Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43870   clinical trials with a EudraCT protocol, of which   7289   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Early-life stress, the endocannabinoid system, and fear memory extinction

    Summary
    EudraCT number
    		 2017-004823-66
    Trial protocol
    		 NL  
    Global end of trial date
    08 Jul 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Jul 2022
    First version publication date
    16 Jul 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NL62274.091.17
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Radboud university medical center
    Sponsor organisation address
    P.O. Box 9101, Nijmegen, Netherlands, 6500 HB
    Public contact
    Dept Psychiatry Radboudumc, Radboudumc, +31 243613490, robbert-jan.verkes@radboudumc.nl
    Scientific contact
    Dept Psychiatry Radboudumc, Radboudumc, +31 243613490, robbert-jan.verkes@radboudumc.nl
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    08 Jul 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    08 Jul 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Jul 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Primary objective: Our key objective is to determine if glucocorticoid administration and/or THC administration facilitates fear memory extinction retention in an experimental model of exposure therapy in healthy individuals with early life stress.
    Protection of trial subjects
    After every screening session and at each end of the experimental session, we will conclude with a structured interview in which we will ask participants if they experience emotional disturbances triggered by the questions (e.g., regarding early-life trauma), at that moment or later, we can redirect them for additional help if needed. When participants are excluded from participation, we will carefully explain to them the reason for exclusion.
    Background therapy
    		 n.a.
    Evidence for comparator
    		 n.a.
    Actual start date of recruitment
    03 Oct 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 54
    Worldwide total number of subjects
    54
    EEA total number of subjects
    54
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    54
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The recruitment started on 03-10-2019 to 08-07-2021 and was in The Netherlands.

    Pre-assignment
    Screening details
    		 Healthy adults aged between 18-45 yrs old, gender-mixed, no illness, and current treatment. Participant were selected based presence or absence of a history of childhood trauma.

    Period 1
    Period 1 title
    Data collection (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    Both participants and researchers are blinded from the information of randomization .

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Childhood trauma group
    Arm description
    		 The participants were assigned to the traumatized group.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Hydrocortisone
    Investigational medicinal product code
    RVG 50730
    Other name
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    20mg hydrocortisone dissolved in juice.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    20mg undistinguishable placebo (cellulose) dispersed in juice.

    Arm title
    		 Control group
    Arm description
    		 The participants assigned to control group
    Arm type
    		 Experimental

    Investigational medicinal product name
    Hydrocortisone
    Investigational medicinal product code
    RVG 50730
    Other name
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    20mg hydrocortisone dispersed in the juice allowing affordable blinding of the study participants from treatment.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Oral liquid
    Routes of administration
    Oral use
    Dosage and administration details
    20mg undistinguishable placebo dispersed in the juice allowing affordable blinding of the study participants from treatment.

    Number of subjects in period 1
    		Childhood trauma group Control group
    Started
    27
    27
    Data collection finished
    27
    27
    Completed
    27
    27

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Data collection
    Reporting group description
    		 -

    Reporting group values
    		 Data collection Total
    Number of subjects
    		 54 54
    Age categorical
    There should be no differences of age between groups (with and without ELS)
    Units: Subjects
        Adults (18-64 years)
    		 54 54
    Gender categorical
    Gender was relatively balanced between groups (with and without ELS).
    Units: Subjects
        Female
    		 32 32
        Male
    		 22 22
    Subject analysis sets

    Subject analysis set title
    Drug effect on fear extinction retention
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The raw physiological data were converted and analyzed with an in-house tool in matlab. A repeated measures ANOVA was applied as a statistical model to check if the effect of hydrocortisone on fear extinction retention was equal or not in the traumatized group compared to control group.

    Subject analysis set title
    Drug effect on neural activity to autobiographical memory
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    To determine the effect of hydrocortisone on neural activity during emotional memory recall in the traumatized vs. control groups. The (functional) MRI data was preprocessed and analyzed in matlab 2021.

    Subject analysis sets values
    		 Drug effect on fear extinction retention Drug effect on neural activity to autobiographical memory
    Number of subjects
    52
    50
    Age categorical
    There should be no differences of age between groups (with and without ELS)
    Units: Subjects
        Adults (18-64 years)
    52
    50
    Age continuous
    Units:
        
    ±
    ±
    Gender categorical
    Gender was relatively balanced between groups (with and without ELS).
    Units: Subjects
        Female
    31
    30
        Male
    21
    20

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Childhood trauma group
    Reporting group description
    		 The participants were assigned to the traumatized group.

