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Trial registered on ANZCTR


Registration number
ACTRN12624001404516p
Ethics application status
Submitted, not yet approved
Date submitted
29/10/2024
Date registered
27/11/2024
Date last updated
27/11/2024
Date data sharing statement initially provided
27/11/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Rapid eye movement sleep & extinction trial in post-traumatic stress disorder
Scientific title
A randomised, double-blind, placebo-controlled trial on the effect of lemborexant on sleep and emotional memories in adults aged 18 to 50 with PTSD.
Secondary ID [1] 313265 0
None
Universal Trial Number (UTN)
Trial acronym
Trauma RESET
Linked study record

Health condition
Health condition(s) or problem(s) studied:
PTSD 335591 0
Trauma 335592 0
Condition category
Condition code
Mental Health 332161 332161 0 0
Other mental health disorders
Neurological 332356 332356 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This Randomized Controlled Trial (RCT) investigates whether the dual orexin receptor antagonist lemborexant increases rapid eye movement (REM) sleep and improves fear extinction recall compared to a placebo control.

Participant with previous trauma exposure and PTSD will be recruited and randomly assigned to the double-blinded drug condition. The intervention group receives one dose of 10mg lemborexant orally about 1h before bedtime.
On the test day, participants will complete a standardized and well-validated fear conditioning and extinction task which examines their capacity to acquire conditioned fear (via recording skin conductance response [SCR] reflecting physiological arousal to stimuli paired with a mild electric shock) and extinguishing fear. Prior to the task, the level of shock will be individually set at a level that is uncomfortable, but not painful. For the fear acquisition phase, they will look at visual images of a scene containing a desktop lamp which lights up with a color. One color will be associated with a mild electrical shock (the CS+), the other colored circle is never associated with shock (the CS-). This will be followed immediately by the fear extinction phase in which they will look at both colored lights which will never be followed by shock. This paradigm is adapted from Milad, Orr, Pitman, & Rauch (2005) and the approximate duration of the task is 20 minutes. SCR will be recorded to reflect sympathetic arousal. SCR amplitude typically increases to the CS+ compared to the CS- in the acquisition phase, and then gradually reduces over the extinction phase. The slope of decline of SCR over the fear extinction phase reflects how well an individual can inhibit/regulate their fear and reflects their capacity for fear extinction learning. Next, participants view emotive and neutral images selected from the International Affective Picture System (IAPS, task duration approximately 10 minutes). Then, participants will take the drug (oral tablet) under direct supervision by research staff and sleep at the lab while polysomnography (PSG) records sleep including REM sleep during the test night. This is followed by a recovery night at home to allow full drug washout (an ambulatory PSG records REM sleep during the recovery night). The participants return to the lab the next morning for the follow up. First they are asked to remember, recognized and rate the IAPS images they have seen two days before. Then, they complete the extinction phase again while SCR is recorded to measure recall of fear extinction. The extent that their fear returns reflects how well they remember the fear extinction from the first test day. The following week, participants record any intrusive memories that they have of the IAPS images.
Intervention code [1] 329845 0
Treatment: Drugs
Intervention code [2] 329981 0
Treatment: Other
Comparator / control treatment
The participants in the placebo control group will receive the tablet in the form of a capsule (ingredient: hypromellose) filled with sugar 1h before bedtime.
Control group
Placebo

Outcomes
Primary outcome [1] 339748 0
Fear extinction recall
Timepoint [1] 339748 0
Follow up (about 48h after drug intake).
Primary outcome [2] 339749 0
Rapid eye movement sleep
Timepoint [2] 339749 0
Test night (night after drug intake)
Primary outcome [3] 339750 0
Emotional memory
Timepoint [3] 339750 0
Follow up (about 48h after drug intake).
Secondary outcome [1] 441105 0
Number and description of intrusive memories (assessed from the open-ended question of the intrusive memory diary).
Timepoint [1] 441105 0
Daily for 7 days post follow-up (about 48h after drug intake)
Secondary outcome [2] 441106 0
Rapid eye movement sleep
Timepoint [2] 441106 0
Sleep during second night after drug intake (recovery night)
Secondary outcome [3] 441899 0
Emotional memory
This is an additional primary outcome
Timepoint [3] 441899 0
Follow up (about 48h after drug intake).
Secondary outcome [4] 441901 0
Emotional memory
This is an additional primary outcome
Timepoint [4] 441901 0
Follow up (about 48h after drug intake).

