Examining the Effects of Estradiol on Neural and Molecular Response to Reward
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexFemale
Age45-55
SponsorUniversity of North Carolina, Chapel Hill
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
Pregnancy; allergies to any active or inactive ingredients in the Climara® patch or Prometrium®.
BMI < 18 or > 35 kg/m²
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Transdermal Estradiol
DrugParticipants will be randomized to receive transdermal estradiol (100μg/day) patch for 3 weeks.
Micronized Progesterone
DrugParticipants will receive an additional week of micronized progesterone (200 mg/day) at the end of the study to precipitate menstruation.
Matching Placebo Patch
DrugParticipants will be randomized to receive a transdermal estradiol-matching placebo patch for 3 weeks
Raclopride C11
DrugAll 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.
Treatment groups
103 Participants
are divided into 8 treatment groups8
Treatment groupsSee each treatment group below.
Group A: Perimenopausal women with mild-to-moderate anhedonia + absent-to-mild psychosis, active groupExperimental treatment 3 interventions
Group B: Perimenopausal women with mild-to-moderate anhedonia + absent-to-mild psychosis, placebo groupExperimental treatment 2 interventions
Group C: Perimenopausal women with mild-to-moderate anhedonia + moderate psychosis, active groupExperimental treatment 3 interventions
Group D: Perimenopausal women with mild-to-moderate anhedonia + moderate psychosis, placebo groupExperimental treatment 2 interventions
Group E: Perimenopausal women with high anhedonia + absent-to-mild psychosis, active groupExperimental treatment 3 interventions
Group F: Perimenopausal women with high anhedonia + absent-to-mild psychosis, placebo groupExperimental treatment 2 interventions
Group G: Perimenopausal women with high anhedonia + moderate psychosis, active groupExperimental treatment 3 interventions
Group H: Perimenopausal women with high anhedonia + moderate psychosis, placebo groupExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Changes in Striatal Activation Between Groups during the MID task
Characterize reward-related striatal activation measured by fMRI using the Monetary Incentive Delay (MID) task to elicit blood-oxygen-level dependent (BOLD) responses. 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) response to win trials versus non-win trials. Reactivity is then compared between the two groups.
Time frame
Baseline (week 3) to Endpoint (week 7)Secondary outcomes
1
Changes in PO Psychosis Symptoms following Estradiol Administration Using the BPRS
Determine the effects of estradiol (vs. placebo) on PO psychosis symptoms using the Brief Psychiatric Rating Scale (BPRS).The BPRS is an 18-item clinician rated psychosis measure that examines the severity of psychotic symptoms. Individuals with psychotic major depression typically have BPRS positive symptom subscale scores 7-11, and a score of 6 best differentiates psychotic MDD from nonpsychotic MDD.
Time frame
Baseline (week 3) to Endpoint (week 7)2
Changes in PO Anhedonia Following Estradiol Administration Using the SHAPS
Determine the effects of estradiol (vs. placebo) on PO anhedonia symptoms using the Snaith-Hamilton Pleasure Scale (SHAPS). The SHAPS is a 14-item self-rated anhedonia scale. Items are comprised of statements that participants rate as "strongly disagree" (1), "disagree" (2), "agree" (3), or "strongly agree" (4). The lowest possible score is 14, the highest possible score is 56 (greatest anhedonia)
Time frame
Baseline (week 3) to Endpoint (week 7)3
Change in striatal phasic DA release and background DA tone to rewards measured by [11C]raclopride PET using the Monetary Incentive Delay (MID) task.
Binding potential changes due to DA release and competition will be determined using a dynamic occupancy model. We will use baseline nondisplaceable binding potential (BPND) and change in BPND following task onset (ΔBPND%) to determine differences between groups in terms of the baseline (tonic) state and the activation (phasic) state.
Time frame
Baseline (week 3) to Endpoint (week 7)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
University of North Carolina, Chapel Hill
Lead sponsor
National Institute of Mental Health (NIMH)
Collaborator
Source ClinicalTrials.gov