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Towards a Post-exposition Pharmacological Prophylaxis for Post-traumatic Stress Disorder (TRAUMA-PRO)

Primary Purpose

Intrusive Thought, Psychological Trauma, Inflammatory Response

Status
Completed
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Dexmedetomidine
Gamma-Hydroxybutyrate
Placebo
Experimental Model Trauma Film
Sponsored by
Psychiatric University Hospital, Zurich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Intrusive Thought

Eligibility Criteria

18 Years - 35 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Speaks and understands German
  • BMI 18.5 -< 25
  • Non-smoker status
  • Habitual 5 or fewer alcoholic beverages / week
  • Habitual 3 or fewer caffeinated beverages / day
  • Habitual average sleep duration 7-9 h / night
  • Normal or corrected-to-normal vision
  • Insomnia Severity Index score between 8-14

Exclusion Criteria:

  • Travel across 3 or more time zones within 3 months of study start
  • Habitual napping
  • Extreme chronotype, determined by Morningness-Eveningness Questionnaire
  • History of or presence of a trauma- or stressor-related disorder
  • History of or presence of neurological disorder, psychiatric disorder or head injury
  • History of or presence of a sleep disorder
  • History of or presence of cardiovascular disorder
  • Use of illicit drugs
  • Atypical preference for excessively violent portrayals
  • Faints at the site of blood or brutality
  • Has participated in a study < 30 days or a study such as this (i.e., experimental trauma) at all.

Sites / Locations

  • University of Zurich

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Dexmedetomidine

Gamma-hydroxybutyrate

Placebo

Arm Description

Sublingual dose of dexmedetomidine

Oral dose of gamma-hydroxybutyrate

Oral (saline) and sublingual (orodispersible tablet) doses

Outcomes

Primary Outcome Measures

Frequency of intrusive memories
The number of intrusive memories of the experimental model trauma film experienced. The number of intrusive memories will be recorded in a diary by participants.
Emotional valence of intrusive memories
The emotional valence will be recorded in a diary after experiencing an intrusive memory in an integer scale. The integer scale will range from 1 to 10, where 1 indicates the lowest and 10 indicates the highest.
Personal significance of intrusive memories
Personal significance of intrusive memories will be recorded in a diary after experiencing an intrusive memory in an integer scale. The integer scale will range from 1 to 10, where 1 indicates the lowest and 10 indicates the highest.
Oscillatory delta power in the sleep electroencephalogram (EEG) during non rapid eye movement (REM) sleep stages N2 and N3
Power in units microvolts squared will be quantified by fast Fourier transform in 4 second segment length in EEG sleep recordings in the delta frequency bin (0.5 - 4.5 Hz).Higher value of delta power indicates greater homeostatic sleep pressure, i.e., the feeling of need for sleep.
Oscillatory theta power in the sleep electroencephalogram (EEG) during non rapid eye movement sleep stages N2 and N3
Power in units microvolts squared will be quantified by fast Fourier transform in 4 second segment length in EEG sleep recordings in the theta frequency bin (6 - 9 Hz). Higher value of theta power indicates greater homeostatic sleep pressure, i.e., the feeling of need for sleep.
EEG measures of sleep quality: distribution of N2 and N3 sleep stages.
Number of non-REM sleep stages N2 and N3. Greater number of stages N2 and N3 indicate greater homeostatic sleep pressure, i.e., the feeling of need for sleep.
EEG measures of sleep quality: number of arousals
Number of arousals Arousals are defined by the American Academy of Sleep Medicine as an increase in EEG frequency at least 3 seconds in NREM sleep in alpha, theta or higher frequencies, excluding spindles; must be accompanied by a minimum of 1 second of muscle activity during REM sleep. The greater the number of arousals indicates the lower homeostatic sleep pressure is in healthy individuals. Normal number of arousals for a healthy adult is ca. 80 per 8 hour sleep episode.
EEG measures of sleep quality: sleep onset latency
Sleep onset latency represents elapsed time from intention to initiate sleep until sleep is initiated (defined as the occurrence of any stage of sleep by the AASM). Longer latencies indicate lower homeostatic sleep pressure or some maladaptive, e.g., rumination, stress, or pathological state, e.g., insomnia, posttraumatic stress. Normal latencies for healthy adults is 10 - 20 minutes.
EEG measures of sleep quality: sleep duration
Sleep duration represents the duration in time of a sleep episode excluding any intervening stages of waking. Typical sleep duration in the healthy adult population is ca. 8 hours. Extreme sleep durations (<5 or <6 hr or >10 hr) have been associated with cardiometabolic illness risk.
EEG measures of sleep quality: sleep efficiency
Sleep efficiency represents how efficient a given sleep episode is and is defined as the duration of sleep (i.e., time spent in all NREM and REM sleep stages) divided b by the total time spent in bed and multiplied by 100. Normal sleep efficiency is 80% or greater. Efficiencies less than this value could raise questions of sleep satiety, maladaptive behavior (e.g., alcohol consumption, caffeine consumption, sleep at incongruent circadian phase) or pathological health conditions (e.g., restless legs, disordered breathing, insomnia).

