Estradiol-mediated Neural Plasticity as Potential Mediator of Neurofeedback Treatment Change for Traumatized Women

Post-traumatic stress disorder (PTSD) is a common debilitating disorder that affects many individuals exposed to aversive events. The severity of PTSD symptoms is positively correlated with amygdala activation. More severe PTSD symptoms following exposure to stressful events, are associated with amygdala hyper-responsivity prior to exposure. A possible intervention for PTSD is Neurofeedback (NF) - a treatment method based on learned self-modulation of neural activity in response to feedback of neural signal. Previous work in our lab established a NF training procedure that utilizes the temporal abilities of EEG with the spatial advantages of fMRI. Further work based on this method using the amygdala BOLD signal (EEG-finger-print, EFP) has demonstrated a potential for improving the ability to self-regulate amygdala activity and to improve emotional regulation in a healthy population. The current study aims to investigate the potential of this method as a therapeutic intervention for PTSD among women with a history of childhood sexual abuse (CSA).

Study Overview

• Status: Unknown
• Conditions: Posttraumatic Stress Disorder (PTSD)
• Intervention / Treatment: Device: EFP-NF training

Detailed Description

Pretreatment phase- All participants will undergo clinician evaluation, self-report measures and emotional regulation tasks in TASMC. In addition, participants will undergo a functional and structural MRI to characterize brain network responses associated with emotional arousal and regulation.

Participants will be randomized to one of two arms: (1) NF-EFP group and treatment as usual at out-patient clinic (TAU) or (2) TAU (without EFP-NF). If participant has a steady menstrual cycle she will be randomized to one of three arms: (1) NF group administered during low estrogen phase (and maintain TAU); (2) NF group administered during high estrogen phase (and maintain TAU) or (3) TAU (without EFP-NF).

Treatment phase (10 weeks) EFP-NF training, twice a week for a total of 10 sessions. For participants with steady menstrual phase treatment will be administered NF during designated-estrogen phases (high or low).

Treatment as usual: Participants will obtain their regular treatment regimen (pharmacological and psychological) and meet with a psychologist/psychiatrist following the common practice in the clinic.

NF-EFP sessions: For the duration of each NF-EFP session the participant will be seated comfortably in front of a computer screen. A staff member will explain the goal of the meeting to the participant, present the equipment to be used and describe the course of the meeting. The EEG-NF practice will consist of four-minute segments repeated for up to 30 minutes. During each practice segment the participant will be asked to modify visual media that provides feedback on the degree of successful brain training. The duration of one session is approximately 45 minutes.

Post treatment phase -All participants will undergo clinician evaluation, self-report measures and emotional regulation tasks in TASMC. In addition, participants will undergo a functional and structural MRI to characterize brain network responses associated with emotional arousal and regulation.

Follow up- participants will be monitored by self-evaluation questionnaires post treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Tel Aviv, Israel
    • Recruiting
    • Tel Aviv Sourasky Medical Center Tel Aviv, Israel
    • Contact: Marina Gordon, BA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 62 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Women of age (18-62) :

1. Treated at Clinic for Sexual Assault with stable symptoms.
2. Fulfill screening criteria of DSM-V for PTSD. -

Exclusion Criteria:

1. Pregnancy.
2. Fulfill screening criteria of DSM-V for psychosis.
3. Substance dependence or abuse other than nicotine.
4. Diagnosis of a neurodegenerative disease.
5. Acute illness that could be worsen by the treatment. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EFP-NF (participants without steady menstrual cycle).; EFP-NF training, twice a week for a total of 10 sessions .	Device: EFP-NF training; Experimental groups (among participants with and without steady menstrual cycle) will receive a total of 10 training sessions during 10 weeks. In addition to EFP-NF training, participants in the experimental groups will continue to be treated as usual at Clinic for Sexual Assault.
No Intervention: TAU; Participant will receive no EFP-NF training, and continue their treatment as usual (TAU).
Experimental: EFP-NF during HIGH estrogen phase; EFP-NF training, twice a week, during high-estrogen phases only (days 7-21 of a 28-day cycle), for a total of 10 sessions.	Device: EFP-NF training; Experimental groups (among participants with and without steady menstrual cycle) will receive a total of 10 training sessions during 10 weeks. In addition to EFP-NF training, participants in the experimental groups will continue to be treated as usual at Clinic for Sexual Assault.
Experimental: EFP-NF during LOW estrogen phase; EFP-NF training, twice a week, during low-estrogen phases only (days 21-28 of a cycle and days 1-7 of the following cycle,based on a 28-day cycle), for a total of 10 sessions.	Device: EFP-NF training; Experimental groups (among participants with and without steady menstrual cycle) will receive a total of 10 training sessions during 10 weeks. In addition to EFP-NF training, participants in the experimental groups will continue to be treated as usual at Clinic for Sexual Assault.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical measures- PSTD symptoms	Change in PTSD symptoms measured by change in Clinician-Administered PTSD Scale (CAPS)	The clinical assessment will be administrated at pre-treatment (baseline) and post-treatment (up to two weeks post-treatment). Additional post-treatment measurements will be administrated at three follow-ups points; 1 month, 3 months and 6 months post

