Perimenopausal Effects of Estradiol on Reward Responsiveness

NCT02255175 | Completed Phase 4 Results

• 3 other identifiers: 13-3572K12HD001441-15K23MH105569-01A1
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

Using neuroimaging, the investigator will study the effects of estrogen on mood and brain function in perimenopausal women either with or without depression.

Conditions

Perimenopausal Depression

Keywords

Reproductive Affective Disorder; Depression; Perimenopause; Estrogen; Estradiol treatment; Mood Disorders; Estrogen Replacement Therapy; Sex Steroids; Depressive disorder; Mental Disorders; Estradiol; Hormones; Physiological effects of drugs; Reproductive Control Agents

Outcome Measures

Primary Outcomes (6)

• Caudate Signal Intensity in Response to Reward During the MID fMRI Task at Pre-treatment

  Caudate reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups at pre-treatment.

  Pre-treatment (visit 3)

• Nucleus Accumbens (NAcc) Signal Intensity in Response to Reward During the MID fMRI Task at Pre-treatment

  Nucleus Accumbens (NAcc) reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups at pre-treatment.

  Pre-treatment (visit 3)

• Putamen Signal Intensity in Response to Reward During the MID fMRI Task at Pre-treatment

  Putamen reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups at pre-treatment.

  Pre-treatment (visit 3)

• Caudate Signal Intensity in Response to Reward During the MID fMRI Task Following Estradiol Treatment.

  Caudate reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups following treatment.

  Post-treatment (visit 6)

• Nucleus Accumbens (NAcc) Signal Intensity in Response to Reward During the MID fMRI Task Following Estradiol Treatment.

  Nucleus accumbens (NAcc) reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups following treatment.

  Post-treatment (visit 6)

• Putamen Signal Intensity in Response to Reward During the MID fMRI Task Following Estradiol Treatment.

  Putamen reactivity to reward during the Monetary Incentive Delay (MID) task was measured between the two groups. During MID the task, participants respond to "win" trials by pressing a button on a button box in the MRI as quickly as possible when the see a target. Reactivity is measured by examining participant's change in blood-oxygen-level dependent (BOLD) (i.e., measurement of oxygen level that is carried to neurons by red blood cells since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen) in response to a stimulus of interest (win trials) versus non-stimulus (non-win trials). Percent signal change in BOLD activation between monetary reward versus non-reward is the outcome of interest. Percent signal change is then compared between the two groups following treatment.

  Post-treatment (visit 6)

Secondary Outcomes (3)

• Response Latency to Reward During the MID fMRI Task at Pre-treatment

  Pre-treatment (visit 3)

• Response Latency to Reward During the MID fMRI Task Following Estradiol Treatment

  Post-treatment (visit 6)

• Change in Inventory of Depression and Anxiety Symptoms (IDAS) Dysphoria Scores

  Assessed at pre- and post-treatment (visits 3 and 6)

Study Arms (2)

Perimenopausal women, depressed

EXPERIMENTAL

Participants will receive transdermal estradiol (100μg/day) for 3 weeks. Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation.

Drug: Estradiol; Drug: Progesterone

Perimenopausal women, non-depressed

ACTIVE COMPARATOR

Participants will receive transdermal estradiol (100μg/day) for 3 weeks. Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation.

Drug: Estradiol; Drug: Progesterone

Interventions

Estradiol DRUG

Participants will receive transdermal estradiol (100μg/day) for 3 weeks

Also known as: Transdermal estradiol, Climara

Perimenopausal women, depressed; Perimenopausal women, non-depressed

Progesterone DRUG

Participants will receive an additional week of combined estradiol and micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation.

Also known as: Prometrium, Micronized progesterone

Perimenopausal women, depressed; Perimenopausal women, non-depressed

Eligibility Criteria

• Age: 44 Years - 55 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• MDD Group Eligibility Criterion: current diagnosis of MDD with an onset associated with menstrual cycle irregularity, and no history of psychiatric illness during the 2 years before the onset of the current depressive episode as determined by the Structured Clinical Interview for DSM-IV-TR (Diagnostic and Statistical Manual-4-Text Revision) for Axis I Disorders (SCID);
• Control Group Eligibility Criterion: absence of any past or present psychiatric disorder as assessed by the SCID.
• Patients will not be permitted to enter this protocol if they have any of the following:
• current medication use (i.e., psychotropics, anti-hypertensives, statins, hormonal preparations, or frequent use of anti-inflammatory agents (\> 10 times/month)). Women will be allowed to enroll who take medications without known mood effects (e.g. stable thyroid hormone replacement and occasional (\< 5 times/month) use of Ambien)\*;
• pregnant, breastfeeding or trying to conceive;
• FMP more than 12 months prior to enrollment;
• history of undiagnosed vaginal bleeding;
• undiagnosed enlargement of the ovaries;
• polycystic ovary syndrome;
• history of breast or ovarian cancer;
• first degree relative with ovarian cancer;
• first degree relative with premenopausal onset or bilateral breast cancer;
• + first degree relatives with breast cancer (regardless of onset);
• + relatives with postmenopausal breast cancer;
• abnormal finding in a provider breast exam and/or mammogram;

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

MeSH Terms

Conditions

Depression; Mood Disorders; Depressive Disorder; Mental Disorders

Interventions

Estradiol; Progesterone

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnenediones; Pregnenes; Pregnanes; Corpus Luteum Hormones; Progesterone Congeners

Results Point of Contact

• Title: Crystal Edler Schiller, PhD
• Organization: UNC School of Medicine

crystal_schiller@med.unc.edu

919-966-4810

Study Officials

• Crystal Schiller, PhD

  University of North Carolina at Chapel Hill Psychiatry Department

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2014
• First Posted: October 2, 2014
• Study Start: October 1, 2015
• Primary Completion: October 17, 2018
• Study Completion: October 17, 2018
• Last Updated: November 12, 2019
• Results First Posted: November 12, 2019

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)