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Effects of a Tissue Selective Estrogen Complex (TSEC) on Depression and the Neural Reward System in the Perimenopause" (Duavee)

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ClinicalTrials.gov Identifier: NCT03740009
Recruitment Status : Recruiting
First Posted : November 14, 2018
Last Update Posted : January 9, 2019
Sponsor:
Collaborator:
Foundation of Hope, North Carolina
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Brief Summary:
Using neuroimaging, the investigator will study the effects of estrogen on mood and brain function in perimenopausal women with depression.

Condition or disease Intervention/treatment Phase
Perimenopausal Disorder Depression Drug: Bazedoxifene/Conjugated Estrogen Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Effects of a Tissue Selective Estrogen Complex (TESC) on Depression and the Neural Reward System in the Perimenopause
Actual Study Start Date : January 2, 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Perimenopausal women, depressed
Participants will take Bazedoxifene/Conjugated Estrogen orally for 3 weeks
Drug: Bazedoxifene/Conjugated Estrogen
20 mg bazedoxifene/0.45mg conjugated estrogens tablets
Other Name: Duavee




Primary Outcome Measures :
  1. Change in frontostriatal reactivity to reward during MID fMRI task [ Time Frame: Baseline and at week 3 ]
    The primary outcome measure is functional magnetic resonance imaging (fMRI) data collected during a Monetary Incentive Delay (MID) Task. All participants will complete the fMRI Monetary Incentive Delay (MID) task on each study day. During the task, participants need to select the correct response during "win" and "lose" conditions by pressing a button on a button box in the MRI. Participant's blood-oxygen-level dependent (BOLD) activation response (A measurement of oxygen level that is released to neurons since areas of the brain that are thought to be more "active" or involved in certain tasks require more oxygen to perform the tasks.) is measured while they performed the task in MRI scanner.


Secondary Outcome Measures :
  1. Change in neural connectivity required during resting state fMRI [ Time Frame: Baseline and at week 3 ]
    Resting state scans will be conducted at the beginning and end of each fMRI session.



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Ages Eligible for Study:   44 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Men will not be included in this study, given the stated purpose of studying hormone therapy in perimenopausal women.
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • The investigators will employ the Stages of Reproductive Aging Workshop (STRAW) criteria to confirm perimenopausal status. The stages are primarily based on the characteristics of the menstrual cycle and secondarily on follicle stimulating hormone (FSH) levels. The anchor for the staging system is the last menstrual period (LMP). The investigators will enroll women who have > 2 skipped cycles with an interval of amenorrhea > 60 days and FSH values > 14, consistent with the late menopause transition (stage-1)*. Women who have taken oral contraceptives continuously for relief of perimenopausal symptoms will be exempt from our LMP criteria, and their perimenopausal status will be determined by FSH alone. Because extremes of body weight (BMI < 18 or > 35 kg/m2) or a history of chronic menstrual cycle irregularity can contribute to inaccurate reproductive staging, these will serve as additional exclusion criteria.

Current diagnosis of MDD with an onset associated with menstrual cycle irregularity. Present or past mania, psychosis, suicide attempts, and alcohol or drug dependence, and current substance abuse, as determined by the Structure Clinical Interview for The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) for Axis I Disorders (SCID) are exclusionary.

* Per the STRAW criteria, FSH values are highly variable in the late menopausal transition (stage -1), and clinicians should "carefully evaluate the appropriate FSH value, depending on the assay they use" (Harlow et al, 2012). For nearly two years following the LMP, FSH values can fluctuate between levels characteristic of the early reproductive years and levels characteristic of menopause (Hale et al, 2014). McLendon Labs at the University of North Carolina at Chapel Hill (UNC) uses an FSH assay that defines levels consistently above ? 21.5 IU/mL as post-menopausal (McLendon Labs, 2016). As FSH values do not stabilize at consistently high levels until post-menopause, the investigators are setting our minimum required FSH value at > 14 IU/mL to carefully select for women in the perimenopause transition.

