Impact of Estrogen on Fear Extinction R61

The Influence of Estrogen on the Fear Extinction Network in Humans-R61

The goal of this project is to examine how estrogen may influence the resting-state connectivity and the extinction-induced activation of the fear extinction network.

Study Overview

• Status: Completed
• Conditions: Fear; Fear; Examination, Phobic
• Intervention / Treatment: Drug: Estradiol 2Mg Tablet; Drug: Estradiol 4Mg Tablet; Drug: Placebo Pills

Detailed Description

The aim of the study was to examine the influence of exogenous estrogen administration on the activation of the fear extinction network in women. Functional MRI data and psychophysiological indices were collected to test the influence of estrogen on women's ability to regulate conditioned fear responses. Women underwent a 3 day experimental paradigm using classical fear conditioning. The first day was conducted outside the scanner, while days 2 and 3 were done inside the fMRI scanner and tested fear extinction learning and recall in days 2 and 3, respectively. The estrogen (or placebo) pill was given just hours before extinction learning test on day 2. No followups were conducted after women completed the 3 day study.

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Right-handed (Edinburgh Inventory - Oldfield 1971).
• SCID diagnosis consistent with none, current or past history of Axis I psychiatric disorders.
• To be matched for age, gender, and years of education, as well as self-identified race/ethnicity.
• For naturally cycling female subjects, stage of menstrual cycle will be ascertained by history, and by serological measures.
• For women on oral contraceptives, we will identify those using 20mcg ethinyl, 2nd or 3rd generation, monophasic

Exclusion Criteria:

• Psychiatric, neurologic or medical condition that would interfere with study procedures or confound results, ascertained by history.
• History of seizure or significant head trauma (i.e., extended loss of consciousness, neurological sequelae, or known structural brain lesion).
• History of Axis I psychiatric diagnosis; e.g., history of substance use disorder, psychotic disorder, bipolar disorder, tic disorder, or eating disorder.
• Use of psychotropic medication within 4 weeks prior to study (within 6 weeks for fluoxetine, or other long-lived compounds; within one year for neuroleptics).
• Pregnancy (to be ruled out by urine ß-HCG).
• Metallic implants or devices contraindicating magnetic resonance imaging.
• Use of oral contraceptives or non-oral contraceptives containing estrogen and progesterone within 3 months
• History of breast cancer.
• Allergy to peanut oil.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Estradiol 2mg Dose; 2mg dose of estradiol (oral administration)	Drug: Estradiol 2Mg Tablet; one 2 mg dose of estradiol (obtained from Estrace® Tablets, 2.0 mg estradiol tablets, USP, Warner Chilcott),; Other Names: Estrace® Tablets
Experimental: Estradiol 4mg Dose; 4mg dose of estradiol (oral administration)	Drug: Estradiol 4Mg Tablet; two 2 mg pills estradiol(obtained from Estrace® Tablets, 2.0 mg estradiol tablets, USP, Warner Chilcott),; Other Names: Estrace® Tablets
Placebo Comparator: Placebo; placebo (oral administration)	Drug: Placebo Pills; inactive placebo pills; Other Names: Estrace® Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of exogenous administration of estradiol on the neural correlates of fear extinction	BOLD responses during fear extinction after taking estradiol or placebo	3 Days

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Mohammed Milad, PhD, NYU School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Actual): April 15, 2019
• Study Completion (Actual): April 15, 2019

Study Registration Dates

• First Submitted: January 26, 2016
• First Submitted That Met QC Criteria: February 1, 2016
• First Posted (Estimate): February 4, 2016

Study Record Updates

• Last Update Posted (Actual): July 30, 2020
• Last Update Submitted That Met QC Criteria: July 29, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Estradiol; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: 2007P000496

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No