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Sponsored by: |
National Institute of Mental Health (NIMH) |
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Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00030147 |
The purpose of this study is to evaluate the effectiveness of the drugs raloxifene and rimostil in treating perimenopause-related depression.
Perimenopause-related mood disorders cause significant distress to a large number of women; the demand for effective therapies to treat these mood disorders is considerable. Estradiol replacement therapy (ERT) has demonstrated efficacy in treating perimenopause-related depression. Unfortunately, there are long-term risks associated with ERT. Selective estrogen receptor modulators (SERMS), such as raloxifene, and phytoestrogens, such as rimostil, have estrogen-like properties and may offer a safer alternative to ERT. The effect of SERMS and phytoestrogens on mood and cognitive functioning need to be examined in women with perimenopause-related depression.
Participants in this study will undergo a medical history, physical examination, electrocardiogram (EKG), and blood and urine tests. They will then be randomly assigned to receive one of four treatments for 8 weeks: raloxifene pills plus a placebo (an inactive substance) skin patch, rimostil pills plus placebo skin patch, estradiol skin patch plus placebo pills, or placebo patch plus placebo pills. Participants will have clinic visits every 2 weeks. During the visits, blood will be drawn and participants will meet with staff members and complete symptom self-rating scales. A urine and blood sample will be collected at the beginning and end of the study. At the end of the study, participants who received placebo or whose study medication was ineffective will be offered treatment with standard antidepressant medications for 8 weeks. Non-menstruating women will receive progesterone for 10 days to induce menstrual bleeding and shedding of the inner layer of the uterus, which may have been stimulated by the study medications.
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Condition | Intervention | Phase |
---|---|---|
Perimenopausal Depression Depression |
Drug: Raloxefine (Evista) Drug: Rimostil Drug: Estradiol (Alora) |
Phase IV |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study |
Official Title: | The Efficacy of Selective Estrogen Receptor Modulators in Perimenopause-Related Depression |
Estimated Enrollment: | 88 |
Study Start Date: | February 2002 |
Arms | Assigned Interventions |
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1: Experimental
Dose of 60 mg per day for eight weeks
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Drug: Raloxefine (Evista)
N/A
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2: Experimental
Dose of 1000 mg twice a day for eight weeks
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Drug: Rimostil
N/A
|
3: Active Comparator
Dose of 100 micrograms a day by skin patch for eight weeks.
|
Drug: Estradiol (Alora)
N/A
|
Perimenopause-related mood disorders cause significant distress to a potentially large number of women. The demand for effective therapeutic alternatives to estrogen for treating these mood disorders is considerable, as is the need to define clinical or biologic markers that may predict successful response of mood disturbances to phytoestrogens or selective estrogen receptor modulators (SERMs). Further, the study of potential biological mechanisms underlying both perimenopause-related mood disorders and their response to treatment may offer the possibility of uncovering some etiopathogenic mechanisms involved in these and related mood disorders.
Results of protocol # 90-M-0077 demonstrated the therapeutic efficacy of estradiol therapy (ET) in perimenopausal depression, independent of its effects on vasomotor symptoms. Nevertheless, the long term risks of ET to endometrial and breast tissues continue to deter many women from its use. Recently, selective estrogen receptor modulators (SERMs) and phytoestrogens (plant-derived estrogen-like compounds) have become available and are reported to display both tissue-specific profiles of estrogen agonist and antagonist actions and differential affinities for the two forms of estrogen receptor. For many women, these novel compounds would represent a safer alternative to ET for the prevention of osteoporosis and the treatment of menopausal symptoms. However, the effects of SERMs and phytoestrogens on mood and cognitive function in perimenopausal women remain undetermined.
In this protocol we wish both to investigate the effects of SERMs and phytoestrogens on mood and cognition under placebo controlled conditions and to compare these effects with estradiol therapy. This protocol will address the following questions: 1) Do selective estrogen receptor modulators or phytoestrogens improve mood and cognition in perimenopausal depressed women? 2) Are the mood and cognitive effects of SERMs and phytoestrogens comparable to those of ET? and 3) Do selective estrogen receptor modulators and phytoestrogens improve measures of bone metabolism in perimenopausal depressed women?
