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Trial registered on ANZCTR


Registration number
ACTRN12618001624279
Ethics application status
Approved
Date submitted
26/09/2018
Date registered
3/10/2018
Date last updated
3/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of tasimelteon, administered prior to sleep at an irregular time, on Rapid Eye Movement (REM) sleep and fear inhibition in healthy young adults
Scientific title
Placebo-controlled analysis of the effects of tasimelteon, administered prior to circadian misalignment, on REM sleep and fear inhibition in healthy adults aged 18-39 years
Secondary ID [1] 296175 0
None
Universal Trial Number (UTN)
U1111-1221-1031
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Posttraumatic Stress Disorder (PTSD) 309804 0
Condition category
Condition code
Mental Health 308598 308598 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will undergo a 4-night/4-day experimental protocol. Night 1 is an adaptation night for habituation to sleeping within a laboratory environment. Participants will undergo normal, undisturbed sleep on Night 2. Participants then undergo circadian misalignment on Night 3 (i.e., a sleep opportunity is advanced 8-hours from the typical sleep schedule for each participant). Participants will be administered tasimelteon 20mg (experimental condition) or placebo (control condition) in capsule form 30 minutes prior to the advanced bedtime (a single dose of medication or placebo is administered in this experimental protocol). Medication and placebo containers will be returned to the study team as a check for adherence. Finally, participants will undergo normal, undisturbed sleep on Night 4 (i.e., recovery sleep).
Intervention code [1] 312505 0
Treatment: Drugs
Comparator / control treatment
Placebo group: Participants are administered Avicel powder in a capsule that looks identical to the active medication prior to circadian misalignment

Well-rested/untreated group: Untreated participants maintain a typical sleep-wake schedule throughout testing.
Control group
Placebo

Outcomes
Primary outcome [1] 307561 0
- REM minutes (the total amount of minutes spent in REM sleep over the course of the night), assessed with overnight sleep study using polysomnography.
Timepoint [1] 307561 0
REM minutes is assessed on nights 2, 3 (primary time point), and 4 of the study protocol.

.
Primary outcome [2] 307562 0
- REM efficiency (the percentage of epoch's during a REM episode measured as REM - a measurement of REM fragmentation), assessed with overnight sleep study using polysomnography
Timepoint [2] 307562 0
REM efficiency is assessed on nights 2, 3 (primary time point), and 4 of the study protocol.
Primary outcome [3] 307563 0
REM onset latency (the time it takes between sleep onset and the appearance of REM sleep), assessed with overnight sleep study using polysomnography.
Timepoint [3] 307563 0
REM onset latency is assessed on nights 2, 3 (primary time point), and 4 of the study protocol.
Secondary outcome [1] 352295 0
Fear and safety learning, defined as the ability to learn visual cues predict fear or safety, respectively. Fear and safety learning are assessed using the fear-potentiated startle paradigm described in Norrholm, et al., (2006) Learning & Memory, 13, 681-685.
Timepoint [1] 352295 0
Fear and safety learning are tested on day two of the study protocol.
Secondary outcome [2] 352296 0
Fear and safety learning recall, defined as the ability to recall visual cues predict fear or safety, respectively. Fear and safety learning recall are assessed using the fear-potentiated startle paradigm described in Norrholm, et al., (2006) Learning & Memory, 13, 681-685.
Timepoint [2] 352296 0
Fear and safety learning recall are tested on day three of the study protocol.
Secondary outcome [3] 352298 0
Fear extinction, defined as the ability to learn that visual cues previously associated with 'threat' should no longer be feared. Fear extinction is assessed using the fear-potentiated startle paradigm described in Norrholm, et al., (2006) Learning & Memory, 13, 681-685.
Timepoint [3] 352298 0
Fear extinction is tested on day three of the study protocol.
Secondary outcome [4] 352299 0
Fear extinction recall, defined as the ability to recall that visual cues previously associated with 'threat' should no longer be feared. Fear extinction recall is assessed using the fear-potentiated startle paradigm described in Norrholm, et al., (2006) Learning & Memory, 13, 681-685.
Timepoint [4] 352299 0
Fear extinction recall is tested on day four of the study protocol.

Eligibility
Key inclusion criteria
Inclusion criteria are: 1) age 18–39 years-old; 2) regular sleep-wake schedule; 3) no current and unmanaged medical or psychiatric diagnoses; and d) no personal history of any Axis I diagnosis or family history of mood or psychotic disorders. Also, female participants will be studied in the early follicular phase of the menstrual cycle.
Minimum age
18 Years
Maximum age
39 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria are: 1) any sleep disorder revealed on the adaptation night (e.g., sleep apnea); and 2) not exhibiting consistent startle responding on the screening day (i.e., over 75% discernible responses to 6 108-dB 40-ms startle pulses).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 300767 0
Government body
Name [1] 300767 0
United States Department of Defence (DoD)
Address [1] 300767 0
1400 Defense Pentagon,
Washington, DC 20301-1400
Country [1] 300767 0
United States of America
Primary sponsor type
University
Name
Monash University
Address
Monash University,
Clayton Campus, Wellington Road,
Clayton, Victoria 3800
Country
Australia
Secondary sponsor category [1] 300306 0
None
Name [1] 300306 0
Address [1] 300306 0
Country [1] 300306 0
Other collaborator category [1] 280364 0
Charities/Societies/Foundations
Name [1] 280364 0
Veterans Medical Research Foundation
Address [1] 280364 0
Building 13
3350 La Jolla Village Dr #151A
San Diego, CA 92161,
Country [1] 280364 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301548 0
Monash University Human Research Ethics Committee (MUHREC)
Ethics committee address [1] 301548 0
First Floor, Room 111
Chancellery Building E
24 Sports Walk
Monash Research Office
Clayton Campus
Monash University VIC 3800
Ethics committee country [1] 301548 0
Australia
Date submitted for ethics approval [1] 301548 0
18/07/2017
Approval date [1] 301548 0
29/08/2017
Ethics approval number [1] 301548 0
9938

Summary
Brief summary
Circadian misalignment disrupts REM sleep, a stage of sleep which is important for fear memory processing. The aim of this study is to explore whether the sleep aid tasimelteon, when administered prior to circadian misalignment, will rescue REM sleep and recover fear inhibition processes. This study will provide important insight into the relationship between REM sleep and processes critical for treatment and recovery from Posttraumatic Stress Disorder (PTSD).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 87350 0
Prof Sean P.A. Drummond
Address 87350 0
Monash University
School of Psychological Sciences
18 Innovation Walk, Clayton Campus,
Wellington Road,
Monash University, VIC, 3800
Australia
Country 87350 0
Australia
Phone 87350 0
+61 3 9905 3956
Fax 87350 0
Email 87350 0
sean.drummond@monash.edu
Contact person for public queries
Name 87351 0
Prof Sean P.A. Drummond
Address 87351 0
Monash University
School of Psychological Sciences
18 Innovation Walk, Clayton Campus,
Wellington Road,
Monash University, VIC, 3800
Australia
Country 87351 0
Australia
Phone 87351 0
+61 3 9905 3956
Fax 87351 0
Email 87351 0
sean.drummond@monash.edu
Contact person for scientific queries
Name 87352 0
Prof Sean P.A. Drummond
Address 87352 0
Monash University
School of Psychological Sciences
18 Innovation Walk, Clayton Campus,
Wellington Road,
Monash University, VIC, 3800
Australia
Country 87352 0
Australia
Phone 87352 0
+61 3 9905 3956
Fax 87352 0
Email 87352 0
sean.drummond@monash.edu

No data has been provided for results reporting
Summary results
Not applicable