Dissecting the Role of Estradiol in Mediating Gender-specific Anxiolytic and Prosocial Effects of Oxytocin

NCT04330677 | Completed Phase 1

• 1 other identifier: ESMory
• Study Type: interventional
• Target: 487
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to examine a behavioral and neural framework for understanding the sex-specific effects of the neuropeptide oxytocin (OXT). Using hormonal, behavioral and neuroimaging readouts, it is planned to explore the interplay of OXT and estradiol as a potential mechanism mediating sexual dimorphic effects.

Conditions

Oxytocin; Estrogen; Fear Extinction; Emotion Processing; Memory

Keywords

fMRI; Oxytocin; Estrogen; Memory; Emotion Processing

Outcome Measures

Primary Outcomes (5)

• Electrodermal responses to fear-conditioned stimuli

  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.

  3 hours after gel administration and 30 minutes after nasal spray administration

• Emotion recognition thresholds

  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.

  200 minutes after gel administration and 50 minutes after nasal spray administration

• Resting state functional connectivity

  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.

  3 hours after gel administration and 30 minutes after nasal spray administration

• Neural responses to emotional faces

  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.

  190 minutes gel administration and 40 minutes after nasal spray administration

• Neural responses to an emotional subsequent memory task

  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.

  200 minutes after gel administration and 50 minutes after nasal spray administration

Secondary Outcomes (7)

• Changes in oxytocin plasma concentration

  5 minutes before gel administration and 5 minutes after the last task

• Changes in estrogen plasma concentration

  5 minutes before gel administration and 5 minutes after the last task

• Contingency ratings of fear-conditioned stimuli

  3 hours after gel administration and 30 minutes after nasal spray administration

• Ultimatum game tasks

  150 minutes after gel administration

• Delayed discounting task

  170 minutes after gel administration

Study Arms (4)

1. Oxytocin spray, 2. Estrogen gel

EXPERIMENTAL

Drug: Oxytocin nasal spray; Drug: Estrogen Gel

1. Oxytocin spray, 2. Placebo gel

EXPERIMENTAL

Drug: Oxytocin nasal spray; Drug: Placebo Gel

1. Placebo spray, 2. Estrogen gel

EXPERIMENTAL

Drug: Placebo nasal spray; Drug: Estrogen Gel

1. Placebo spray, 2. Placebo gel

PLACEBO COMPARATOR

Drug: Placebo nasal spray; Drug: Placebo Gel

Interventions

Oxytocin nasal spray DRUG

Intranasal administration of 24 International Units, Oxytocin will be given 30 minutes before the fear extinction task (Study 1) or fMRI measurement (Study 2).

1. Oxytocin spray, 2. Estrogen gel; 1. Oxytocin spray, 2. Placebo gel

Placebo nasal spray DRUG

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).

1. Placebo spray, 2. Estrogen gel; 1. Placebo spray, 2. Placebo gel

Estrogen Gel DRUG

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).

1. Oxytocin spray, 2. Estrogen gel; 1. Placebo spray, 2. Estrogen gel

Placebo Gel DRUG

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).

1. Oxytocin spray, 2. Placebo gel; 1. Placebo spray, 2. Placebo gel

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• right handed
• healthy male \& female volunteers
• women will be tested in their follicular phase (Day 0-5)

You may not qualify if:

• smoking
• pregnancy
• hormonal contraception
• current psychiatric illness
• current psychiatric medication or psychotherapy
• Study 2: MRI contraindication (e.g. metal in body, claustrophobia)

Sponsors & Collaborators

• University Hospital, Bonn: lead

Study Sites (1)

Deparment of Psychiatry and Medical Psychology

Bonn, 53105, Germany

Location

Related Publications (1)

• Hariri AR, Tessitore A, Mattay VS, Fera F, Weinberger DR. The amygdala response to emotional stimuli: a comparison of faces and scenes. Neuroimage. 2002 Sep;17(1):317-23. doi: 10.1006/nimg.2002.1179.

  PMID: 12482086 BACKGROUND

Related Links

• Neuromodulation of Emotion (NEMO) research group

Study Officials

• Rene Hurlemann, MSc, MD, PhD

  University of Oldenburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor for Psychiatry

Study Record Dates

• First Submitted: March 30, 2020
• First Posted: April 1, 2020
• Study Start: September 18, 2016
• Primary Completion: January 25, 2020
• Study Completion: January 25, 2020
• Last Updated: April 7, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)