RECRUITING

Examining the Effects of Estradiol on Neural and Molecular Response to Reward

Conditions

Depression Psychosis Anhedonia Reproductive Affective Disorder Perimenopause Estrogen Hormone Replacement Therapy Mood Disorders Estradiol Treatment Sex Steroids Psychosis Symptoms Depressive Disorders Estradiol Hormones Reward Activation Reproductive Control Agents

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This proposal will examine the effects of estradiol administration on perimenopausal-onset (PO) anhedonia and psychosis symptoms as well as on brain function using simultaneous positron emission tomography and functional magnetic resonance imaging (PET-MR).

Official Title

Examining the Effects of Estradiol on Neural and Molecular Response to Rewards in Perimenopausal-Onset Anhedonia and Psychosis

Quick Facts

Study Start:2022-04-20

Study Completion:2026-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05282277

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:45 Years to 55 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
* Provision of signed and dated informed consent form * Stated willingness to comply with all study procedures, lifestyle considerations, and availability for the duration of the study * 44-55 years old unmedicated perimenopausal women who have ≥ 2 skipped menstrual cycles, amenorrhea ≥ 60 days, corresponding to the late menopause transition (Stages of Reproductive Aging Workshop (STRAW stage -1). * Anhedonia or psychosis symptoms that began during the period of menstrual irregularity. * Clinician's Global Impression Scale-Severity score (CGI-S) \> 3 to confirm a clinically impaired sample. * Anhedonia severity inclusion criteria and stratification: All participants will have Snaith-Hamilton Pleasure Scale (SHAPS) scores \> 20 consistent with the NIMH Fast-Fail Trial for Mood and Anxiety Disorders, corresponding to clinically impairing anhedonia. * Psychosis severity inclusion criteria and stratification: Participants will be stratified according to scores on the psychotic subscale of the Brief Psychiatric Rating Scale (BPRS) * Willingness to adhere to the estradiol regimen	* Pregnancy; allergies to any active or inactive ingredients in the Climara® patch or Prometrium®. * BMI \< 18 or \> 35 kg/m\^2 * A history of chronic menstrual cycle irregularity, meaning \> 1 year without menses * MR contraindications: Metal in the body, dental work other than fillings or gold, tattoos, metal injury, any other implant unless they are 100% plastic. * PET contradictions: participation in \>1 research study in the past 12 months that included ionizing radiation exceeding 3 rem to the whole body (e.g., PET, CT). Standard of care imaging is not exclusionary. * The use of psychotropics or hormonal preparations. * History of psychiatric illness during the 2 years before the onset of perimenopause. * History of chronic, recurrent mood or psychotic disorders (i.e., more than one non-reproductive-related mood episode prior to the perimenopausal index episode). * A history of mood episodes requiring hospitalization. * Current mania; * Depressive episode(s) within 2 years of enrollment not associated with the transition to menopause; * A history of suicide attempts within the last year or current active suicidal ideation with intent and plan. * Neurological conditions (e.g., history of seizure or TBI) * Brain stimulation treatment in the past six months. * Endometriosis; * First degree relative with premenopausal breast cancer or breast cancer presenting in both breasts or multiple family members (greater than three relatives) with postmenopausal breast cancer. * Current medication use (i.e., current psychotropics, current anti-hypertensives, current statins, current 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; * Last menstrual period 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; * Abnormal finding in a provider breast exam and/or mammogram; * Known carrier of BRCA1 or 2 mutation; * Porphyria; * Malignant melanoma; * Hodgkin's disease; * Recurrent migraine headaches that are preceded by aura; * Gallbladder or pancreatic disease\\; * Heart or kidney disease\\; * Liver disease; * cerebrovascular disease (stroke); * First degree relative with history of heart attack or stroke; * Current nicotine use; * Self-reported claustrophobia * Peanut allergy * all reported prescription medications will be reviewed and cleared by a study physician prior to a participant's enrollment; * participants will be given the opportunity to describe these conditions in the online screening survey. Reported conditions that are acute in nature and/or benign will be reviewed by a study physician and exclusions will be decided case-by-case. All chronic conditions will be exclusionary. For those where it is deemed that an exclusion does not apply, primary analyses will not be affected, but exploratory analyses will be conducted excluding these individuals

