Clinical trial NCT04330677: Dissecting the Role of Estradiol in Mediating Gender-specific Anxiolytic and Prosocial Effects of Oxytocin
Official title: Dissecting the Role of Estradiol in Mediating Gender-specific Anxiolytic and Prosocial Effects of Oxytocin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Oxytocin
Estrogen
Fear Extinction
Emotion Processing
Memory
Keywords: fMRI
Oxytocin
Estrogen
Memory
Emotion Processing
Lead sponsor: University Hospital, Bonn
Sponsor class: OTHER
First posted: 2020-04-01
Enrollment: 487
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Electrodermal responses to fear-conditioned stimuli
timeFrame: 3 hours after gel administration and 30 minutes after nasal spray administration
measure: Emotion recognition thresholds
timeFrame: 200 minutes after gel administration and 50 minutes after nasal spray administration
measure: Resting state functional connectivity
timeFrame: 3 hours after gel administration and 30 minutes after nasal spray administration
measure: Neural responses to emotional faces
timeFrame: 190 minutes gel administration and 40 minutes after nasal spray administration
measure: Neural responses to an emotional subsequent memory task
timeFrame: 200 minutes after gel administration and 50 minutes after nasal spray administration
Secondary outcomes:
measure: Changes in oxytocin plasma concentration
timeFrame: 5 minutes before gel administration and 5 minutes after the last task
measure: Changes in estrogen plasma concentration
timeFrame: 5 minutes before gel administration and 5 minutes after the last task
measure: Contingency ratings of fear-conditioned stimuli
timeFrame: 3 hours after gel administration and 30 minutes after nasal spray administration
measure: Ultimatum game tasks
timeFrame: 150 minutes after gel administration
measure: Delayed discounting task
timeFrame: 170 minutes after gel administration
measure: Changes in the Multifaceted Empathy Test (MET)
timeFrame: 135 minutes after the gel administration on the fMRI acquisition day and three days after the fMRI acquisition day
measure: Changes in the Prisoner's Dilemma
timeFrame: 155 minutes after the gel administration on the fMRI acquisition day and three days after the fMRI acquisition day
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: Deparment of Psychiatry and Medical Psychology
Study officials:
affiliation: University of Oldenburg
name: Rene Hurlemann, MSc, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.