    Reporting group title
    Control group
    Reporting group description
    		 The participants assigned to control group

    Subject analysis set title
    Drug effect on fear extinction retention
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    The raw physiological data were converted and analyzed with an in-house tool in matlab. A repeated measures ANOVA was applied as a statistical model to check if the effect of hydrocortisone on fear extinction retention was equal or not in the traumatized group compared to control group.

    Subject analysis set title
    Drug effect on neural activity to autobiographical memory
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    To determine the effect of hydrocortisone on neural activity during emotional memory recall in the traumatized vs. control groups. The (functional) MRI data was preprocessed and analyzed in matlab 2021.

    Primary: Autonomic nervous system indices of the fear response and its recovery after extinction.

    		 Close Top of page
    End point title
    		 Autonomic nervous system indices of the fear response and its recovery after extinction.
    End point description
    Our primary endpoint is retention of safety learning in an experimental model of exposure therapy. This measure is operationalized as the magnitude of spontaneous recovery of differential autonomic nervous system reactivity (primarily indexed by skin conductance responses) to fear-conditioned stimuli (vs. control stimuli) one day after extinction (i.e., safety learning).
    End point type
    Primary
    End point timeframe
    Primary endpoint is measured 24 hrs after administration of the drug to assess drug effects on retention of safety learning.
    End point values
    		 Childhood trauma group Control group Drug effect on fear extinction retention
    Number of subjects analysed
    25
    27 [1]
    52
    Units: Skin conductance response magnitude
        arithmetic mean (standard error)
    -.20 ± .13
    .084 ± .17
    -.058 ± .11
    Notes
    [1] - data for two participants was lost due to technical failure
    Statistical analysis title
    		 Between-group comparison of drug effect
    Statistical analysis description
    Preliminary analysis of the difference in effect of hydrocortisone on retention of extinction memory in the childhood trauma versus control group
    Comparison groups
    Childhood trauma group v Control group
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    		 other [2]
    P-value
    		 = 0.2
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.15
         upper limit
    		 0.72
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.22
    Notes
    [2] - Test of an experimental effect.

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From 03-10-2019 to 08-07-2021, there were adverse events involving four participants.
    Adverse event reporting additional description
    Four adverse events were reported by participants. All procedures were terminated upon adverse events. Investigators followed standard procedures such as calming down and monitoring the participant, and following up the next day.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Childhood trauma group
    Reporting group description
    		 These are healthy volunteer participants selected for history of childhood trauma.

    Reporting group title
    Non-trauma control group
    Reporting group description
    		 These are healthy volunteer participants selected for absence of a history of childhoof trauma.

    Serious adverse events
    		 Childhood trauma group Non-trauma control group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 27 (0.00%)
    0 / 27 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Childhood trauma group Non-trauma control group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 27 (7.41%)
    2 / 27 (7.41%)
    Nervous system disorders
    Migraine
    Additional description: Participant complained of headache/migraine and therefore terminated participation in an MRI scan.
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Vertigo
    Additional description: One participant reported dizziness during blood sampling.
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Social circumstances
    Pain
    Additional description: As part of procedures, participant received mild electrical shock to the fingers. One participant reported discomfort during this procedure.
         subjects affected / exposed
    0 / 27 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Claustrophobia
    Additional description: One participant reported discomfort during MRI scanning because of confinement.
         subjects affected / exposed
    1 / 27 (3.70%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 Jul 2019
    Due to a substantial delay in the production of one of the study medications used in our study (THC tablets, produced by Echo Pharmaceuticals), we have decided to split our three-armed study design (placebo, hydrocortisone, THC) into two two-armed substudies (hydrocortisone versus placebo, THC versus placebo). This will allow us to start data acquisition for the hydrocortisone versus placebo substudy while waiting for the release of the THC tablets.
    08 Jul 2021
    The study was ended in May 2022 due to continuing delays in the production of one of the study medications used in our study (THC tablets, produced by Echo Pharmaceuticals). Therefore, only one of the two substudies (hydrocortisone versus placebo) has been completed, while the second substudy (THC versus placebo) cannot be conducted anymore.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    15 Mar 2020
    Due to the COVID-19 pandemic, we had to halt the study for 4 months.
    06 Jul 2020

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Due to the delay of THC providing, we split up the 2*3 study into two 2*2 substudies, namely there was no direct comparison between the effect of Hydrocortisone and THC on fear recall retention and relevant central neural activity.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue Apr 30 20:42:39 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA