Premenstrual SyndromePhase 1NCT00082043
Dutasteride to Treat Women With Menstrually Related Mood Disorders
A Phase 1 study testing Dutasteride in people with Premenstrual Syndrome and PMS, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 30 to 50 years, women only
- Conditions the study is for
- Premenstrual Syndrome, PMS, Healthy
- What is being tested?
- Dutasteride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Mar 2004to 6 Mar 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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:
- History within the last two years of at least six months with menstrually-related mood or behavioral disturbances of a severity sufficient to cause at least moderate subjective distress;
- Symptoms should have a sudden onset and offset, with symptoms most severe during the week prior to menstruation and tending to disappear abruptly on or about the first day menstruation;
- Age 30-50 years;
- In good physical health;
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- To qualify for study inclusion, women with MRMD will have prospectively demonstrated in at least two of three menstrual cycles a 30% worsening of mean negative mood symptoms in the premenstrual period compared to the week following menses, corrected for the range of the scales employed.
- Healthy controls will have no symptoms of MRMD (confirmed prospectively), be between the ages of 30 and 50, and be in good physical health.
- In addition all subjects will have a normal clinical breast exam prior to study entry.
Who cannot join
- Subjects will be excluded from the study for the following reasons:
- Pregnancy or any intent to become pregnant;
- Medical illness, in particular diabetes, cardiac or renal disease;
- Use of psychotropic or hormonal medications within three months prior to the study;
- Current prescription medication use;
- History of or current alcohol or drug abuse or dependence;
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- A history of (within the past two years) or current psychiatric disorder determined by administration of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID);
- Male gender;
- Age less than 30 years; and
- Women with a history of carcinoma of the breast, or 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 a history of postmenopausal breast cancer.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: The Effects of Dutasteride on Mood, HPA Axis, and Serum Allopregnanolone Levels in Women With Menstrual-Related Mood Disorders and Controls
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.
Read more
Participants undergo the following tests and procedures:
- Dutasteride or placebo treatment: Participants receive 1 month of dutasteride and 2 months of placebo. Neither the participants nor the investigators know when the subject is taking the active medication or the placebo.
- Biweekly follow-up visits: Every 2 weeks during the 3-month treatment period, patients come to the NIH Clinical Center to have blood drawn and to complete mood symptoms ratings.
- Monthly follow-up visits: Participants return to the Clinical Center once a month for 6 months after the end of the treatment period to monitor hormone levels and pregnancy status.
Read the detailed description
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.
- Conditions
- Premenstrual Syndrome, PMS, Healthy, Depression
- Being tested
- Dutasteride, Placebo oral capsule
- Keywords
- Neurosteroids, 5 Alpha-Reductase Inhibitor, Depression, Menstrual Cycle, Gonadal Steroids, Menstrual Cycle Related Mood Disorder, MRMD, Healthy Volunteer
- Medical subject headings
- Premenstrual Syndrome, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DutasterideDrug
Placebo oral capsuleDrug
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Dutasteride 2.5 mg by mouth daily for one month Receives: Drug: Dutasteride |
| 2 | Placebo comparator | Placebo oral capsule for two months Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rating Scale for Premenstrual Tension (PMTS); Daily symptom rating form (DRF); Visual Analogue Symptom (VAS) self-rating form.
Measured: Every 2 weeks for the PMTS; daily for the others.
Secondary outcomes (1)
Neuroendocrine response to DEX/crh test; Beck Depression Inventory (BDI)
Measured: DEX/crf 2x second mth of tx, 1x during luteal ph & 1x during follicular ph.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2004 (estimated)
- Study start31 Mar 2004
- Primary completion6 Mar 2014
- Study completion6 Mar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Premenstrual SyndromeStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Pedro E Martinez, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00082043
- Sponsor's protocol ID
- 040139
- Other IDs
- 04-M-0139
- Status last verified
- 5 Feb 2016
- First submitted
- 28 Apr 2004
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Halbreich U, Borenstein J, Pearlstein T, Kahn LS. The prevalence, impairment, impact, and burden of premenstrual dysphoric disorder (PMS/PMDD). Psychoneuroendocrinology. 2003 Aug;28 Suppl 3:1-23. doi: 10.1016/s0306-4530(03)00098-2.