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in limbic system connectivity as measured by fMRI	Using fMRI, specific changes in limbic system connectivity will be assessed. Changes in areas in the PFC and limbic regions, all will be measured at post- vs. pre-treatment times	fMRI will be administrated at pre-treatment (baseline) and post-treatment (up to two weeks post-treatment).
Sleep quality- REM latency and sleep latency	WatchPAT (wearable technology) will track REM latency and sleep latency . These will be compared and corrected using MANOVA as an outcome analysis. To assess sleep globally, we will aggregated: increased sleep latency , reduced sleep efficiency (the ratio of the total time spent asleep compared to the total amount of time spent in bed) and lack of proper deep sleep (quantified using "deep sleep percent" and "REM sleep percent", i.e. the ratio of the total time spent in deep/REM sleep out of the total sleep time) into one reported value. For full explanation and calculation of index see Goldway, et al. (2019).	Two nights; first, at pre-treatment (baseline) and second, post-treatment (up to two weeks post-treatment). A post-treatment evaluation will take place within two weeks post treatment (3-3.5 month since the beginning of the study).
Emotional regulation choice task	Behavioral - emotional regulation choice task. A computer-based task designed by Sheppes et al. (2011) was used to assess participants'choice between distraction and reappraisal when facing negatively valenced stimuli.	Emotional regulation tasks will be administrated at pre-treatment (baseline) and post-treatment (up to two weeks post-treatment).
Self-report questionnaires- PCL (PTSD checklist )	A self-report measure (20 items) of PTSD symptoms reflecting the diagnostic criteria of DSM 4+5. The self-report rating scale is 0-4 for each symptom, Rating scale descriptors are: "Not at all," "A little bit," Moderately," "Quite a bit," and "Extremely." A total symptom severity score (range - 0-80) is obtained by summing the scores for each of the items, higher values represent more severe PTSD. Symptom cluster severity scores is obtained by summing the scores for the items within a given cluster, i.e. for DSM 5: cluster B (items 1-5), cluster C (items 6-7), cluster D (items 8-14), and cluster E (items 15-20).	The Self-report questionnaires will be administrated: pre-treatment (baseline), post-treatment (up to two weeks post-treatment).and at three follow-ups points; 1 month, 3 months and 6 months post treatment
Self-report questionnaires- Beck Depression Inventory (BDI-II)	A 21 item self-administered inventory of depression symptoms and their respective intensity. BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63. higher values represent more severe depression.	The Self-report questionnaires will be administrated: pre-treatment (baseline), post-treatment (up to two weeks post-treatment).and at three follow-ups points; 1 month, 3 months and 6 months post treatment
Self-report questionnaires- State-trait Anxiety Inventory (STAI)	A 20 item self-administered inventory of state and trait anxiety. All items are rated on a 4-point scale (e.g., from "Almost Never" to "Almost Always"). SUM of scores is obtained, higher scores indicate greater anxiety.	The Self-report questionnaires will be administrated: pre-treatment (baseline), post-treatment (up to two weeks post-treatment).and at three follow-ups points; 1 month, 3 months and 6 months post treatment
Self-report questionnaires- Toronto Alexithymia Scale (TAS)	20 items self-administered composing the alexithymia scale. The TAS-20 has 3 sub-scales: Difficulty Describing Feelings subscale is used to measure difficulty describing emotions. Difficulty Identifying Feeling subscale is used to measure difficulty identifying emotions. Externally-Oriented Thinking subscale is used to measure the tendency of individuals to focus their attention externally. Items are rated using a 5-point Likert scale whereby 1 = strongly disagree and 5 = strongly agree. The total alexithymia score is the sum of responses to all 20 items, while the score for each subscale factor is the sum of the responses to that subscale. Higher scores represent higher alexithymia rate.	The Self-report questionnaires will be administrated: pre-treatment (baseline), post-treatment (up to two weeks post-treatment).and at three follow-ups points; 1 month, 3 months and 6 months post treatment
Self-report questionnaires- Dissociative Experience Scale (DES)	28-item self-administered measure of frequency of dissociative experiences. higher DES scores indicate higher dissociative rates.	The Self-report questionnaires will be administrated: pre-treatment (baseline), post-treatment (up to two weeks post-treatment).and at three follow-ups points; 1 month, 3 months and 6 months post treatment
Self-report questionnaires- Locus of Control (LOC)	24 items self-administered questionnaire intended to measure internal versus external locus of control	The Self-report questionnaires will be administrated: pre-treatment (baseline), post-treatment (up to two weeks post-treatment).and at three follow-ups points; 1 month, 3 months and 6 months post treatment
Emotional regulation stroop task	emotional Stroop- emotional regulation task, participants viewed fearful or happy facial expressions with superimposed congruent or incongruent words (happy\fear) and were asked to identify the emotional expression while ignoring the words.	Emotional regulation tasks will be administrated at pre-treatment (baseline) and post-treatment (up to two weeks post-treatment).

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center
• Investigators: Principal Investigator: Miki Bloch, M.D., TASMC Israel

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2019
• Primary Completion (Anticipated): February 20, 2022
• Study Completion (Anticipated): February 20, 2022

Study Registration Dates

• First Submitted: January 10, 2018
• First Submitted That Met QC Criteria: January 24, 2018
• First Posted (Actual): January 31, 2018

Study Record Updates

• Last Update Posted (Actual): February 5, 2019
• Last Update Submitted That Met QC Criteria: February 3, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: PTSD, neurofeedback (NF)
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: 0696-17-TLV; TAMC-17-MB-0696-CTIL (Other Identifier: TAMC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes