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Effects of an ER Beta Agonist (Lilly Compound LY500307) on Estradiol-Withdrawal-Induced Mood Symptoms in Women With Past Perimenopausal Depression

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ClinicalTrials.gov Identifier: NCT03689543
Recruitment Status : Recruiting
First Posted : September 28, 2018
Last Update Posted : May 21, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Perimenopause Depression Mood Disorders Drug: ER beta agonist Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: The Effects of an Estrogen Receptor (ER) Beta Agonist (Lilly Compound LY500307) on Estradiol-withdrawal-induced Mood Symptoms in Women With Past Perimenopausal Depression.
Estimated Study Start Date : May 24, 2019
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Estradiol

Arm Intervention/treatment
Experimental: 1
all women receive open label (OL) estradiol therapy (ET) at a dose of 100 micrograms per day bytransdermal skin patch
Drug: ER beta agonist
Lilly Compound LY500307

Experimental: 2
all women receive three weeks of double blind (DB) medication (i.e., LY500307 [at a daily dose of either 25 mg or 75 mg] or placebo)
Drug: ER beta agonist
Lilly Compound LY500307




Primary Outcome Measures :
  1. Epidemiologic Studies-Depression Scale (CES-D) [ Time Frame: Ongoing ]
  2. bserver ratings - the 17-item Hamilton Rating Scale of Depression(HRSD) [ Time Frame: Ongoing ]

Secondary Outcome Measures :
  1. Endometrial thickness as measured by vaginal ultrasound [ Time Frame: Ongoing ]
  2. Plasma LH, FSH, prolactin, and lipid levels [ Time Frame: Ongoing ]
  3. Visual analogue scale (VAS) [ Time Frame: Ongoing ]
  4. Beck Depression Inventory (BDI) [ Time Frame: Ongoing ]
  5. 14 item six point likert-type scale [ Time Frame: Ongoing ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   45 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria
  • 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 have previously completed the screening protocol # 88-M-0131 during which psychiatric, medical, and reproductive evaluations will be performed and they will have been confirmed to be 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03689543


Contacts
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Contact: Peter J Schmidt, M.D. (301) 496-6120 peterschmidt@mail.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Peter J Schmidt, M.D. National Institute of Mental Health (NIMH)

Additional Information:
Publications:
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Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT03689543     History of Changes
Other Study ID Numbers: 180144
18-M-0144
First Posted: September 28, 2018    Key Record Dates
Last Update Posted: May 21, 2019
Last Verified: April 30, 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) ):
Estrogen Receptor
Menopause
Estrogen

Additional relevant MeSH terms:
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Depression
Depressive Disorder
Mood Disorders
Behavioral Symptoms
Mental Disorders
Estradiol
Polyestradiol phosphate
Estrogens
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female