Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03796936 |
| Other study ID # |
WRNMMC-2018-0201 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
January 11, 2019 |
| Est. completion date |
December 2020 |
Study information
| Verified date |
January 2019 |
| Source |
Walter Reed National Military Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Background and Purpose: Posttraumatic stress disorder (PTSD) and mild traumatic brain injury
(mTBI) are persistent and frequently comorbid complications of recent combat. There is no
proven treatment for mTBI, and standard treatments for PTSD frequently achieve only
transient, modest impact. Motion-assisted, Multi-modular Memory Desensitization and
Reconsolidation (3MDR) is a novel treatment for PTSD combining aspects of virtual reality
exposure therapy (VRET) and Eye Movement Desensitization and Reprocessing (EMDR), within the
Computer Assisted Rehabilitation Environment (CAREN). The added benefit of the eye movement
(EM) component of EMDR is controversial; the purpose of this pilot study is therefore to: 1)
obtain an initial estimate of the efficacy of 3MDR in service members with comorbid PTSD and
mTBI, and 2) determine the impact of EM on treatment response. The investigators hypothesize
that 3MDR will significantly improve symptom severity, both with and without EM.
Population: Participants will be active or retired service members with a history of mTBI who
meet criteria for probable PTSD on the PCL5. It is anticipated that participants will be
recruited through the Center for Neuroscience and Regenerative Medicine (CNRM) Recruitment
Core and the National Intrepid Center of Excellence (NICoE).
Design type and procedures: This is a pilot, controlled clinical trial in which all 20
participants with comorbid PTSD and mTBI receive 10 sessions (3 preparatory, 6 3MDR
treatment, and 1 conclusion), but will be randomized to either include EM (EM+) or not (EM-).
In the preparatory sessions, the therapist will help each participant select 2 songs and 14
pictures to be used in their treatment sessions. The therapist will help the participant rate
the pictures from least to most impactful. Each 3MDR treatment session will start by playing
the first song, to bring them back to the time of their trauma. This will be done while the
participant walks on the CAREN's embedded treadmill through the 3MDR virtual environment (VE)
projected onto the system's curved screen. This is followed by a display of one of their
pictures, a manifestation of their trauma, which they directly face and walk down a hallway
toward, until the picture looms before them. The therapist, standing next to the participant
along the treadmill's edge, will query the participant about what the picture means to them,
how it makes them feel, etc., while the CAREN operator superimposes key words (said by the
participant) over the picture, which the therapist later asks the participant to read aloud.
Then, for ~60 seconds, the EM+ group will see a red ball "bounce" across the screen in front
of the picture, and a number appears on the ball as it touches the screen's edge. The
participant will be asked to recite each number aloud. This element is absent for EM-
participants. All participants repeats these procedures for 5-7 pictures in each 3MDR
treatment session; the pictures used will be agreed upon by therapist and participant,
targeting more impactful pictures, whether repeats or new, in later sessions. The pictures
are followed by playing the second song, chosen to bring the participant back to present day.
The participant will walk at a comfortable pace throughout the session, with each session
lasting typically ~60 minutes. The primary outcome measure will be change in PCL-5 score from
pre- to post-intervention, with additional measures at 3 and 6 months.
Description:
This is a pilot prospective, randomized, interventional controlled clinical trial. Our study
at the NICoE site will specifically target active or retired SMs who are OIF/OEF/OND veterans
of any age and either gender who meet criteria for PTSD and have a lifetime history of mTBI.
