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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: | NCT00082043 |
This study will explore the effects of dutasteride on mood and the stress response across the menstrual cycle. Dutasteride blocks production of neurosteroids-hormones that help regulate the stress response systems. These systems may be disturbed in women with menstrually related mood disorders (MRMD). The effects of the drug will be compared in women with and without MRMD to determine how neurosteroids regulate mood and the stress response across the menstrual cycle. Dutasteride is approved by the Food and Drug Administration to treat benign prostatic hyperplasia (excess growth of the prostate gland) in men.
Menstruating women 30 to 45 years of age with and without MRMD may be eligible for this study. Candidates are screened with a medical and psychiatric history, physical examination, screening for symptoms of depression, and routine blood and urine tests. Participants are required to use barrier contraception (condoms or diaphragm) during the 3-month study and 6-month follow-up.
Participants undergo the following tests and procedures:
Condition | Intervention | Phase |
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Premenstrual Syndrome PMS Healthy Depression |
Drug: Dutasteride Drug: Placebo oral capsule |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Crossover Assignment, Efficacy Study |
Official Title: | The Effects of Dutasteride on Mood, HPA Axis, and Serum Allopregnanolone Levels in Women With Menstrual-Related Mood Disorders and Controls |
Estimated Enrollment: | 36 |
Study Start Date: | March 2004 |
Arms | Assigned Interventions |
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1: Experimental
Dutasteride 0.5 mg by mouth daily for one month
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Drug: Dutasteride
N/A
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2: Placebo Comparator
Placebo oral capsule for two months
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Drug: Placebo oral capsule
N/A
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Studies of premenstrual syndrome (PMS) to date have demonstrated that the syndrome represents an abnormal response to normal physiological events. Specifically patients with PMS experience a dysphoric mood state in response to normal luteal phase levels of progesterone and additionally fail to demonstrate the augmentation of the hypothalamic-pituitary-adrenal (HPA) axis normally seen in the luteal phase. A parsimonious explanation for the dysregulation of both mood and HPA axis function in PMS is that both are mediated by abnormal levels of or response to the progesterone neurosteriod metabolite, allopregnanolone. Both exposure to and withdrawal from allopregnanolone have been shown to precipitate adverse mood states in animal studies, presumably consequent to induced conformational changes in the GABA(A) receptor (increased alpha-4 subunit) that impair GABA receptor function. This impairment of GABA receptor function may also be associated with loss of restraint of HPA axis activity and hence may underlie the luteal phase increases in HPA activity in normal women. In this protocol, we propose to block conversion of progesterone to allopregnanolone in women with menstrual-related mood disorder (MRMD; equivalent in most reports to a severe form of PMS called premenstrual dysphoric disorder (PMDD)) and in normal (control) women. We will block progesterone metabolism (and hence exposure to allopregnanolone) with a newly approved 5 alpha-reductase inhibitor, dutasteride. We hypothesize the following: 1) Elimination of exposure to allopregnanolone in women with MRMD will eliminate dysphoric mood in the luteal phase; 2) Elimination of exposure of normal control women to allopregnanolone will eliminate the luteal phase enhancement of stimulated stress axis activity response.
These hypotheses, if confirmed, will increase the precision with which we can dissect the pathophysiological mechanisms involved in MRMD and in menstrual-related stress physiology.
In this protocol, our study objectives are as follows: Primary Objectives: 1) Determine whether suppression of neurosteroid synthesis will diminish mood symptoms in women with MRMD. 2) Determine if suppression of neurosteroid synthesis will eliminate luteal phase-related increases in stimulated HPA axis activity in control women. Secondary Objectives: 1) Determine whether differences in response to allopregnanolone account for the divergent effects of menstrual cycle phase on HPA axis activity in patients with MRMD and controls. 2) Determine if the Dex-CRH test, like the graded stressor treadmill test, can reveal the effects of menstrual cycle phase on HPA axis function.
Ages Eligible for Study: | 30 Years to 45 Years |
Genders Eligible for Study: | Female |
Accepts Healthy Volunteers: | Yes |
Healthy controls and women who meet the criteria for MRMD.
The criteria for MRMD, from Protocol 81-M-126, "The Phenomenology and Biophysiology of Menstrually Regulated Mood and Behavior Disorders," briefly are as follows:
Healthy controls will have no symptoms of MRMD (confirmed prospectively), be between the ages of 30 and 45, and be in good physical health.
In addition all subjects will have a normal clinical breast exam prior to study entry.
EXCLUSION CRITERIA:
Subjects will be excluded from the study for the following reasons:
In addition to the above, due to the long half life of dutasteride and its teratogenic effects on male fetuses, only women who have already decided to discontinue child-bearing and are willing to continue barrier contraception for 6 months after the study will be included in the protocol.
Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
Contact: TTY | 1-866-411-1010 |
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: | 040139, 04-M-0139 |
Study First Received: | April 28, 2004 |
Last Updated: | September 15, 2008 |
ClinicalTrials.gov Identifier: | NCT00082043 |
Health Authority: | United States: Federal Government |
Neurosteroids 5 Alpha-Reductase Inhibitor Depression Menstrual Cycle Gonadal Steroids |
Menstrual Cycle Depression Menstrual Cycle Related Mood Disorder MRMD Healthy Volunteer |
Dutasteride Depression Menstruation Disturbances Mental Disorders Mood Disorders |
Healthy Depressive Disorder Premenstrual Syndrome Behavioral Symptoms |
Disease Pathologic Processes Molecular Mechanisms of Pharmacological Action |
Syndrome Enzyme Inhibitors Pharmacologic Actions |