Eligibility
Key inclusion criteria
Previous trauma-exposure and PTSD Checklist for DSM-5 (PCL-5) score >30
Proficient in English
Minimum age
18 Years
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Severe mental disorders: personality disorder and bipolar disorder, actively suicidal, experiencing psychosis, schizophrenia, or major addiction
- Physical disorder including severe hepatic or renal impairment, neurological disorders including narcolepsy, epilepsy or seizures, and/or cardiac disorders including hypo- or hypertensions (blood pressure outside 90/60mmHg - 140/90mmHg)
- Sleep disorder (unmanaged), or sleep disturbance including jetlag or recent shift work
- Currently taking medication that interacts with the study drug. Contraceptive pills are ok.
- Regular smokers (social smokers are ok)
- BMI outside 18.5 – 30kg m2
- Participants who routinely go to bed after 1am
- Biologically female participants: pregnant, breastfeeding and/or trying to get pregnant

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The drug will be administered in a white, opaque, numbered plastic bottle.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation stratified by sex will be done by a non-involved third party that has no contact with participants and will prepare the randomisation list for the researcher.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Data will be analysed using a variety of methodologies depending on the dependent variable.

T-test and effect size analyses will test difference in REM sleep amount and fear extinction amongst drug conditions.

To assess group differences on fear conditioning and extinction learning, 2 (Drug Condition: lemborexant, placebo) x 2 (Condition: CS+/CS-) x 5 (trial) mixed model ANOVAs will be conducted. To assess group differences on extinction recall, the average SCR to the first two trials at recall will be compared between drugs. To assess the drug effect on sleep and extinction recall, multple linear regressions will be conducted.

To examine group differences in emotion memory data (memory recall, intrusive memories), a 2 (Drug: lemborexant/placebo) x 3 (Valence: Negative, Neutral, Positive) mixed model ANOVA or linear regressions when including REM sleep will be used.

The significance level is set to a = 0.05, indicating a p-value < a to be statistically significant.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/12/2024
Actual
Date of last participant enrolment
Anticipated
7/12/2026
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 317716 0
University
Name [1] 317716 0
the University of Melbourne
Country [1] 317716 0
Australia
Primary sponsor type
University
Name
the University of Melbourne
Address
Country
Australia
Secondary sponsor category [1] 320034 0
None
Name [1] 320034 0
Address [1] 320034 0
Country [1] 320034 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 316408 0
University of Melbourne Central Human Research Ethics Committee
Ethics committee address [1] 316408 0
Ethics committee country [1] 316408 0
Australia
Date submitted for ethics approval [1] 316408 0
29/10/2024
Approval date [1] 316408 0
Ethics approval number [1] 316408 0
31292

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 137794 0
Prof Kim Felmingham
Address 137794 0
The University of Melbourne's School of Psychological Sciences, Level 12, 17 Spencer Street, Parkville VIC 3010
Country 137794 0
Australia
Phone 137794 0
+61 03 8344 1523
Fax 137794 0
Email 137794 0
k.felmingham@unimelb.edu.au
Contact person for public queries
Name 137795 0
Maya Schenker
Address 137795 0
The University of Melbourne's School of Psychological Sciences, Level 9, 17 Spencer Street, Parkville VIC 3010
Country 137795 0
Australia
Phone 137795 0
+61390354863
Fax 137795 0
Email 137795 0
m.schenker@unimelb.edu.au
Contact person for scientific queries
Name 137796 0
Maya Schenker
Address 137796 0
The University of Melbourne's School of Psychological Sciences, Level 9, 17 Spencer Street, Parkville VIC 3010
Country 137796 0
Australia
Phone 137796 0
+61390354863
Fax 137796 0
Email 137796 0
m.schenker@unimelb.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.