Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000535572
Ethics application status
Approved
Date submitted
15/05/2015
Date registered
27/05/2015
Date last updated
20/01/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
The effects of prazosin on Rapid Eye Movement (REM) sleep and emotional memory in healthy young adults
Scientific title
Placebo-controlled analysis of the effects of prazosin on REM sleep and emotional memory in healthy adults aged 18-39.
Secondary ID [1] 286519 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post Traumatic Stress Disorder (PTSD) 294740 0
Condition category
Condition code
Mental Health 295025 295025 0 0
Studies of normal psychology, cognitive function and behaviour

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be put on a upward titrating dose of prazosin for 16 consecutive days, followed by a downward titrating dose for 6 consecutive days. The dosing schedule is: 2 days of 0mg (placebo), 2 days of 1mg, 3 days of 2mg, 3 days of 4mg and 6 days of 8mg. Then, 2 days of 4mg, 2 days of 2 mg, and 2 days of 1mg . Medication is taken as 2 capsules at bedtime. Medication containers will be return to the study team as a check for adherence.
Intervention code [1] 291613 0
Treatment: Drugs
Comparator / control treatment
Placebo: Avicel powder in a capsule that looks identical to the active medication
Control group
Placebo

Outcomes
Primary outcome [1] 294784 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] 294784 0
Primary outcomes will be measured on nights 2, 9, and 16 of the prazosin protocol; doses 0mg (placebo), 4mg and 8mg respectively.
Primary outcome [2] 295135 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] 295135 0
Primary outcomes will be measured on nights 2, 9, and 16 of the prazosin protocol; doses 0mg (placebo), 4mg and 8mg respectively.
Primary outcome [3] 295136 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] 295136 0
Primary outcomes will be measured on nights 2, 9, and 16 of the prazosin protocol; doses 0mg (placebo), 4mg and 8mg respectively.
Secondary outcome [1] 314041 0
Emotional memory: Positive, negative and neutral picture recall.
Timepoint [1] 314041 0
The International Affective Picture System (IAPS) is a database of pictures used to elicit a range of emotions. Three parallel sets of IAPS pictures will be used to test emotional memory. The sets will be learned on nights 2, 9 and 16 (at 0mg, 4mg and 8mg doses of prazosin), then tested on the morning of the 3rd, 10th and 17th days.

All participants will partake in three conditions: low, medium and high REM, corresponding to prazosin doses (0mg, 4mg and 8mg, respectively). The outcome variable for the memory test will be d’, a discriminability index measuring the extent to which a participant can discriminate between targets and foils. It provides an overall measure of recognition memory.
Secondary outcome [2] 314042 0
Melatonin secretion magnitude
Timepoint [2] 314042 0
Melatonin secretion magnitude will be measured as the last urine sample before bed and the first sample upon waking. This magnitude will be averaged over nights 1-2, 8-9 and 15-16) for 3 secretion magnitude measures corresponding to each prazosin dose taken (0mg, 4mg and 8mg).

Eligibility
Key inclusion criteria
Aged 18-39, healthy, with a consistent sleep schedule
Minimum age
18 Years
Maximum age
39 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Regular sleep/wake schedule not corresponding to the night/day cycle (e.g. shift workers), any sleep disorders.
- Personal history of Axis 1 psycho-pathology, or family history of mood and psychotic disorders.
- History of head injuries, loss of consciousness above 15 minutes, migraines requiring treatment, or seizures.
- Current use of psychotropic medications or a positive urinary toxicology for illegal substances.
- Current use of medication that affects the central-nervous system (e.g. Beta-blockers or anti-depressants)
- Consumption of > 14 standard drinks of alcohol per week
- Smokers or people undergoing nicotine replacement therapies (unless ceased over 12 months ago)
- Consumption of > 300mg of caffeine per day
- Use of erectile dysfunction medication
- Use of other hypertension drugs
- Severe peripheral edema
- Supine hypotension and/or clinically meaningful hypotension
- Plans to have any medical or dental procedures requiring general anesthetic during the study
- Are pregnant or trying to get pregnant during the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will respond to advertisements then undergo phone and in-person screening with researchers and a physician to examine whether they fit the inclusion/exclusion criteria. Participants will all undergo the same treatment procedure.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Pharmacodynamics
Statistical methods / analysis
A Polysomnography (PSG) will be used to record overnight brain-wave activity in participants. This will provide a measure of REM minutes, REM onset latency and REM efficiency. Changes in these measures with increasing doses of prazosin (placebo, 4mg, 8mg) will be analysed using three separate 3-level repeated-measures ANOVAs.