Secondary Outcome Measures

Physiological stress: circulating cortisol
Cortisol (nmol/l) is a marker of stress activation and will be quantified by salivary assay. Greater values indicate greater stress response. Salivary cortisol concentrations vary by sex; in males it ranges under normal conditions from 1-50 nmol/l.
Physiological stress: electrocardiogram (ECG) heart rate (HR)
Average resting ECG HR during waking in healthy adult males is 75 bpm (range: 60 - 100 bpm). Higher HR from an individual's baseline HR during and after experimental model trauma will be indicative of increases in sympathetic activation of heart function.
Physiological stress: respirometry respiration rate
Resting respiration rate of an adult male is 12 - 16 breaths per minute. Increases in the number of breaths per minute will indicate increase in sympathetic activation of the autonomic system.
Physiological stress: electrocardiogram (ECG) heart rate variability (HRV)
Heart rate variability will be quantified by measuring inter-beat intervals of the ECG. The normal-to-normal interval will be taken, which is the interpolated interval between normal R peaks of the QRS wave complex of the ECG. HRV values indicate performance of the autonomic nervous system in a given context. Higher values of sympathetic activation will be expected during experimental model trauma film exposure.
Physiological stress: inflammatory immune factors (cytokines and kynurenines)
Lower concentration values of immune factors will be expected in GHB or DMTN conditions compared to placebo conditions.
Subjective ratings of mood: Positive and Negative Affect Scale (PANAS)
The PANAS scale assesses affect and is comprised of a positive affect subscales and a negative affect subscale. The range of scores of either are 10 - 50. Higher scores in the positive subscale indicate higher (i.e., "better") mood; lower scores in the negative affect subscale indicate lower (i.e., "worse") mood. Mean (i.e., scores for normal healthy adults) respective scores for the positive and negative subscales are 33.3 (standard deviation [SD] = 7.2) and 17.4 (SD = 6.2).
Subjective ratings of mood: State Trait Anxiety Inventory (STAI)
The STAI assesses anxiety and is composed of a state and a trait scale. Scores in either can range from 20 - 80, and higher scores indicate greater anxiety. Mean scores for healthy adult males of the state and trait scales are, respectively 35.7 (SD = 10.4) and 34.9 (SD = 9.2).
Awakening response: cortisol
Salivary cortisol samples will be taken at regular intervals each morning in the lab to assess the awakening response. Higher values of cortisol concentrations indicate an stronger signal in this process of gaining alertness after sleep.
Awakening response: Psychomotor Vigilance Task (PVT)
To assess behavioral response to awaking after sleep, a simple 10 minute reaction time task at the computer called the PVT will be administered. Typical reaction times for an adult are < 500 ms from stimulus presentation. Higher values will be expected for greater degree of sleep inertia after awakening.
Sleep inertia Questionnaire - Acute (SIQ - Acute)
The SIQ - Acute assesses the subjective experience of the process of regaining alertness after waking from a sleep episode. Scores range from -66 to +66, higher scores indicating greater difficulty in regaining normal levels of alertness.

