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

NCT04508166 | Completed DMC

• 1 other identifier: TRAUMA-PROPHYLAXIS
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Intrusive Thought; Psychological Trauma; Inflammatory Response; Physiological Stress

Outcome Measures

Primary Outcomes (10)

• 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.

  Three weeks

• 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.

  Three weeks

• 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.

  Three weeks

• 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.

  Four nights, each night a week apart, spanning one month

• 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.

  Four nights, each night a week apart, spanning one month

• 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.

  Four nights, each night a week apart, spanning one month

• 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.

  Four nights, each night a week apart, spanning one month

• 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.

  Four nights, each night a week apart, spanning one month

• 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.

  Four nights, each night a week apart, spanning one month

• 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).

  Four nights, each night a week apart, spanning one month

Secondary Outcomes (10)

• Physiological stress: circulating cortisol

  Four nights, each morning a week apart, spanning one month

• Physiological stress: electrocardiogram (ECG) heart rate (HR)

  Four nights, each night a week apart, spanning one month

• Physiological stress: respirometry respiration rate

  Four nights, each night a week apart, spanning one month

• Physiological stress: electrocardiogram (ECG) heart rate variability (HRV)

  Four nights, each night a week apart, spanning one month

• Physiological stress: inflammatory immune factors (cytokines and kynurenines)

  Four mornings, each morning a week apart, spanning one month

Study Arms (3)

Dexmedetomidine

EXPERIMENTAL

Sublingual dose of dexmedetomidine

Drug: Dexmedetomidine; Drug: Placebo; Behavioral: Experimental Model Trauma Film

Gamma-hydroxybutyrate

ACTIVE COMPARATOR

Oral dose of gamma-hydroxybutyrate

Drug: Gamma-Hydroxybutyrate; Drug: Placebo; Behavioral: Experimental Model Trauma Film

Placebo

PLACEBO COMPARATOR

Oral (saline) and sublingual (orodispersible tablet) doses

Drug: Dexmedetomidine; Drug: Placebo; Behavioral: Experimental Model Trauma Film

Interventions

Dexmedetomidine DRUG

Volunteers receive a single dose of dexmedetomidine sublingually at scheduled bedrest in the sleep laboratory

Also known as: Dexdor

Dexmedetomidine; Placebo

Gamma-Hydroxybutyrate DRUG

Volunteers receive a single oral dose of gamma-hydroxybutyrate at scheduled bedrest in the sleep laboratory

Also known as: Xyrem

Gamma-hydroxybutyrate

Placebo DRUG

Volunteers receive an oral (saline) or sublingual (orodispersible tablet) at scheduled bedrest in the sleep laboratory

Dexmedetomidine; Gamma-hydroxybutyrate; Placebo

Experimental Model Trauma Film BEHAVIORAL

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.

Dexmedetomidine; Gamma-hydroxybutyrate; Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Psychiatric University Hospital, Zurich: lead

Study Sites (1)

University of Zurich

Zurich, Select An Option…, 8057, Switzerland

Location

MeSH Terms

Conditions

Psychological Trauma

Interventions

Dexmedetomidine; Sodium Oxybate

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydroxybutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2020
• First Posted: August 11, 2020
• Study Start: October 1, 2021
• Primary Completion: January 29, 2022
• Study Completion: January 29, 2022
• Last Updated: October 4, 2022

Record last verified: 2022-10

Locations

CH (1)