Clinical trial NCT01729780: Early EEG-NF Intervention for the Prevention of PTSD
Official title: Early EEG-NF Intervention for the Prevention of PTSD in First Time ACS Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: PTSD
Acute Coronary Syndrome
Keywords: EEG-NF
Neurofeedback
Prevention
ACS
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
First posted: 2012-11-20
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 12% of patients suffering from an acute crornary syndrome will develop long lasting anxiety symptoms. The object of this study is to lessen or prevent these symptoms by the use of neurofeed back (EEG-NF).

Detailed description: The accepted definition for a mentally traumatic event is an event in which there is a chance of death, severe injury or a severe threat to one's body (either as a victim or as an observer) and that event stimulates an intense emotional response of fear, horror or helplessness1. About forty percent of western population will undergo such an event during their life time, out of which up to thirty percent will suffer from a short live anxiety disorder and up to quarter will suffer from a chronic anxiety disorder (PTSD - Post Traumatic Stress Disorder) or depression2,3.

The distinction between different anxiety disorders is based on their time of appearance and how long they will last. The shortest disorder is the acute stress reaction (ASR) which appears immediately after the traumatic event and will disappear after 48 - 72 hours. ASR symptoms include dissociation, anxiety and affective instubility3. The medium range anxiety disorder is the acute stress disorder (ASD), which appears in the first two weeks following the event and will last up to a month. Its symptoms include dissociation, re-experiencing of the traumatic event and avoidant behavior of places and actions that might resemble the traumatic event. The long lasting disorder is the post traumatic stress disorder (PTSD), which lasts more than a month and includes symptoms of re-experiencing, avoidant behavior and hyper arousal1.

A recent meta analysis of studies on the prevalence of PTSD in patients suffering from an acute coronary syndrome (ACS) demonstrated that about 12% will develop PTSD (in some studies the prevalence was up to 32%). In three of the studies that were included, the morbidity and mortality stemming from the PTSD were examined and were twice as high compared to the patients without PTSD4.

The personal, social and financial toll of anxiety disorders is significant and still, to date, there is no excepted treatment that aims to prevent the occurrence of these disorders. A few studies on the subject have shown that early interventions (done in the days to weeks after the traumatic event) have an advantage in the prevention of PTSD, as opposed to immediate interventions (that show no benefit)5,6.

Due to the subjectivity of the experience of a traumatic event there is great difficulty in the prediction of who will develop an anxiety disorder. A few risk factors for the development of PTSD were suggested in different studies: female sex, minors, low socioeconomic status, young age, history of trauma, mental illness, little social support, the severity of the event and adrenergic hyperactivity following the event5.

The brain areas that were reported as being involved in PTSD are the Amygdala and the prefrontal cortex7. Still, these observations are not enough to construct a predictive model that will allow diagnosis and / or treatment. A prospective study, done in our lab, demonstrated hyperactivity in the Amygdala alongside changes in hypocampal plasticity and a decrease in the activity of the ventromedial prefrontal cortex in comparison to baseline in subjects suffering from PTSD, or that have shown high levels of anxiety without a formal diagnosis of an anxiety disorder8.

Pharmacological interventions after trauma events have shown poor specificity and benefit. In contrast, behavioral \\ psychological interventions such as cognitive behavioral therapy (CBT) that are trauma oriented have shown some benefit6. Alas, due to their nature of re-experiencing and reliving of the traumatic events patients are reluctant to partake.

A new kind of intervention, that has been becoming popular in the past few years, is changing of brain wave pattern by the use of Neurofeedback (EEG-NF). By using a closed circuit brain computer interface (BCI), the patient receives feedback about his (or hers) brain activity via an external marker that is linked to his mental status. The feedback allows the patient modulation of brain activity in a designated area to which the practice is aimed. The practice lasts a few sessions, after which the patient can apply the technique without immediate feedback10,11.