Full Information

First Posted
July 31, 2020
Last Updated
October 3, 2022
Sponsor
Psychiatric University Hospital, Zurich
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1. Study Identification

Unique Protocol Identification Number
NCT04508166
Brief Title
Towards a Post-exposition Pharmacological Prophylaxis for Post-traumatic Stress Disorder
Acronym
TRAUMA-PRO
Official Title
Pharmacological Prevention of Post-traumatic Intrusions in Healthy Volunteers - Towards a Post-exposition Prophylaxis for Post-traumatic Stress Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
October 1, 2021 (Actual)
Primary Completion Date
January 29, 2022 (Actual)
Study Completion Date
January 29, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Psychiatric University Hospital, Zurich

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this study, we investigate the role that deep sleep plays in the prevention of posttraumatic stress disorder after someone has been exposed to a trauma by boosting deep sleep with two drug conditions compared to placebo condition. Each volunteer in the study goes through all three conditions. The quantity of intrusive memories of the trauma will be compared between the three conditions.
Detailed Description
The present study seeks to investigate the potential to pharmacologically modulate slow-wave sleep in the acute aftermath of an experimentally-induced trauma in the interest of developing a secondary prevention of posttraumatic stress disorder. The effects of a GABAergic compound will be compared with that of a noradrenergic compound. Memory, sleep and stress-related immune response factors will be quantified and compared across drug conditions.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intrusive Thought, Psychological Trauma, Inflammatory Response, Physiological Stress