Comorbid PTSD and mTBI is highly prevalent in SMs and veterans of the recent wars in
Afghanistan and Iraq, and having both diagnoses is associated with significantly greater
symptom severity than either PTSD or mTBI alone (Brenner et al., 2010). TBI, the great
majority of which is mTBI, is one of the most challenging, significant, and costly problems
facing the DoD, and inhibiting readiness, whether in times of war or peace. Currently, no
therapy has yet been proven efficacious in reducing persistent symptoms after TBI. Many
patients with PTSD, particularly when it is combat-related, still suffer from substantial
residual symptoms even after undergoing evidence-based psychotherapy (Watts et al., 2013;
Bradley et al., 2001; Bison et al., 2007) and many even maintain their PTSD diagnosis
(Steenkamp et al., 2015). The novel elements of 3MDR may prove to be particularly beneficial
for those with both PTSD and a history of mTBI. If our approach is proven effective, there
will be a sizeable population for whom this treatment could be provided, translating into
both individual and DoD-wide benefit. Both TBI and PTSD have become signature wounds of the
wars in Iraq and Afghanistan and pose significant health concerns for many military
personnel. Currently, no intervention has yet been proven efficacious in reducing long-term
symptoms of TBI. Furthermore, individuals with PTSD often have persistent symptoms even after
completing validated treatments.
The proposed research has the potential to have a significant positive impact on the care of
individuals with both PTSD and mTBI. As previously stated, 3MDR combines emotional exposure,
dual-task processing, attenuation of working memory resources, and physical activity.
Physical activity may be particularly beneficial in enhancing blood flow to the brain and
facilitating production of beneficial factors such as brain-derived neurotrophic factor
(BDNF). In addition, participants have the opportunity to demonstrate to themselves that they
can actively overcome their avoidance by approaching and walking toward, or deliberately
confronting, representations of their own traumatic memories. This approach may be
particularly useful or of interest to veterans and SMs, who are accustomed to being
physically active, may be less inclined to turn to pharmacotherapy than others with PTSD, and
also have had high dropout rates and greater resistance to established, more traditional
therapies. This relatively short treatment approach could have tremendous implications for
improvement in symptoms as well as quality of life in individuals with PTSD and mTBI. Prior
to any other study procedures, written informed consent will be obtained from each
participant by the principal investigator (PI) or another study staff member trained by the
PI to obtain informed consent. The PI will then complete a medical history and a series of
questionnaires, to include a review of inclusion and exclusion criteria, to ensure that each
participant is eligible to be enrolled in the study. A random number table will be used to
randomly assign participants to either the eye movement (EM+) or no eye movement (EM-) group.
Table 1
Weeks Months 0
1 2 3 4 5 6 7 8 9 10 3 6 Consent X
3MDR Preparatory Sessions
X X X
3MDR CAREN Sessions
X X X X X X
Wrap-up Session
X
Post-Therapy Follow-Up
X X
Intervention All participants will complete 10 treatment sessions (three preparatory
sessions, six 3MDR sessions and one concluding session; see Table 1), led by a therapist who
has been completed training in the conduct of this form of therapy, with the only difference
between the intervention groups being the presence (EM+) or absence (EM-) of the eye movement
component. Dr. Eric Vermetten, head of research at the Military Mental Health unit of the
Netherlands Ministry of Defense, and one of the developers of the 3MDR system, will conduct
the training of all study therapists, will ensure that they are fully prepared to carry out
the treatment protocol using the study manual he wrote, and he will provide regular
supervision for the study therapists throughout the conduct of the study.
Preparatory Session 1: Research personnel will explain the upcoming 3MDR therapy sessions.
Participants will be asked to identify 14 photographs, as well as two songs. The photographs
may be digital, hard copy, or downloaded from the internet, and should be related to or
reminiscent of the participant's traumatic experience. Each of the two songs are selected for
specific purposes and will be played in their entirety during each of the 3MDR sessions. The
first song is intended to bring them back to the time in which the trauma occurred; for
example, for a service member with combat-related PTSD, this might be a song that they
listened to a lot during their deployment. This will be played at the start of the 3MDR
session while the participant walks at a comfortable pace through a virtual environment,
before any of their pictures are displayed. The second song, on the other hand, is
specifically chosen in order to bring them back to the present time, to remind them they are
safe and are in the present moment.
