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

NCT ID: NCT04330677

Last Updated: 2020-04-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 487 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-18
• Study Completion Date: 2020-01-25

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.

Conditions

Oxytocin; Estrogen; Fear Extinction; Emotion Processing; Memory

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

1. Oxytocin spray, 2. Estrogen gel

Group Type: EXPERIMENTAL

Oxytocin nasal spray

Intervention Type: 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).

Estrogen Gel

Intervention Type: 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. Placebo gel

Group Type: EXPERIMENTAL

Oxytocin nasal spray

Intervention Type: 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).

Placebo Gel

Intervention Type: 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. Placebo spray, 2. Estrogen gel

Group Type: EXPERIMENTAL

Placebo nasal spray

Intervention Type: 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).

Estrogen Gel

Intervention Type: 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. Placebo spray, 2. Placebo gel

Group Type: PLACEBO_COMPARATOR

Placebo nasal spray

Intervention Type: 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).

Placebo Gel

Intervention Type: 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).

Interventions

Oxytocin nasal spray

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

Intervention Type: DRUG

Placebo nasal spray

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).

Intervention Type: DRUG

Estrogen Gel

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).

Intervention Type: DRUG

Placebo Gel

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).

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Bonn

OTHER

Sponsor Role: lead

Responsible Party

Rene Hurlemann

Professor for Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rene Hurlemann, MSc, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Oldenburg

Locations

Deparment of Psychiatry and Medical Psychology

Bonn, , Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 12482086 (View on PubMed)

Related Links

http://renehurlemann.squarespace.com/welcome/

Neuromodulation of Emotion (NEMO) research group

Other Identifiers

ESMory

Identifier Type: -

Identifier Source: org_study_id