Ages Eligible for Study: | 40 Years to 60 Years |
Genders Eligible for Study: | Female |
Accepts Healthy Volunteers: | Yes |
Subjects for this study will meet the following criteria:
EXCLUSION CRITERIA:
The following conditions will constitute contraindications to treatment and will preclude a subject's participation in this protocol:
1) Severe major depression with any of the following:
2) Current treatment with antidepressant medications. Our main concern is to exclude subjects taking medications that would treat or precipitate depression or adversely interact with reproductive hormones, phytoestrogens (e.g., anticoagulants), or SERMs. Thus, we wish to exclude only women receiving psychotropic medications, medications that have been reported to induce a change in mood or behavior, hormone replacement therapy, oral contraceptive agents, or medications that may have a potential adverse interaction with the compounds employed in this study.
3) History of psychiatric illness during the two years before the reported onset of the current episode of depression.
4) History of ischemic cardiac disease, pulmonary embolism, retinal thrombosis, or thrombophlebitis; any subject with risk factors for thrombo-embolic phenomena including cigarette smokers; varicose veins, patients with prolonged periods of immobilization (including prolonged travel), and active heart disease. The literature suggests that although both smoking and hormone replacement/oral contraceptives have associated risks of thromboembolic phenomena and cardiovascular events, these individual risks do not become significantly greater when combined until greater than 10 cigarettes a day are consumed. Thus we wish to exclude only subjects for this study who smoke greater than 10 cigarettes per day.
5) Renal disease, asthma.
6) Hepatic dysfunction.
7) Women with a history of carcinoma of the breast, or any women with a family history of the following: premenopausal breast cancer or bilateral breast cancer in a first degree relative; multiple family members (greater than three relatives) with postmenopausal breast cancer.
8) Women with a history of uterine cancer, endometriosis, ill-defined pelvic lesions, particularly undiagnosed ovarian enlargement, undiagnosed vaginal bleeding.
9) Patients with a known hypersensitivity to raloxifene, phytoestrogens (including Rimostil, isoflavones, genistein, daidzein, red clover extract and soy-related compounds), estradiol, Alora, medroxyprogesterone acetate, or the excipients (inactive compounds) contained within these medications including: Rimostil -tocopherols, cellulose, calcium hydrogen phosphate, magnesium stearate, silica-colloidal anhydrous; Provera - calcium stearate, corn starch, lactose, mineral oil, sorbic acid, sucrose, talc; Alora - sorbitan monooleate, acrylic adhesive; Evista - anhydrous lactose, carnauba wax, crospovidone, FD& C blue # 2 aluminum lake, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, modified pharmaceutical glaze, polyethylene glycol, polysorbate 80, povidone, and titanium dioxide.
10) Pregnant women.
11) Porphyria.
12) Diabetes mellitus.
13) Cholecystitis or pancreatitis.
14) History of cerebrovascular disease (stroke), epilepsy, hypertension, hypercalcemia.
15) Recurrent migraine headaches.
16) Malignant melanoma.
17) History of familial hyperlipoproteinemia.
Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
Contact: Peter J. Schmidt, M.D. | (301) 496-6120 | PeterSchmidt@mail.nih.gov |
United States, Maryland | |
National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
Bethesda, Maryland, United States, 20892 |
Responsible Party: | National Institutes of Health ( Peter J. Schmidt, M.D./National Institute of Mental Health ) |
Study ID Numbers: | 020120, 02-M-0120 |
Study First Received: | February 6, 2002 |
Last Updated: | January 27, 2009 |
ClinicalTrials.gov Identifier: | NCT00030147 |
Health Authority: | United States: Federal Government |
Gonadal Steroids Estrogen Receptor Mood Disorders Perimenopause Estradiol |
Depression Estrogen Response Element Depression Perimenopausal Perimenopausal Depression |
Raloxifene Depression Mental Disorders Estradiol 3-benzoate Estradiol valerate Mood Disorders |
Estradiol 17 beta-cypionate Polyestradiol phosphate Depressive Disorder Estradiol Behavioral Symptoms |
Estrogens Physiological Effects of Drugs Hormones, Hormone Substitutes, and Hormone Antagonists Hormones Pharmacologic Actions |