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dexmedetomidine
Arm Type
Experimental
Arm Description
Sublingual dose of dexmedetomidine
Arm Title
Gamma-hydroxybutyrate
Arm Type
Active Comparator
Arm Description
Oral dose of gamma-hydroxybutyrate
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Oral (saline) and sublingual (orodispersible tablet) doses
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine
Other Intervention Name(s)
Dexdor
Intervention Description
Volunteers receive a single dose of dexmedetomidine sublingually at scheduled bedrest in the sleep laboratory
Intervention Type
Drug
Intervention Name(s)
Gamma-Hydroxybutyrate
Other Intervention Name(s)
Xyrem
Intervention Description
Volunteers receive a single oral dose of gamma-hydroxybutyrate at scheduled bedrest in the sleep laboratory
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Volunteers receive an oral (saline) or sublingual (orodispersible tablet) at scheduled bedrest in the sleep laboratory
Intervention Type
Behavioral
Intervention Name(s)
Experimental Model Trauma Film
Intervention Description
Each volunteer views experimental model trauma film before scheduled bedrest in the sleep laboratory. This video is ca. 15 minutes in duration and is composed of short (a few seconds to a few minutes) individual and unrelated scenes of violent death and injury of varying description. Six versions of the film without re-occurring scenes will be presented in balanced order across drug order conditions.
Primary Outcome Measure Information:
Title
Frequency of intrusive memories
Description
The number of intrusive memories of the experimental model trauma film experienced. The number of intrusive memories will be recorded in a diary by participants.
Time Frame
Three weeks
Title
Emotional valence of intrusive memories
Description
The emotional valence will be recorded in a diary after experiencing an intrusive memory in an integer scale. The integer scale will range from 1 to 10, where 1 indicates the lowest and 10 indicates the highest.
Time Frame
Three weeks
Title
Personal significance of intrusive memories
Description
Personal significance of intrusive memories will be recorded in a diary after experiencing an intrusive memory in an integer scale. The integer scale will range from 1 to 10, where 1 indicates the lowest and 10 indicates the highest.
Time Frame
Three weeks
Title
Oscillatory delta power in the sleep electroencephalogram (EEG) during non rapid eye movement (REM) sleep stages N2 and N3
Description
Power in units microvolts squared will be quantified by fast Fourier transform in 4 second segment length in EEG sleep recordings in the delta frequency bin (0.5 - 4.5 Hz).Higher value of delta power indicates greater homeostatic sleep pressure, i.e., the feeling of need for sleep.
Time Frame
Four nights, each night a week apart, spanning one month
Title
Oscillatory theta power in the sleep electroencephalogram (EEG) during non rapid eye movement sleep stages N2 and N3
Description
Power in units microvolts squared will be quantified by fast Fourier transform in 4 second segment length in EEG sleep recordings in the theta frequency bin (6 - 9 Hz). Higher value of theta power indicates greater homeostatic sleep pressure, i.e., the feeling of need for sleep.
Time Frame
Four nights, each night a week apart, spanning one month
Title
EEG measures of sleep quality: distribution of N2 and N3 sleep stages.
Description
Number of non-REM sleep stages N2 and N3. Greater number of stages N2 and N3 indicate greater homeostatic sleep pressure, i.e., the feeling of need for sleep.
Time Frame
Four nights, each night a week apart, spanning one month
Title
EEG measures of sleep quality: number of arousals
Description
Number of arousals Arousals are defined by the American Academy of Sleep Medicine as an increase in EEG frequency at least 3 seconds in NREM sleep in alpha, theta or higher frequencies, excluding spindles; must be accompanied by a minimum of 1 second of muscle activity during REM sleep. The greater the number of arousals indicates the lower homeostatic sleep pressure is in healthy individuals. Normal number of arousals for a healthy adult is ca. 80 per 8 hour sleep episode.
Time Frame
Four nights, each night a week apart, spanning one month
Title
EEG measures of sleep quality: sleep onset latency
Description
Sleep onset latency represents elapsed time from intention to initiate sleep until sleep is initiated (defined as the occurrence of any stage of sleep by the AASM). Longer latencies indicate lower homeostatic sleep pressure or some maladaptive, e.g., rumination, stress, or pathological state, e.g., insomnia, posttraumatic stress. Normal latencies for healthy adults is 10 - 20 minutes.
Time Frame
Four nights, each night a week apart, spanning one month
Title
EEG measures of sleep quality: sleep duration
Description
Sleep duration represents the duration in time of a sleep episode excluding any intervening stages of waking. Typical sleep duration in the healthy adult population is ca. 8 hours. Extreme sleep durations (<5 or <6 hr or >10 hr) have been associated with cardiometabolic illness risk.
Time Frame
Four nights, each night a week apart, spanning one month
Title
EEG measures of sleep quality: sleep efficiency
Description
Sleep efficiency represents how efficient a given sleep episode is and is defined as the duration of sleep (i.e., time spent in all NREM and REM sleep stages) divided b by the total time spent in bed and multiplied by 100. Normal sleep efficiency is 80% or greater. Efficiencies less than this value could raise questions of sleep satiety, maladaptive behavior (e.g., alcohol consumption, caffeine consumption, sleep at incongruent circadian phase) or pathological health conditions (e.g., restless legs, disordered breathing, insomnia).