Exclusion Criteria:

  • Patients will not be permitted to enter this protocol if they have any of the following:

    1. current medication use (i.e., psychotropics, anti-hypertensives, statins, hormonal preparations, or frequent use of anti-inflammatory agents (> 10 times/month)). Women will be allowed to enroll who take medications without known mood effects (e.g. stable thyroid hormone replacement and occasional (< 5 times/month) use of Ambien);

      • all reported prescription medications will be reviewed and cleared by a study physician prior to a participant's enrollment;
    2. pregnant, breastfeeding or trying to conceive;
    3. LMP more than 12 months prior to enrollment;

      • women who have recently taken oral contraceptives continuously for relief of perimenopausal symptoms will be exempt from the final menstrual period (FMP) criteria, and instead, the presence of menstrual irregularity prior to the use of oral contraceptives and elevated FSH will be used to determine their perimenopausal status;
    4. history of undiagnosed vaginal bleeding;
    5. undiagnosed enlargement of the ovaries;
    6. polycystic ovary syndrome;
    7. history of breast or ovarian cancer;
    8. first degree relative with ovarian cancer;
    9. first degree relative with premenopausal onset or bilateral breast cancer;
    10. 2+ first degree relatives with breast cancer (regardless of onset);
    11. 3+ relatives with postmenopausal breast cancer;
    12. abnormal finding in a provider breast exam and/or mammogram;

      • participants will be given the opportunity to describe these conditions in the online screening survey. Reported conditions that were acute in nature and have resolved completely (as indicated by the medical record or follow-up testing) and/or benign will be reviewed by a study physician prior to enrollment. All chronic conditions will be exclusionary.
    13. known carrier of BRCA1 or 2 mutation;
    14. endometriosis;
    15. blood clots in the legs or lungs;
    16. porphyria;
    17. diabetes mellitus;
    18. malignant melanoma;
    19. Hodgkin's disease;
    20. recurrent migraine headaches that are preceded by aura;
    21. gallbladder or pancreatic disease;

      • participants will be given the opportunity to describe these conditions in the online screening survey. Reported conditions that were acute in nature and have resolved completely (as indicated by the medical record or follow-up testing) and/or benign will be reviewed by a study physician prior to enrollment. All chronic conditions will be exclusionary.
    22. heart or kidney disease;

      • participants will be given the opportunity to describe these conditions in the online screening survey. Reported conditions that were acute in nature and have resolved completely (as indicated by the medical record or follow-up testing) and/or benign will be reviewed by a study physician prior to enrollment. All chronic conditions will be exclusionary.
    23. liver disease;
    24. cerebrovascular disease (stroke);
    25. current cigarette smoking;
    26. current suicidal ideation, mania, psychosis, or alcohol/drug abuse/dependence;
    27. past suicide attempts, mania, alcohol/drug dependence, or psychotic episodes;
    28. chronic depression (i.e., episode(s) lasting 3+ years);
    29. depressive episode(s) within 2 years of enrollment;
    30. self-reported claustrophobia;
    31. peanut allergy;
    32. HIV/AIDS

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): NCT03740009


Contacts
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Contact: Laura C Lundegard, BA (919)966-5243 laura_lundegard@med.unc.edu
Contact: Erin C Richardson, NP (919)966-0858 erin_richardson@med.unc.edu

Locations
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United States, North Carolina
University of North Carolina at Chapel Hill School of Medicine Recruiting
Chapel Hill, North Carolina, United States, 27514
Contact: Laura C Lundegard, BA    919-966-5243    laura_lundegard@med.unc.edu   
Contact: Erin C Richardson, PMHNP-BC    (919)966-0858      
Principal Investigator: Crystal E Schiller, PhD         
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Foundation of Hope, North Carolina
Investigators
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Principal Investigator: Crystal E Schiller, PhD UNC Dept of Psychiatry

Publications:
Schiller, C. The hormone withdrawal hypothesis of postpartum depression: a translational approach. Theses Diss. (2011).
U.S. Census Bureau. Age and Sex Composition: 2010. (2011).
First, M. B., Spitzer, R. L., Gibbon, M. & Williams, J. B. W. Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition. (SCID-I/NP). (Biometrics Research, New York State Psychiatric Institute, 2002).
McLendon Labs. (2016). Follicle Stimulating Hormone (FSH). Retrieved from: http://www.uncmedicalcenter.org/mclendon-clinical-laboratories/available-tests/follicle-stimulating-hormone-fsh/

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Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT03740009     History of Changes
Other Study ID Numbers: 18-2129
First Posted: November 14, 2018    Key Record Dates
Last Update Posted: January 9, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by University of North Carolina, Chapel Hill:
Hormone Replacement Therapy
Estrogen
Depression
Mood Disorders
Estrogen Replacement Therapy
Depressive Disorder
Mental Disorders
Hormones
Physiological effects of drugs
Reproductive Control Agents
Tissue Selective Estrogen Complex

Additional relevant MeSH terms:
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Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Bazedoxifene
Estrogens, Conjugated (USP)
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Bone Density Conservation Agents