Inclusion Criteria

Exclusion Criteria

* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures, lifestyle considerations, and availability for the duration of the study
* 44-55 years old unmedicated perimenopausal women who have ≥ 2 skipped menstrual cycles, amenorrhea ≥ 60 days, corresponding to the late menopause transition (Stages of Reproductive Aging Workshop (STRAW stage -1).
* Anhedonia or psychosis symptoms that began during the period of menstrual irregularity.
* Clinician's Global Impression Scale-Severity score (CGI-S) \> 3 to confirm a clinically impaired sample.
* Anhedonia severity inclusion criteria and stratification: All participants will have Snaith-Hamilton Pleasure Scale (SHAPS) scores \> 20 consistent with the NIMH Fast-Fail Trial for Mood and Anxiety Disorders, corresponding to clinically impairing anhedonia.
* Psychosis severity inclusion criteria and stratification: Participants will be stratified according to scores on the psychotic subscale of the Brief Psychiatric Rating Scale (BPRS)
* Willingness to adhere to the estradiol regimen

* Pregnancy; allergies to any active or inactive ingredients in the Climara® patch or Prometrium®.
* BMI \< 18 or \> 35 kg/m\^2
* A history of chronic menstrual cycle irregularity, meaning \> 1 year without menses
* MR contraindications: Metal in the body, dental work other than fillings or gold, tattoos, metal injury, any other implant unless they are 100% plastic.
* PET contradictions: participation in \>1 research study in the past 12 months that included ionizing radiation exceeding 3 rem to the whole body (e.g., PET, CT). Standard of care imaging is not exclusionary.
* The use of psychotropics or hormonal preparations.
* History of psychiatric illness during the 2 years before the onset of perimenopause.
* History of chronic, recurrent mood or psychotic disorders (i.e., more than one non-reproductive-related mood episode prior to the perimenopausal index episode).
* A history of mood episodes requiring hospitalization.
* Current mania;
* Depressive episode(s) within 2 years of enrollment not associated with the transition to menopause;
* A history of suicide attempts within the last year or current active suicidal ideation with intent and plan.
* Neurological conditions (e.g., history of seizure or TBI)
* Brain stimulation treatment in the past six months.
* Endometriosis;
* First degree relative with premenopausal breast cancer or breast cancer presenting in both breasts or multiple family members (greater than three relatives) with postmenopausal breast cancer.
* Current medication use (i.e., current psychotropics, current anti-hypertensives, current statins, current 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;
* Last menstrual period 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;
* Abnormal finding in a provider breast exam and/or mammogram;
* Known carrier of BRCA1 or 2 mutation;
* Porphyria;
* Malignant melanoma;
* Hodgkin's disease;
* Recurrent migraine headaches that are preceded by aura;
* Gallbladder or pancreatic disease\*\*;
* Heart or kidney disease\*\*;
* Liver disease;
* cerebrovascular disease (stroke);
* First degree relative with history of heart attack or stroke;
* Current nicotine use;
* Self-reported claustrophobia
* Peanut allergy
* all reported prescription medications will be reviewed and cleared by a study physician prior to a participant's enrollment;
* participants will be given the opportunity to describe these conditions in the online screening survey. Reported conditions that are acute in nature and/or benign will be reviewed by a study physician and exclusions will be decided case-by-case. All chronic conditions will be exclusionary. For those where it is deemed that an exclusion does not apply, primary analyses will not be affected, but exploratory analyses will be conducted excluding these individuals

Contacts and Locations

Study Contact

Kathryn G Gibson, BS

CONTACT

919-966-5243

kathryn_gibson@med.unc.edu

Laura C Lundegard, BA

CONTACT

919-966-5243

laura_lundegard@med.unc.edu

Principal Investigator

Crystal E Schiller, PhD

PRINCIPAL_INVESTIGATOR

UNC School of Medicine - Department of Psychiatry

Gabriel Dichter, PhD

PRINCIPAL_INVESTIGATOR

UNC School of Medicine - CIDD

Study Locations (Sites)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514

United States

Collaborators and Investigators

Sponsor: University of North Carolina, Chapel Hill

Crystal E Schiller, PhD, PRINCIPAL_INVESTIGATOR, UNC School of Medicine - Department of Psychiatry
Gabriel Dichter, PhD, PRINCIPAL_INVESTIGATOR, UNC School of Medicine - CIDD

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-04-20

Study Completion Date2026-12-31

Study Record Updates

Study Start Date2022-04-20

Study Completion Date2026-12-31

Terms related to this study

Keywords Provided by Researchers

Reproductive Affective Disorder
Anhedonia
Perimenopause
Estrogen
Hormone Replacement Therapy
Mood Disorders
Estradiol Treatment
Sex Steroids
Psychosis Symptoms
Depressive Disorders
Estradiol
Hormones
Reward Activation
Reproductive Control Agents

Additional Relevant MeSH Terms

Depression
Psychosis
Anhedonia