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

University Hospital Bonn (UKB)

Status and phase: Completed; Phase 1

Conditions: Emotion Processing; Estrogen; Fear Extinction; Memory; Oxytocin

Treatments: Drug: Estrogen Gel; Drug: Oxytocin nasal spray; Drug: Placebo nasal spray; Drug: Placebo Gel

Study type: Interventional

Funder types: Other

Identifiers

NCT04330677

ESMory

Details and patient eligibility

About

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.

Full 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.

Enrollment: 487 patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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487 participants in 4 patient groups, including a placebo group

1. Oxytocin spray, 2. Estrogen gel

Experimental group

Treatment:

Drug: Estrogen Gel

Drug: Oxytocin nasal spray

1. Oxytocin spray, 2. Placebo gel

Experimental group

Treatment:

Drug: Placebo Gel

Drug: Oxytocin nasal spray

1. Placebo spray, 2. Estrogen gel

Experimental group

Treatment:

Drug: Estrogen Gel

Drug: Placebo nasal spray

1. Placebo spray, 2. Placebo gel

Placebo Comparator group

Treatment:

Drug: Placebo nasal spray

Drug: Placebo Gel