Estrogen Receptor Beta and Mood (NCT03689543) | Clinical Trial Compass
CompletedPhase 2
Estrogen Receptor Beta and Mood
United States74 participantsStarted 2019-05-23
Plain-language summary
Background:
Our previous studies have found that women who had depression during the perimenopause may have mood symptoms again if they stop estrogen therapy. Estrogen acts in the brain and other tissues by binding to estrogen receptors. There are two main types of estrogen receptors. They are estrogen receptor alpha and beta. Several studies have shown that estrogen receptor beta may play an important role in anxiety- and depressive-like behaviors in animals.
Objectives:
To examine a possible mechanism mediating the effects of estradiol-withdrawal on mood symptoms in asymptomatic postmenopausal women with a past perimenopausal depression. To evaluate the efficacy and safety of a selective estrogen receptor (ER) beta agonist (Lilly Compound LY500307) to prevent estradiol withdrawal-induced mood symptoms.
Eligibility:
Healthy, non-depressed postmenopausal women, ages 45 to 65, with a well-documented past perimenopause-related depression (within 12 years) and whose mood systems got better with estradiol
Design:
Participants will be screened with:
Medical history
Physical exam
Blood tests
Psychiatric interview
Gynecological exam
* Participants able to get pregnant must use effective barrier birth control throughout the study.
* During the first 3 weeks, participants will wear an estrogen patch. It is 1x2 inches and will be replaced every 3 days.
* For the next 3 weeks, participants will take 3 study capsules every morning. They will not know if they get the study drug or placebo.
* Some participants will also take a progesterone-like drug for 1 week at the end of the medication phase of the study.
* Participants will have 9 one-hour study visits. They will have blood samples and vital signs taken. They will answer questions about mood and behavior symptoms.
* Participants will keep a daily log of these symptoms.
* Participants will have 2 transvaginal ultrasounds. A probe is temporarily placed 2-3 inches into the vaginal canal and sound waves are used to create pictures of the lining of the uterus.
* Participants will have a final visit 4 weeks after stopping the study drug. They will answer questions about mood and side effects.
Who can participate
Age range45 Years – 65 Years
SexFEMALE
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Inclusion criteria
✓. Women with a past perimenopause-related depression (within 12 years). The diagnosis of perimenopause-related depression will be based on a history of a past depressive episode (major or minor depression confirmed by Structured Clinical Interview for Diagnostic and Statistical Manual (DSM)-V (SCID)) at midlife in association with menstrual cycle irregularity (and possibly hot flushes and/or vaginal dryness) and in whom menopausal hormone therapy was reported to improve their depression at any time within the prior twelve years. All women participating in this protocol will be screened with psychiatric, medical, and reproductive evaluations to confirm they are in good medical health.
✓. Age 45 to 65
✓. Medication free (including no mood stabilizers, no sleep medication) except for the following: women on menopausal hormone therapy who will discontinue these medications at the start of this study and have their hormone therapy replaced with estradiol 100mcg per day (as described below), women who are on stable doses of thyroid replacement for at least six months prior to study enrollment, or women who occasionally take non-steroidal anti-inflammatory drugs \[NSAIDs\] or allergy medications (although we will ask women to minimize the use of these medications during the study).
✓. Subjects must have consent capacity
Exclusion criteria
What they're measuring
1
Center for Epidemiologic Studies-Depression (CES-D) Scale Mean Total Score
Timeframe: Baseline, then weekly through end of week six
2
Hamilton Rating Scale of Depression (HRSD) Mean Total Score
Timeframe: Baseline, then weekly through end of week six
. Any current Axis 1 psychiatric illness or any clinically significant sleep disorder;
✕. Women with histories of hormone replacement therapy-induced dysphoria due to either the estrogen or the progesterone components of their hormone replacement;
✕. Past history of major depression with suicidal ideation;
✕. History of ischemic cardiac disease, pulmonary embolism, or thrombophlebitis;
✕. Renal disease; hepatic dysfunction; history of cholecystitis; hypertension;
✕. Women with a history of carcinoma of the breast or any undiagnosed breast nodule/mass;
✕. Women with a history of uterine cancer, ill-defined pelvic lesions, particularly undiagnosed ovarian enlargement, undiagnosed vaginal bleeding;
✕. Pregnant women; sexually active women will be required to employ barrier contraceptive methods;