The outcome variable for the memory test will be d’, a discriminability index measuring the extent to which a participant can discriminate between targets and foils. It provides an overall measure of recognition memory. A 3 (REM conditions) x 3 (valence) repeated-measures ANOVA will be conducted. If the interaction is significant, the main effect of REM condition within each valence will be examined.


Melatonin secretion magnitudes will be calculated as the average between the last sample before bed and first sample upon awakening on each lab visit. These values will also be compared with a 3-level, one-way repeated-measures ANOVA to look for differences between the 3 dosages of Prazosin.

Posthoc tests will be used to determine where any significant differences lie.

As this is the first study to examine the effects of prazosin on REM sleep in healthy controls, we designed it as a pilot study to estimate an effect size for a larger study. The sample size was chosen based those used in the smaller published clinical studies demonstrating an effect of prazosin on nightmares.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
18/05/2015
Actual
20/05/2015
Date of last participant enrolment
Anticipated
31/05/2016
Actual
19/08/2015
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 291084 0
University
Name [1] 291084 0
School of Psychological Sciences
Monash University
Country [1] 291084 0
Australia
Primary sponsor type
University
Name
School of Psychological Sciences
Address
Monash University,
18 Innovation Walk, Clayton Campus,
Wellington Road,
Monash University, VIC, 3800
Australia
Country
Australia
Secondary sponsor category [1] 289761 0
None
Name [1] 289761 0
Address [1] 289761 0
Country [1] 289761 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292666 0
Monash University Human Ethics Committee
Ethics committee address [1] 292666 0
Building 3e Room 111
Research Office
Monash University VIC 3800
Ethics committee country [1] 292666 0
Australia
Date submitted for ethics approval [1] 292666 0
Approval date [1] 292666 0
12/05/2015
Ethics approval number [1] 292666 0
CF15/772 - 2015000345

Summary
Brief summary
The purpose of this study is to examine the effects of the medication prazosin on: 1) the quantity and quality of Rapid Eye Movement (REM) sleep; and 2) emotional memory. This is so we can learn more about the basic effects of the medication in healthy adults as a step towards better understanding how the medication might help those with Posttraumatic Stress Disorder.

The hypotheses are:
1. Increasing doses of prazosin will lead to greater quantity of REM sleep and fewer disruptions of REM sleep (e.g., fewer awakenings during REM sleep)
2. Increasing quality of REM sleep, resulting from increasing doses of prazosin, will lead to improved overnight memory for emotional pictures.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes

Contacts
Principal investigator
Name 56474 0
Prof Sean P.A. Drummond
Address 56474 0
Monash University
School of Psychological Scienes
18 Innovation Walk, Clayton Campus,
Wellington Road,
Monash University, VIC, 3800
Australia
Country 56474 0
Australia
Phone 56474 0
+61 3 9905 3956
Fax 56474 0
Email 56474 0
[email protected]
Contact person for public queries
Name 56475 0
Prof Sean P.A. Drummond
Address 56475 0
Monash University
School of Psychological Scienes
18 Innovation Walk, Clayton Campus,
Wellington Road,
Monash University, VIC, 3800
Australia
Country 56475 0
Australia
Phone 56475 0
+61 3 9905 3956
Fax 56475 0
Email 56475 0
[email protected]
Contact person for scientific queries
Name 56476 0
Prof Sean P.A. Drummond
Address 56476 0
Monash University
School of Psychological Scienes
18 Innovation Walk, Clayton Campus,
Wellington Road,
Monash University, VIC, 3800
Australia
Country 56476 0
Australia
Phone 56476 0
+61 3 9905 3956
Fax 56476 0
Email 56476 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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