Clinical Trial Results:
Boosting oxytocin after trauma: The effects of intranasal oxytocin administration on emotional and motivational brain processes in PTSD
Summary
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EudraCT number |
2012-001288-58 |
Trial protocol |
NL |
Global end of trial date |
19 May 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Jul 2021
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First version publication date |
12 Jul 2021
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Other versions |
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Summary report(s) |
OXT amygdala oxytocin amygdala connectivity oxytocin distraction oxytocin social reward oxytocin monetary reward |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
40122
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Amsterdam UMC, location Academic Medical Center
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Sponsor organisation address |
Meibergdreef 9, Amsterdam, Netherlands, 1105 AZ
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Public contact |
prof. dr. Miranda Olff, Amsterdam UMC, location Academic Medical Center, Academic Medical Center, Department of Psychiatru, +31 (0)208913662, m.olff@amc.uva.nl
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Scientific contact |
prof. dr. Miranda Olff, Amsterdam UMC, location Academic Medical Center, Department of Psychiatry, +31 (0)208913662, m.olff@amc.uva.nl
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
19 Mar 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 May 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
19 May 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
In this functional Magnetic Resonance Imaging (fMRI) study, the primary objective is to examine the acute effects of intranasal OT administration on emotional- and reward-related brain processes in PTSD patients compared to traumatized healthy controls. Furthermore, we aim to examine gender differences in the effects of intranasal OT administration on functional (task-specific) brain activation and in structural anatomy (i.e. volume and white matter integrity) between PTSD patients and traumatized healthy controls.
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Protection of trial subjects |
All study procedures were carried out in accordance with relevant laws and regulations.
All involved reseachers had received GCP training.
An independent monitor regularly monitored the RCT.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Jun 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 83
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Worldwide total number of subjects |
83
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EEA total number of subjects |
83
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
83
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||||||
Pre-assignment
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Screening details |
relevant details in terms of medication use: • Evidence of clinically significant and unstable medical conditions in which OT administration is contra-indicative • Use of: prostaglandins, anti-migraine medications (ergot alkaloids), ß-adrenergic receptor-blocking agents, systemic glucocorticoids and psychopharmacological medication. | |||||||||||||||||||||||||
Period 1
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Period 1 title |
Inclusion/baseline
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||
Roles blinded |
Investigator, Subject | |||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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PTSD women | |||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
oxytocin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal/oromucosal spray, solution
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Routes of administration |
Nasal use
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Dosage and administration details |
single adminstration of 40 IU
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Arm title
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PTSD men | |||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
oxytocin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal/oromucosal spray, solution
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Routes of administration |
Nasal use
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Dosage and administration details |
single adminstration of 40 IU
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Arm title
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Healthy control women | |||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||
Arm type |
healthy control | |||||||||||||||||||||||||
Investigational medicinal product name |
oxytocin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal/oromucosal spray, solution
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Routes of administration |
Nasal use
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Dosage and administration details |
single adminstration of 40 IU
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Arm title
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healthy control men | |||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||
Arm type |
healthy control group | |||||||||||||||||||||||||
Investigational medicinal product name |
oxytocin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal/oromucosal spray, solution
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Routes of administration |
Nasal use
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Dosage and administration details |
single adminstration of 40 IU
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 2 participants dropped out prior to randomization |
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Period 2
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Period 2 title |
2 fMRI sessions
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Is this the baseline period? |
No | |||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||||||
Blinding implementation details |
Medication allocation was concealed using a treatment code, only accessed by an independent researched who performed the randomization, made the randomization list and had no role in data collection . The study was conducted in a double-blinded way, in which both the participants and researchers involved in data collection were blind to treatment allocation. The treatment coding key remained concealed until data collection was completed unless in case of SAEs (NA in this trial).
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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PTSD women | |||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
oxytocin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal/oromucosal spray, solution
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Routes of administration |
Nasal use
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Dosage and administration details |
single adminstration of 40 IU
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Arm title
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PTSD men | |||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||
Investigational medicinal product name |
oxytocin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal/oromucosal spray, solution
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Routes of administration |
Nasal use
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Dosage and administration details |
single adminstration of 40 IU
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Arm title
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healthy control women | |||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||
Arm type |
healthy control group | |||||||||||||||||||||||||
Investigational medicinal product name |
oxytocin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal/oromucosal spray, solution
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Routes of administration |
Nasal use
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Dosage and administration details |
single adminstration of 40 IU
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Arm title
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healthy control men | |||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||
Arm type |
healthy control group | |||||||||||||||||||||||||
Investigational medicinal product name |
oxytocin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal/oromucosal spray, solution
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Routes of administration |
Nasal use
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Dosage and administration details |
single adminstration of 40 IU
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Notes [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: 1 participant dropped out prior to starting the mri sessions because of logistical reasons |
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Baseline characteristics reporting groups
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Reporting group title |
Inclusion/baseline
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
PTSD women
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Reporting group description |
- | ||
Reporting group title |
PTSD men
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Reporting group description |
- | ||
Reporting group title |
Healthy control women
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Reporting group description |
- | ||
Reporting group title |
healthy control men
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Reporting group description |
- | ||
Reporting group title |
PTSD women
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Reporting group description |
- | ||
Reporting group title |
PTSD men
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Reporting group description |
- | ||
Reporting group title |
healthy control women
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Reporting group description |
- | ||
Reporting group title |
healthy control men
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Reporting group description |
- |
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End point title |
amygdala connectivity | ||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
functional brain connectivity at the level of the right amygdala (CEM) with left vmPFC as measured during resting state during each scanning session, comparing activity during oxytocin to activity during placebo
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Statistical analysis title |
Difference OTvsPL | ||||||||||||||||||||
Statistical analysis description |
see Koch et al 2015 NPP
second-level repeated measures anovas with contrast estimates of positive correlations of ROIs with amygdala seeds, with between-subject factors PTSD status and SEX, and within subjects factor DRUG (OT vs PL), with drug order and mean framewise displacement added as covariate.
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Comparison groups |
PTSD women v healthy control women v PTSD men v healthy control men
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Number of subjects included in analysis |
71
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||||||||||
P-value |
< 0.05 [1] | ||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||
Confidence interval |
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Notes [1] - FWE corrected |
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Adverse events information
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Timeframe for reporting adverse events |
within 90 minutes after administration and one week after administration
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
2021AA
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Reporting groups
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Reporting group title |
PTSD patients after oxytocin
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PTSD patients after placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
controls after oxytocin
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
controls after placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 4% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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30 May 2012 |
added questionnaire on workrelated traumatic events |
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26 Oct 2012 |
collection of hair for cortisol assessment |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |