- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04330677
Dissecting the Role of Estradiol in Mediating Gender-specific Anxiolytic and Prosocial Effects of Oxytocin (ESMory)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The study comprises two subprojects (Study 1 and Study 2). In Study 1, the investigators will compare the effects of OXT on fear extinction and fear recall as well as on emotion recognition between women and men. Additionally, the investigators plan to test whether a pretreatment with exogenous estradiol can be used to augment these OXT effects. In Study 2, the investigators will use functional magnetic resonance imaging (fMRI) to elucidate the effects of OXT-estradiol interactions on neural responses in an emotional face matching task and an emotional memory task. Half of the participants will be included in Study 1 and the other half in Study 2.
Study 1 contains three test sessions (after the screening). In the first session participants will complete a fear conditioning paradigm. The second session will take place on the following day and will start with the administration of estradiol gel (Divigel; 2 mg) or placebo (PLC). Three hours after the gel administration the participants will intranasally self-administer 24 IU of OXT or PLC under supervision and 30 min later a fear extinction task will commence, followed by an emotion recognition paradigm. A fear extinction recall task (identical with the fear conditioning task except for the electric shocks) will be conducted in the third session (with a 24-hours break between the second and the third session).
In Study 2, participants will be randomly assigned to four different treatment conditions (1. OXT + PLC gel; 2. OXT + estradiol gel; 3. PLC + PLC gel; 4. PLC + estradiol gel) after the screening session. The timing of the drug administration and blood sample collection will be identical to that of the second session of Study 1. The fMRI paradigms (resting state, emotional face matching and emotional memory) will start 30 minutes after nasal spray administration. Three days after the scanning, participants will be tested with a surprise recognition task, which includes pictures shown in the scanner and distractors.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Bonn, Germany, 53105
- Deparment of Psychiatry and Medical Psychology
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- right handed
- healthy male & female volunteers
- women will be tested in their follicular phase (Day 0-5)
Exclusion Criteria:
- smoking
- pregnancy
- hormonal contraception
- current psychiatric illness
- current psychiatric medication or psychotherapy
- Study 2: MRI contraindication (e.g. metal in body, claustrophobia)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: RANDOMIZED
- Interventional Model: FACTORIAL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: 1. Oxytocin spray, 2. Estrogen gel
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Intranasal administration of 24 International Units, Oxytocin will be given 30 minutes before the fear extinction task (Study 1) or fMRI measurement (Study 2).
Participants received a single dose of estradiol gel (Estramon 2 mg estradiol, Hexal AG, Holzkirchen, Germany), applied to their shoulder, 3 hours prior to the fear extinction task (Study 1) or fMRI measurement (Study 2).
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EXPERIMENTAL: 1. Oxytocin spray, 2. Placebo gel
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Intranasal administration of 24 International Units, Oxytocin will be given 30 minutes before the fear extinction task (Study 1) or fMRI measurement (Study 2).
Participants received a single dose of the placebo gel (ultrasonic gel, 2 mg), applied to their shoulder, 3 hours prior to the fear extinction task (Study 1) or fMRI measurement (Study 2).
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EXPERIMENTAL: 1. Placebo spray, 2. Estrogen gel
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Participants received a single dose of estradiol gel (Estramon 2 mg estradiol, Hexal AG, Holzkirchen, Germany), applied to their shoulder, 3 hours prior to the fear extinction task (Study 1) or fMRI measurement (Study 2).
The placebo spray contains the identical ingredients, except for the peptide itself.
It will be given 30 minutes before the fear extinction task (Study 1) or fMRI measurement (Study 2).
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PLACEBO_COMPARATOR: 1. Placebo spray, 2. Placebo gel
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Participants received a single dose of the placebo gel (ultrasonic gel, 2 mg), applied to their shoulder, 3 hours prior to the fear extinction task (Study 1) or fMRI measurement (Study 2).
The placebo spray contains the identical ingredients, except for the peptide itself.
It will be given 30 minutes before the fear extinction task (Study 1) or fMRI measurement (Study 2).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Electrodermal responses to fear-conditioned stimuli
Time Frame: 3 hours after gel administration and 30 minutes after nasal spray administration
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In Study 1, electrodermal responses will be measured during the fear conditioning and fear extinction tasks.
The paradigm is an adapted version of a validated fear-conditioning procedure.
Before the start of the paradigm a baseline of electrodermal activity is recorded for 60 seconds.
During the conditioning session four neutral conditioned stimuli (two CS+ A and two CS+ B) are paired with an aversive US (electric shock) in 75 % contingency, whereas two other neutral stimuli are never paired with the US (non-fear-associated stimulus [CS-]).
In CS+ trials electric shocks are administered during the last 500 milliseconds of the trial.
In the fear extinction session all CS+ and CS- are presented in the absence of electric shocks.
Oxytocin and estradiol baseline concentrations will be tested as moderator variables.
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3 hours after gel administration and 30 minutes after nasal spray administration
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Emotion recognition thresholds
Time Frame: 200 minutes after gel administration and 50 minutes after nasal spray administration
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In Study 1, emotion recognition will be measured.
During the emotion recognition task, emotional faces are presented and participants are required to indicate the perceived emotion ("neutral", "fearful", "happy", "disgusted", "angry", "not sure") in a following self-paced phase.
A Bayesian adaptive procedure ("QUEST") will be used to determine the stimulus presentation and to estimate individual emotion thresholds.
Oxytocin and estradiol baseline concentrations will be tested as moderator variables.