PubMed 12892987Wittchen H -U, Becker E, Lieb R, Krause P. Prevalence, incidence and stability of premenstrual dysphoric disorder in the community. Psychol Med. 2002 Jan;32(1):119-32. doi: 10.1017/s0033291701004925.
PubMed 11883723Rubinow DR, Roy-Byrne P. Premenstrual syndromes: overview from a methodologic perspective. Am J Psychiatry. 1984 Feb;141(2):163-72. doi: 10.1176/ajp.141.2.163.
PubMed 6362441
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Dutasteride on Mood, HPA Axis, and Serum Allopregnanolone Levels in Women With Menstrual-Related Mood Disorders and Controls
- ClinicalTrials.gov ID
- NCT00082043
- Acronym / sponsor ID
- 040139
- Conditions
- Premenstrual Syndrome, PMS, Healthy, Depression
- Keywords
- Neurosteroids, 5 Alpha-Reductase Inhibitor, Depression, Menstrual Cycle, Gonadal Steroids, Menstrual Cycle Related Mood Disorder, MRMD, Healthy Volunteer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 31 Mar 2004
- Primary completion
- 6 Mar 2014 (actual)
- Study completion
- 6 Mar 2014 (actual)
- First posted
- 28 Apr 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Dutasteride or placebo treatment: Participants receive 1 month of dutasteride and 2 months of placebo. Neither the participants nor the investigators know when the subject is taking the active medication or the placebo.
- Biweekly follow-up visits: Every 2 weeks during the 3-month treatment period, patients come to the NIH Clinical Center to have blood drawn and to complete mood symptoms ratings.
- Monthly follow-up visits: Participants return to the Clinical Center once a month for 6 months after the end of the treatment period to monitor hormone levels and pregnancy status.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: DutasterideDutasteride 2.5 mg by mouth daily for one month |
| 2 | Placebo comparator | Drug: Placebo oral capsulePlacebo oral capsule for two months |
Who may qualify
- Ages
- 30 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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:
- History within the last two years of at least six months with menstrually-related mood or behavioral disturbances of a severity sufficient to cause at least moderate subjective distress;
- Symptoms should have a sudden onset and offset, with symptoms most severe during the week prior to menstruation and tending to disappear abruptly on or about the first day menstruation;
- Age 30-50 years;
Key exclusion criteria (11 listed)
- Pregnancy or any intent to become pregnant;
- Medical illness, in particular diabetes, cardiac or renal disease;
- Use of psychotropic or hormonal medications within three months prior to the study;
- Current prescription medication use;
- History of or current alcohol or drug abuse or dependence;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dutasteride | Drug | 1 |
| Placebo oral capsule | Drug | 2 |
Primary outcome
Rating Scale for Premenstrual Tension (PMTS); Daily symptom rating form (DRF); Visual Analogue Symptom (VAS) self-rating form.
Time frame: Every 2 weeks for the PMTS; daily for the others.
1 secondary outcome
Neuroendocrine response to DEX/crh test; Beck Depression Inventory (BDI)
Time frame: DEX/crf 2x second mth of tx, 1x during luteal ph & 1x during follicular ph.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 12892987Halbreich U, Borenstein J, Pearlstein T, Kahn LS. The prevalence, impairment, impact, and burden of premenstrual dysphoric disorder (PMS/PMDD). Psychoneuroendocrinology. 2003 Aug;28 Suppl 3:1-23. doi: 10.1016/s0306-4530(03)00098-2.
- Background: PubMed 11883723Wittchen H -U, Becker E, Lieb R, Krause P. Prevalence, incidence and stability of premenstrual dysphoric disorder in the community. Psychol Med. 2002 Jan;32(1):119-32. doi: 10.1017/s0033291701004925.
- Background: PubMed 6362441Rubinow DR, Roy-Byrne P. Premenstrual syndromes: overview from a methodologic perspective. Am J Psychiatry. 1984 Feb;141(2):163-72. doi: 10.1176/ajp.141.2.163.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pedro E Martinez, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dutasteride in people with Premenstrual Syndrome and PMS, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rating Scale for Premenstrual Tension (PMTS); Daily symptom rating form (DRF); Visual Analogue Symptom (VAS) self-rating form. (time frame: Every 2 weeks for the PMTS; daily for the others.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00082043, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019.