Time Frame
Four nights, each night a week apart, spanning one month
Secondary Outcome Measure Information:
Title
Physiological stress: circulating cortisol
Description
Cortisol (nmol/l) is a marker of stress activation and will be quantified by salivary assay. Greater values indicate greater stress response. Salivary cortisol concentrations vary by sex; in males it ranges under normal conditions from 1-50 nmol/l.
Time Frame
Four nights, each morning a week apart, spanning one month
Title
Physiological stress: electrocardiogram (ECG) heart rate (HR)
Description
Average resting ECG HR during waking in healthy adult males is 75 bpm (range: 60 - 100 bpm). Higher HR from an individual's baseline HR during and after experimental model trauma will be indicative of increases in sympathetic activation of heart function.
Time Frame
Four nights, each night a week apart, spanning one month
Title
Physiological stress: respirometry respiration rate
Description
Resting respiration rate of an adult male is 12 - 16 breaths per minute. Increases in the number of breaths per minute will indicate increase in sympathetic activation of the autonomic system.
Time Frame
Four nights, each night a week apart, spanning one month
Title
Physiological stress: electrocardiogram (ECG) heart rate variability (HRV)
Description
Heart rate variability will be quantified by measuring inter-beat intervals of the ECG. The normal-to-normal interval will be taken, which is the interpolated interval between normal R peaks of the QRS wave complex of the ECG. HRV values indicate performance of the autonomic nervous system in a given context. Higher values of sympathetic activation will be expected during experimental model trauma film exposure.
Time Frame
Four nights, each night a week apart, spanning one month
Title
Physiological stress: inflammatory immune factors (cytokines and kynurenines)
Description
Lower concentration values of immune factors will be expected in GHB or DMTN conditions compared to placebo conditions.
Time Frame
Four mornings, each morning a week apart, spanning one month
Title
Subjective ratings of mood: Positive and Negative Affect Scale (PANAS)
Description
The PANAS scale assesses affect and is comprised of a positive affect subscales and a negative affect subscale. The range of scores of either are 10 - 50. Higher scores in the positive subscale indicate higher (i.e., "better") mood; lower scores in the negative affect subscale indicate lower (i.e., "worse") mood. Mean (i.e., scores for normal healthy adults) respective scores for the positive and negative subscales are 33.3 (standard deviation [SD] = 7.2) and 17.4 (SD = 6.2).
Time Frame
Four nights, each night a week apart, spanning one month
Title
Subjective ratings of mood: State Trait Anxiety Inventory (STAI)
Description
The STAI assesses anxiety and is composed of a state and a trait scale. Scores in either can range from 20 - 80, and higher scores indicate greater anxiety. Mean scores for healthy adult males of the state and trait scales are, respectively 35.7 (SD = 10.4) and 34.9 (SD = 9.2).
Time Frame
Four nights, each night a week apart, spanning one month
Title
Awakening response: cortisol
Description
Salivary cortisol samples will be taken at regular intervals each morning in the lab to assess the awakening response. Higher values of cortisol concentrations indicate an stronger signal in this process of gaining alertness after sleep.
Time Frame
Four mornings, each morning a week apart, spanning one month
Title
Awakening response: Psychomotor Vigilance Task (PVT)
Description
To assess behavioral response to awaking after sleep, a simple 10 minute reaction time task at the computer called the PVT will be administered. Typical reaction times for an adult are < 500 ms from stimulus presentation. Higher values will be expected for greater degree of sleep inertia after awakening.
Time Frame
Four mornings, each morning a week apart, spanning one month
Title
Sleep inertia Questionnaire - Acute (SIQ - Acute)
Description
The SIQ - Acute assesses the subjective experience of the process of regaining alertness after waking from a sleep episode. Scores range from -66 to +66, higher scores indicating greater difficulty in regaining normal levels of alertness.
Time Frame
Four mornings, each morning a week apart, spanning one month

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Speaks and understands German BMI 18.5 -< 25 Non-smoker status Habitual 5 or fewer alcoholic beverages / week Habitual 3 or fewer caffeinated beverages / day Habitual average sleep duration 7-9 h / night Normal or corrected-to-normal vision Insomnia Severity Index score between 8-14 Exclusion Criteria: Travel across 3 or more time zones within 3 months of study start Habitual napping Extreme chronotype, determined by Morningness-Eveningness Questionnaire History of or presence of a trauma- or stressor-related disorder History of or presence of neurological disorder, psychiatric disorder or head injury History of or presence of a sleep disorder History of or presence of cardiovascular disorder Use of illicit drugs Atypical preference for excessively violent portrayals Faints at the site of blood or brutality Has participated in a study < 30 days or a study such as this (i.e., experimental trauma) at all.
Facility Information:
Facility Name
University of Zurich
City
Zürich
State/Province
Select An Option…
ZIP/Postal Code
8057
Country
Switzerland

12. IPD Sharing Statement

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Towards a Post-exposition Pharmacological Prophylaxis for Post-traumatic Stress Disorder

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