The two primary objectives of this study are: 1. To increase therapeutic effectiveness of an EMDR treatment session in PTSD patients by reactivating the updated traumatic memory during post-treatment sleep using TMR; and 2. To provide a neural base…
ID
Source
Brief title
Condition
- Anxiety disorders and symptoms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The following primary study parameters will be assessed pre- and post TMR:
1. Subjective (e.g. ratings of distress, vividness and emotionality) and
physiological (heart rate and salivary cortisol) indexes of fear and arousal
related to the targeted, traumatic memory as probed during a script-driven
recall and imagery procedure (symptom provocation task);
2. Overall PTSD symptom level;
3. Number of intrusions (and related level of distress) of the targeted
traumatic memory;
4. Brain activation and functional connectivity patterns as measured with fMRI
during a script-driven imagery task.
Secondary outcome
The following secundary study parameters will be obtained during 1 week (or
several days) before and during intervention to test their association with the
TMR effect:
- Divers sleepparameters such as subjective and objective sleep quality,
percentage of time spent in (non-)REM sleep, number and density of sleep
spindles and spectral power in the theta, delta and sigma range of the
respective sleep phases.
The following secundary study parameters will be obtained 1 day before
intervention and compared between PTSD patients and trauma controls:
- Brain activation patterns and functional connectivity patterns as measured
with fMRI during the script-driven imagery task.
The following secundary study parameters will be obtained during intervention
and compared between PTSD patients (in the No reactivation group) and trauma
controls:
- Divers sleepparameters as mentioned above.
Background summary
Post-traumatic stress disorder (PTSD) is a severe mental disorder associated
with significant personal and societal burden. Traumatic memories are at the
core of its pathophysiology, resulting in key-symptoms such as nightmares and
flashbacks. Currently, first-choice treatment, consisting of exposure-based
psychotherapy, such as eye movement desensitization and reprocessing (EMDR),
proves ineffective in half of PTSD-patients. Hence, there is an urgent need to
improve treatment. Sleep is crucial in the treatment of traumatic memories.
During exposure-based treatment, traumatic memories get reactivated and
subsequently re-encoded with lower fear. This treatment effect is then
solidified during memory consolidation while asleep when the 'neutralized'
memories get integrated in long-term storage, stabilizing them and further
reducing their affective charge. Recent advances in basic memory research show
that memory consolidation can be significantly enhanced by presenting reminder
cues (sounds/scents that were linked to the memory at encoding) during
subsequent sleep (targeted memory reactivation (TMR)). Here, we apply these
memory reactivation strategies during sleep for the first time in (PTSD)
patients to increase therapeutic effectiveness. Using a controlled design, we
predict that re-administering auditory cues, that are already part of a
specific PTSD treatment during post-treatment sleep, will increase therapeutic
outcome. This is measured as reduced subjective and physiological fear in
relation to the targeted memory, as well as reduced overall PTSD symptom level.
To visualize the underlying transfer of the memory trace to higher-order memory
networks, we will obtain functional MRI during scripted recall of the traumatic
event pre/post study.
Study objective
The two primary objectives of this study are: 1. To increase therapeutic
effectiveness of an EMDR treatment session in PTSD patients by reactivating the
updated traumatic memory during post-treatment sleep using TMR; and 2. To
provide a neural base for this augmented treatment effect by showing a
(enhanced) system-level reorganization of the targeted memory trace using fMRI.
In addition, three secondary objectives will be investigated: 1. To test
whether diverse sleep parameters (measured both pre-treatment and during the
experimental night) are associated to the effect of TMR; 2. To test the effect
of TMR itself on sleep macro- and microstructure; and 3. To identify abnormal
brain function in PTSD by comparing structural and functional MRI measures
(e.g. resting state fMRI and script-driven imagery) between patients and trauma
controls. The groups will additionally be compared on all obtained sleep
measures to identify sleep deficits distinctive for PTSD.
Study design
All primary and secondary objectives (except secondary objective 3) will be
studied using a randomized, controlled, between-subjects design, comparing 1.
Reactivation with the EMDR sound during sleep, 2. No reactivation (treatment as
usual) during sleep, and 3. Presentation of a new sound during sleep unrelated
to the EMDR session (to rule out general effects of sound presentation during
sleep).