Preparatory Session 2: The participant will share their photographs and music selections with
the therapist. If the participant has difficulty identifying a sufficient number of
appropriate photographs, the therapist will work with the participant during this session to
identify why they may not have been able to come up with a sufficient number, and to help
them find suitable options. This could include conducting online searches for publicly
available pictures, including such options as Google Maps images of the area in which their
trauma occurred. Sometimes, difficulty in the selection of pictures is a manifestation of the
avoidance of any reminders of the traumatic, which is a cardinal feature of PTSD. The
therapist may at this time explore the avoidance, if it is perceived to be a significant
factor, and help the participant to work through and overcome it to a sufficient degree to
identify suitable pictures to use in the treatment sessions. While the selection of songs
does not usually pose as significant a challenge, the therapist will also review the
participant's song selections, discuss why they were chosen, and try to ensure that the songs
selected are suitable to take the participant back to the trauma, and then bring them back to
the present and help them differentiate past from present, respectively. The therapist will
then guide the participant to arrange their photographs according to their subjective units
of distress (SUDS; Wolp,1969). The SUDS is a verbal self-report rating of subjective distress
on a scale from 0-10, with 0 indicating no distress, and 10 representing maximum distress.
The SUDS scale will be explained verbally to the participant and is not given via pencil and
paper format. This will be used to rank the pictures for use during 3MDR treatment.
Preparatory Session 3: Participants will be introduced to, and familiarized with, the CAREN
system (e.g., standing, shifting weight, and walking) located at the National Intrepid Center
of Excellence (NICoE). Participants will be fitted by the engineer with a safety harness that
will be worn for the entirety of each session that a participant is on the CAREN platform. In
this session, a series of introductory applications will be used to familiarize the
participant with the CAREN, which will take less than five minutes to perform. A short
practice 3MDR session with a non-affecting photograph (e.g., a flower) will be conducted.
3MDR Sessions 1-6: A 3MDR trained therapist, as well as a CAREN engineer, will be present at
every 3MDR therapy session.
Since sessions only include level treadmill walking, the platform will be disengaged with the
bridge extended, as opposed to being separated from the main floor and set up to enable
left-right and forward-backward shifts from the horizontal. This will minimize equipment
noise and facilitate the communication between the therapist and participant. For participant
monitoring and objective data collection, heart rate and kinematic data will be collected. A
chest strap heart rate monitor will be worn by the participant throughout the session (Polar
Electro Inc., Woodbury, NY; Zephyr Performance Systems, Annapolis, MD). Reflective motion
capture markers will be placed on the participant's head, torso, and legs to measure
biomechanics collected via motion capture cameras (Motion Analysis Inc., Santa Rosa, CA) that
surround the CAREN.
Participants will then be fitted with an adjustable safety harness that fits comfortably over
the shoulders. There is a risk of skin chafing if there is a lot of movement and the harness
is not fitted properly. Each participant will be asked if they are comfortable throughout the
study to mitigate this risk. The safety harness will be slipped into the safety support on
the CAREN, which allows the participant to walk freely on the treadmill, but it does not
allow them to walk off the platform. There is also a safety bar in front of the participant.
The therapist will stand next to the participant during the session, on the edge of the
platform but not on the treadmill. Up to seven pictures will be selected based on the
participant's SUDS scores and/or themes agreed upon for each session. Pictures may be
repeated during a session, reducing the number of pictures used for some sessions; this will
be at the discretion of the treating therapist.
Each session has three phases: warm-up, intervention, and cool-down. The participant's
preferred walking speed will be used to start the warm-up phase (2-5 min) and can be adjusted
as needed. During this phase, the participant will virtually walk along an outdoor pathway
toward a door while their chosen opening song plays to bring them back to a time of their
trigger, as verbal guidance from their therapist prepares them for the intervention phase.
