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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 | Eligibility | Citations | Contacts

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: ER beta agonist
Other: Placebo

Supporting Site

National Institute of Mental Health

Background:

Some women who had depression in the perimenopause may have mood symptoms again if they stop estrogen therapy. Estrogen acts in the brain and other tissues by binding to at least three types of estrogen receptors. One of these receptors, estrogen receptor beta may affect anxiety and depression. The drug LY500307 acts only on this receptor. In this study, researchers will initially give you estrogen and then suddenly stop estrogen after three weeks. Then they will study how LY500307 affects mood symptoms.

Objectives:

To study how withdrawing estradiol affects mood. To test the safety and side effects of LY500307.

Eligibility:

Healthy women ages 45-65 who had depression related to perimenopause in recent 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 uturus.

-Participants will have a final visit 4 weeks after stopping the study drug. They will answer questions about mood and side effects.

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Eligibility

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 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.

NIMH employees/staff and their immediate family members will be excluded from the study per NIMH policy.


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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.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Peter J. Schmidt, M.D.
National Institute of Mental Health (NIMH)
NIHBC 10 - CLINICAL CENTER BG RM 4C404
10 CENTER DR
BETHESDA MD 20892
(301) 496-6120
peterschmidt@mail.nih.gov

Annie K. Shellswick
National Institute of Mental Health (NIMH)
National Institutes of Health
Building 10
Room 2-5330
10 Center Drive
Bethesda, Maryland 20892
(301) 402-9207
annieshellswick@mail.nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1
ccopr@nih.gov

Clinical Trials Number:

NCT03689543

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