biological changes that
characterize PTSD. Brain imaging demonstrates alterations in regional brain perfusion, with
stunning, hypoperfused regions. Those enduring brain-biological pathologies may explain the
limited success rate of currently available interventions.
Accumulating studies presents evidence that hyperbaric oxygen therapy (HBOT) can induce
neuroplasticity and recovery of metabolic injured brain tissues, even years after the acute
insults. HBOT can initiate several brain-repair related mechanisms including brain
angiogenesis; improve cerebral vascular flow enable regeneration of axonal white matter,
stimulate axonal growth, promote blood-brain barrier integrity and reduce inflammatory
reactions, as well as in brain edema.
The potential beneficial effects of HBOT were demonstrated in several clinical trials of
traumatic brain injury(TBI)/post-concussion patients. Some of these trials, especially those
in veterans, included patients who, in addition to post-concussion syndrome, had PTSD; as it
is estimated that half of the soldiers with post-concussion syndrome due to mild TBI also
meet the criteria of PTSD.
The aim of the proposed study is to evaluate the effect of HBOT on PTSD symptoms in adults
with treatment resistant PTSD who were not exposed to TBI or blast injury. In addition to the
clinical outcome, brain functionality and microstructure will also be evaluated by PET and
DTI-MRI in order to shed additional light on the pathophysiology of PTSD and its response to
treatment.
Study protocol:
Thirty male patients with adult onset PTSD, defined by DSM-V criteria, as a result of combat
or a terror- related event, will be recruited to the study. Further criteria for study
inclusion will be: age 25-60 years, 4-years or more from the traumatic event and failure to
improve with at least one line of conventional treatment.
Study exclusion criteria will be: a history of traumatic brain injury or blast injury,
epilepsy, a brain tumor; skull base fractures or neurosurgery, severe substance use
disorders, a current manic episode, psychotic disorders or serious suicidal ideation at
baseline; or major cognitive deficits; a history of HBOT for any reason prior to study
enrollment; chest pathology incompatible with pressure changes (including active asthma);
inner ear disease; the inability to perform an awake brain MRI test; and the inability to
provide informed consent.
After recruitment, participants will be randomized to one of two study groups . A treatment
group will proceed to a course of HBOT, while participants in the control group will continue
with the current standard of care of psychiatric support and medications. After 3 months of
follow up, participants of both groups will be re-evaluated. The individuals in the control
group will then be offered to receive the treatment and to be re-reevaluated after the
treatment is over (3 months). Further evaluation will be done at 6 and 12 month to evaluate
long term effects of the treatment. During the study, all participant will continue with
their current medications unless otherwise advise by their treating physician.
According to the HBOT protocol, 60 daily HBOT sessions will be administrated 5 days per week.
Comprise of 90 minutes exposure to 100% oxygen at 2 ATA, with 5-minute air breaks every 20
minutes.
Study end points:
Primary end point PTSD symptoms, as assessed by the PTSD questionnaire
Secondary end points
1. Sleep disorders questionnaire: Medical Outcome Sleep Scale (MOS)
2. Quality of life and mood questionnaires: Patient global impression of change, SF-36,
EQ-5D, SCL51
3. Diary for daily documentation of symptoms
4. Cognitive function- Cognitive function will be evaluated by the mainstreams Cognitive
Health Assessment.
5. Brain imaging Brain imaging will include 2 types of imaging: perfusion magnetic
resonance imaging (MRI) + diffusion tensor imaging (DTI), including resting state
functional MRI and brain single photon emission computed tomography (PET-CT).
5.1 Perfusion MRI+DTI and Resting state fMRI (rsfMRI) a method of functional brain
imaging that can be used to evaluate regional interactions that occur when a participant
is not performing an explicit task. This resting brain activity is observed by means of
changes in blood flow in the brain, which creates what is referred to as a
blood-oxygen-level dependent (BOLD) signal that can be measured using functional MRI
(fMRI). +task 5.2 PET CT
6. Physiological evaluation of brain functionality using transcranial magnetic stimulation
(TMS)-EEG examination:
This examination includes non-invasive safe brain monitoring and stimulation for the
assessment of changes in brain functionality and connectivity. The procedure includes
placement of EEG electrodes on an individual’s head and measurement of the TMS-evoked
electrophysiological response in the various brain regions. The examination takes about 30
minutes.
Condition:
Ptsd
Treatment:
Hyperbaric oxygen-90 minutes exposure to 100% oxygen at 2 ATA, with 5-minute air breaks every 20 minutes
Start Date:
March 4, 2018
Sponsor:
Assaf-Harofeh Medical Center
For More Information:
https://clinicaltrials.gov/show/NCT03466554