Intervention
Patients will be treated with a single session of EMDR by a certified
therapist. EMDR is a first-choice treatment for PTSD, which has been shown to
be safe and effective. After successful EMDR treatment, patients will undergo
TMR during post-treatment sleep. TMR is a recently described experimental
procedure which aims at strengthening memory consolidation processes during
sleep by re-administering context cues, such as auditory or olfactory stimuli,
that are linked to the targeted memory at awake encoding.
Study burden and risks
Total participation time will be approximately 22 hours over a 2,5-week time
period, consisting of 5,5 hours of clinical interviews, questionnaires and
baseline measurements, 45 minutes EMDR therapy session, approximately 1 hour
MRI scanning (2 x 30 minutes), daily diary reports of ca. 10 minutes and a
night of sleep at the sleep laboratory. Participation time for trauma controls
is 17 hours). The risk associated with participation can be considered minimal
and the burden moderate. No adverse effects of TMR have been reported.
Participation in the EMDR session and script-driven imagery procedure can cause
distress due to the exposure element in the procedures.
de Boelenlaan 1108
Amsterdam 1081HZ
NL
de Boelenlaan 1108
Amsterdam 1081HZ
NL
Listed location countries
Age
Inclusion criteria
PTSD patients
* PTSD diagnosis according to DSM-5 criteria as assessed with the CAPS-5
* PTSD as primary diagnosis
* 18-65 years of age
* Capability to provide informed consentTrauma controls
* Having experienced a type A-trauma according to DSM-5 criteria as assessed
with the LEC-5 (as part of the CAPS-5).
* No PTSD diagnosis according to DSM-5 criteria as assessed with the CAPS-5
* 18-65 years of age
Exclusion criteria
PTSD patients
* Current bipolar disorder, psychotic disorder, alcohol or substance dependence
as assessed with the M.I.N.I. International Neuropsychiatric Interview. Note
comorbid depressive or anxiety disorders will be allowed if PTSD is the primary
diagnosis.
* Current personality disorder as assessed with the SCID-5-P (preceded by a
screener)
* Active suicidal ideation
* Major head trauma or neurological disease, current or in history
* MRI contraindications such as metal implants, claustrophobia, pregnancy
* Self-reported inability or unease to cease smoking for 24 hours prior to
testing (for salivary cortisol sampling)
* Endocrinological disorders or regular use of corticosteroids (for salivary
cortisol sampling)
* Use psychotropic medication up to 6 weeks pre-study (or in case of
benzodiazepines or other sleep medication 1 week)
* Use of recreational drugs over the entire study period (Day -7 to Day 11).
* Use of alcohol during Day -7, Day 1, Night 1, Day 2, Night 2, Day 3 and Day
11.
* Irregular sleep/wake rhythm (e.g., regular nightshifts or cross timeline
travel)
* A sleep window outside 10 pm and 10 am
Trauma controls
* Any current psychiatric disorder as assessed with the M.I.N.I. International
Neuropsychiatric Interview or known to the patient her/himself.
* Lifetime PTSD diagnosis
* Impossibility to isolate a circumscribed traumatic memory that can be used
for the audioscript and for target selection in EMDR.
* Reactivation of the traumatic memory that is used for the audioscript and for
target selection in EMDR, leads to severe dissociative complaints/signs*
* Not speaking/understanding Dutch sufficiently
* Active suicidal ideation
* Major head trauma with co-occurring loss of consciousness in the recent past
* (Neurological) disorder of the central nervous system, current or in history
* MRI contraindications such as metal implants, claustrophobia, pregnancy
* Use of psychotropic medication (other than benzodiazepines or other sleep
medication), except when on a stable dose for at least 6 weeks (after start or
alteration of dosage). Use of benzodiazepines or other sleep medication in the
period of 1 week prior to study until end of study (Day 10).
* Use of recreational drugs over the entire study period (Day -7 to Day 10).
* Use of alcohol during Day -7, Day 1, Night 1, Day 2, Night 2, Day 3 and Day
10.
* Irregular sleep/wake rhythm (e.g., regular nightshifts or cross timeline
travel)
* A sleep window outside 10 pm and 10 am
* Sleep walking or REM sleep behaviour disorder
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL62909.029.17 |
| Other | Nummer NTR volgt nog |