The CAREN system will be operated by a Biomedical Engineer, Sarah Kruger, who has been
operating CAREN systems since 2007, and is certified by Motekforce Link. Motekforce Link is
the manufacturer of the CAREN system. Motekforce Link provides CAREN operators with training
and also verifies competencies required for system operation.
During utilization, the system is operated by a certified CAREN Operator and per protocol, at
no time will the system be operated with less than two staff members in the room.
System checks are run daily by the CAREN Operator. All equipment is calibrated and
maintained. Personnel from Motekforce Link visit annually to verify that everything is
working properly and make any changes that are necessary.
In the intervention phase (50-55 min), the participant passes through an initial hallway
leading to an open door that in turn leads them down a second hallway to approach their first
picture, while being guided by the therapist with regard to what to do at each stage. The
picture appears in the distance, but gradually becomes larger as they get closer to it, until
it fills their field of vision. As soon as the participant is able to see the picture
clearly, the therapist will request that they provide a detailed description of what the
picture represents to them, and will then go on to ask the participant about their related
memories and feelings. The therapist will verbally repeat key feelings and phrases that seem
to carry particular meaning and resonance for the participant, so the CAREN engineer can type
these words into the computer to have them appear superimposed over the picture (stage 1).
For those in the EM+ intervention group, the EM component will start after the participant
has confirmed there are no more new feelings or words to be identified with the picture, and
the therapist has asked the participant to read each of these words aloud, after which the
engineer will remove the words from the screen but retain the picture. At this point a red
ball will start at the left edge of the screen, and will move across the screen fairly
rapidly from left to right, and upon reaching the right edge of the screen, a 2-digit number
will appear superimposed on the red ball in white font (stage 2). The ball will then reverse
course, passing from right to left, and the number will change as the ball meets the opposite
edge of the screen. The ball will continue to move back and forth and the number will change
every time the ball meets either edge of the screen. The participant will be asked to track
the ball and call out the numbers displayed on the ball. After approximately 60 seconds, the
distractor stimulus (ball image) is removed and a SUDS score is reported by the participant
and recorded by the CAREN operator (stage 3). The participant will then walk out of the
virtual hallway and onto an outdoor pathway that will lead them to another set of hallways,
leading in turn to another picture, and the stages are repeated. There will be no exposure to
the distractor stimulus (red ball) for those in the EM- intervention group.
After the last picture, the final phase of treatment (cool-down) begins (2-5 min). The
session concludes with a piece of music, chosen by the participant to bring them back to the
present time, typically a current favorite song of theirs. This music will be used to assist
the participant in returning back to the present moment, while the therapist simultaneously
provides them with positive feedback regarding their performance during the session, with a
goal of achieving a significantly reduced SUDS score, which is reassessed at the end of the
song.
Following the session, the CAREN operator will remove the safety harness from the
participant. Participants will also be able to stop the session at any time if they feel ill
or any motion sickness. A therapist-led discussion (approximately 15 minutes) with the
participant will then occur in a private room; open questions will be used to elicit how the
session was for the participant, and to discuss the purpose of re-experiencing to the
participant in this setting. Notes made by the therapist will be stored, identified by study
code and session number only, stored in password-protected files on a CAC-requiring computer.
The study therapist will ensure the participant has completely returned to the present
moment, has a reduced SUDS, and has ideally been able to attach a positive meaning to the
3MDR session. Participants will be asked to write their experiences and reflections down
following each session in a diary format. All sessions will be recorded and a report
summarizing the behavioral response to the intervention will be produced.
Concluding Session: Participants will provide their perception of how beneficial the
treatment was, and if the current state of their symptoms will be discussed, with a focus on
to what degree they have or have not improved compared to prior to their participation in the
study.
Participants will return to the laboratory to complete follow-up assessments at 3 and 6
months. If participants are unable to return to the laboratory (i.e., no longer in the area),
they will be contacted via phone, and the study questionnaires will be completed
telephonically.