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200 minutes after gel administration and 50 minutes after nasal spray administration
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Resting state functional connectivity
Time Frame: 3 hours after gel administration and 30 minutes after nasal spray administration
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In Study 2, resting state functional connectivity will be measured.
The resting state fMRI analysis will focus on functional connectivity between regions-of-interest (ROIs) associated with emotional processing (i.e.
amygdala, cingulate and prefrontal cortex, insula, striatal areas).
Oxytocin and estradiol baseline concentrations will be tested as moderator variables.
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3 hours after gel administration and 30 minutes after nasal spray administration
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Neural responses to emotional faces
Time Frame: 190 minutes gel administration and 40 minutes after nasal spray administration
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In Study 2, neural responses to emotional faces will be measured.
Functional magnetic resonance imaging will be performed to measure the blood-oxygen-level dependent signal in response to emotional faces.
Analyses will focus on regions-of-interest associated with emotional processing (i.e.
amygdala, cingulate and prefrontal cortex, insula, striatal areas).
Oxytocin and estradiol baseline concentrations will be tested as moderator variables.
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190 minutes gel administration and 40 minutes after nasal spray administration
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Neural responses to an emotional subsequent memory task
Time Frame: 200 minutes after gel administration and 50 minutes after nasal spray administration
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In Study 2, neural responses to an emotional subsequent memory task will be measured.
Functional magnetic resonance imaging will be performed to measure the blood-oxygen-level dependent signal in response to emotional scenes.
The investigators plan to analyze scenes depending on valence (positive, negative, neural) and sociality (social, non-social).
Furthermore, remembered and non-remembered emotional pictures will be compared.
To classify pictures as remembered and non-remembered, participants will perform a memory recognition task three days after the MRI scan.
The recognition task will include pictures shown in the scanner and distractors.
Analyses will focus on regions-of-interest associated with emotional processing and memory (i.e.
amygdala, hippocampus, cingulate and prefrontal cortex, insula, striatal areas).
Oxytocin and estradiol baseline concentrations will be tested as moderator variables.
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200 minutes after gel administration and 50 minutes after nasal spray administration
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in oxytocin plasma concentration
Time Frame: 5 minutes before gel administration and 5 minutes after the last task
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In both studies, blood samples will be collected 5 minutes before gel administration and 5 minutes after the last task.
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5 minutes before gel administration and 5 minutes after the last task
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Changes in estrogen plasma concentration
Time Frame: 5 minutes before gel administration and 5 minutes after the last task
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In both studies, blood samples will be collected 5 minutes before gel administration and 5 minutes after the last task.
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5 minutes before gel administration and 5 minutes after the last task
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Contingency ratings of fear-conditioned stimuli
Time Frame: 3 hours after gel administration and 30 minutes after nasal spray administration
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In Study 1, during the first 3500 ms of a trial in the fear conditioning and fear extinction tasks participants will be required to indicate via button press whether they expect to receive an electric shock (yes, no, not sure).
Oxytocin and estradiol baseline concentrations will be tested as moderator variables.
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3 hours after gel administration and 30 minutes after nasal spray administration
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Ultimatum game tasks
Time Frame: 150 minutes after gel administration
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In Study 1, bargaining behavior will be measured in three different versions of the Ultimatum Game (restricted, unrestricted and computer ultimatum game).
All participants will play as responders in the three versions.
As a cover story, participants will be told that they play against real partners, who took part in previous experiments.
In the restricted version of the Ultimatum Game, the proposer can only decide between two given options.
As such, chosen offers are either framed as fair or unfair depending on the alternative option.
In the unrestricted Ultimatum Game, the proposer can freely decide how to split 10 Euro.
In addition, participants will complete 24 trials of a computer version of the unrestricted Ultimatum Game, in which the word "computer" will be shown instead of a picture of the proposer.
Estradiol baseline concentrations will be tested as moderator variables.
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150 minutes after gel administration
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Delayed discounting task
Time Frame: 170 minutes after gel administration
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In Study 1, subjects will perform a delayed discounting task in order to assess their control of impulsive preferences.
Participants will be asked to choose between small immediate rewards and larger later rewards.
Estradiol baseline concentrations will be tested as moderator variables.
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170 minutes after gel administration
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Changes in the Multifaceted Empathy Test (MET)
Time Frame: 135 minutes after the gel administration on the fMRI acquisition day and three days after the fMRI acquisition day
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In Study 2, participants' empathy will be assessed with the Multifaceted Empathy Test (MET) which includes photographs showing people in emotionally charged situations.
Participants will be asked to infer the mental states of the individuals shown (cognitive empathy) and to rate their emotional response to the picture (emotional empathy).
Participants will perform the MET twice: 1. before the fMRI in the second session and and 2. three days following the fMRI.
Estradiol baseline concentrations will be tested as moderator variables.
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135 minutes after the gel administration on the fMRI acquisition day and three days after the fMRI acquisition day
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Changes in the Prisoner's Dilemma
Time Frame: 155 minutes after the gel administration on the fMRI acquisition day and three days after the fMRI acquisition day
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In Study 2, the investigators will use an iterated version of the prisoner's dilemma to evaluate the participant's cooperative behavior.
The participants will have to decide multiple times whether they want to betray their opponent or whether they choose to cooperate.
Participants will perform the Prisoner's Dilemma twice: 1. before the fMRI in the second session and and 2. three days following the fMRI.Estradiol baseline concentrations will be tested as moderator variables.
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155 minutes after the gel administration on the fMRI acquisition day and three days after the fMRI acquisition day
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Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ESMory
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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