Protocol Details
The Effects of an ER Beta Agonist (Lilly Compound LY500307) on Estradiol-withdrawal-induced Mood Symptoms in Women with Past Perimenopausal Depression
This study is NOT currently recruiting participants.
Summary
Number |
18-M-0144 |
Sponsoring Institute |
National Institute of Mental Health (NIMH) |
Recruitment Detail |
Type: Completed Study; data analyses ongoing
Gender: Female
Min Age: 45 Years
Max Age: 65 Years |
Referral Letter Required |
No |
Population Exclusion(s) |
Male;
Children |
Keywords |
Perimenopause-related depression |
Recruitment Keyword(s) |
None |
Condition(s) |
Perimenopause-Related Depression |
Investigational Drug(s) |
erteberel
|
Investigational Device(s) |
None |
Intervention(s) |
Drug: Estradiol
Other: Placebo
Drug: ER Beta Agonist
Drug: Provera
|
Supporting Site |
National Institute of Mental Health |
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.
Eligibility
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INCLUSION CRITERIA:
1. 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.
2. Age 45 to 65
3. 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).
4. Subjects must have consent capacity
EXCLUSION CRITERIA:
The following conditions will constitute contraindications to participate in this protocol:
1. Any current Axis 1 psychiatric illness or any clinically significant sleep disorder;
2. Women with histories of hormone replacement therapy-induced dysphoria due to either the estrogen or the progesterone components of their hormone replacement;
3. Past history of major depression with suicidal ideation;
4.History of ischemic cardiac disease, pulmonary embolism, or thrombophlebitis;
5. Renal disease; hepatic dysfunction; history of cholecystitis; hypertension;
6. Women with a history of carcinoma of the breast or any undiagnosed breast nodule/mass;
7. Women with a history of uterine cancer, ill-defined pelvic lesions, particularly undiagnosed ovarian enlargement, undiagnosed vaginal bleeding;
8. Pregnant women; sexually active women will be required to employ barrier contraceptive methods;
9. Cerebrovascular disease (stroke);
10. Recurrent migraine headaches;
11. Women who have had a hysterectomy before one year after their last menstrual period.
National Institute of Mental Health (NIMH) employees/staff and their immediate family members will be excluded from the study per NIMH policy.
Citations:
Cohen LS, Soares CN, Vitonis AF, Otto MW, Harlow BL. Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles. Arch Gen Psychiatry. 2006 Apr;63(4):385-90.
Freeman EW, Sammel MD, Lin H, Nelson DB. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry. 2006 Apr;63(4):375-82.
Freeman EW. Associations of depression with the transition to menopause. Menopause. 2010 Jul;17(4):823-7.
Contacts:
Clinical Trials Number:
NCT03689543