Early studies of EEG-NF focused on alpha waves (8 - 12 Hz) due to their link to feelings for calm12,13. Later, the method was broadened due to findings that showed that during a state of sleepiness the main frequency in brain activity is low theta waves (4-7 Hz)14. The method of A/T NF was since used in the research and in treatment of ADD/ADHD15 and was shown to be useful in the alleviation of symptoms of PTSD in two studies16,17. In a recent study EEG-NF was effective in reducing level of anxiety in patients after an acute coronary event18.

First appointment - Subjects will be asked to join during their hospitalization in the cardiac intensive care unit at the first 72 hours after their coronary event. In this meeting subjects will be asked to sign an informed consent form and will be interviewed by one of the study team members and will be asked to answer psychological questioners. Also, they will perform a resting EEG, while trying to relax with no special guidance. The meeting will last about an hour.

Some of the subjects will be asked to undergo an MRI brain scan during that hospitalization. In the first part of the scan subjects will be asked to remain still for a few moments and try to relax (with no special guidance). After that they will watch a series of pictures and movie clips with emotional valence. During the final part of the scan subjects will be asked again to remain still for a few moments. This meeting, when performed, will also last for about an hour.

First follow up meeting (will be done face to face or by phone): A month following the coronary event a team member will contact the subjects and ask for a second appointment, during which the questioners will be redone in order to asses anxiety and depression levels, including the appearance of post traumatic symptoms. The purpose of this meeting is to identify the subject at high risk for developing PTSD. The meeting will last about an hour.

After the second meeting sixty patients, who exhibited post traumatic symptoms, will be asked to continue in the study. The rest will be excluded from it. Those who will continue will undergo 12 additional meetings:

An initial meeting before starting the EEG-NF training, during which patients will fill questioners and will undergo resting EEG with no guidance. After which they will undergo an MRI scan during rest and exposure to stimuli. This meeting will last an hour and a half to two hours.

Next, the subjects will be divided into two groups. The first will undergo ten EEG-NF training meetings and the second will undergo ten shame EEG-NF meetings. The meetings will be done in a time frame of two months and will be guided by the study's team members.

The EEG-NF training will be alpha/theta EEG, as specified earlier. Each subject will be connected to an EEG device continuously registering his / hers' brainwave activity. The alpha/theta ratio will be computed online and will be translated to the subject as a sound. A decrease in the ration, implicating relaxation, will lead to a decrease in the sounds' volume. The subject will be asked to continue and soften the sound by relaxing. Each meeting will last twenty minutes.

The shame group will be connected to the same EEG device, will hear the same sound and will be asked to relax in order to soften the sound. The sounds' volume will not be depended on their alpha/theta ratio and will change randomly. Each meeting will last twenty minutes.

Final meeting: two to four weeks following the completion of the ten EEG-NF meetings (true or shame), subjects will be asked for a final meeting in which they will undergo clinical evaluation and a second MRI brain scan. They will fill the same questioners as earlier. This meeting will last an hour and a half to two hours.

Eligibility criteria: Inclusion Criteria:

* First ACS.
* Hemodynamic stable.
* Underwent MRI scan clearance as accustomed in the Tel Aviv medical center.
* The participation of a patient, who underwent an insertion of a coronary stent, will be allowed only if the stent maker cleared in writing the stent exposure to a magnetic field of 3 Tesla, and a written consent by the patients' cardiologist was supplied

Exclusion Criteria:

* Patient does not speak Hebrew.
* The patient is having chest pain.
* History of psychiatric or neurologic condition requiring hospitalization.
* Hemodynamic instability.

Primary outcomes:
measure: Anxiety levels after 10 sessions of EEG-NF.
timeFrame: 2 to 4 weeks after complition of the meetings.
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: The center for brain functions research, Tel Aviv medical center.
name: Talma - Hendler, Prof'
role: PRINCIPAL_INVESTIGATOR
References:
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