Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 4INTERVENTIONAL

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

Q: What is the NCT05282277 clinical trial studying?

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). The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Q: Who can participate in NCT05282277?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

Q: How do I contact the trial site for NCT05282277?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Q: Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Q: Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

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

Examining the Effects of Estradiol on Neural and Molecular Response to Reward (NCT05282277) is a Phase 4 interventional studying Depression and Psychosis, sponsored by University of North Carolina, Chapel Hill. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

What Stage of Research Is This?

Phase 4 studies happen after a treatment has been approved by the FDA. They monitor long-term safety, real-world effectiveness, and any rare side effects that only emerge in larger populations over longer periods. Phase 4 results sometimes lead to label changes, additional warnings, or — rarely — withdrawal of approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 103 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Depression subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - Provision of signed and dated willing to sign a consent form 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 Who Should NOT Join This Trial: - 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion 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 Exclusion Criteria: * 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

Treatments Being Tested

DRUG

Transdermal Estradiol

Participants will be randomized to receive transdermal estradiol (100μg/day) patch for 3 weeks.

DRUG

Micronized Progesterone

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

DRUG

Matching Placebo Patch

Participants will be randomized to receive a transdermal estradiol-matching placebo patch for 3 weeks

DRUG

Raclopride C11

All Participants will receive two PET-MR scans using \[11C\]raclopride IV as the tracer. The first scan will occur at baseline and the second at post treatment after 3 weeks.

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT05282277), the sponsor (University of North Carolina, Chapel Hill), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT05282277 clinical trial studying?

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). The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT05282277?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT05282277?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT05282277. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT05282277. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.