Premenstrual SyndromePhase 2NCT00089414
Treatment of Menstrually Related Disorders With Continuous v. Interrupted Oral Contraceptives
A Phase 2 study testing Ethinyl Estradiol/Drospirenone and CDB 2914 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 determine whether uninterrupted treatment with birth control pills over several menstrual cycles prevents severe premenstrual syndrome (PMDD). Previous studies have shown that the hormones estrogen and progesterone regulate mood in women with MRMD. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Premenstrual Syndrome, PMS, Premenstrual Dysphoric Disorder
- What is being tested?
- Ethinyl Estradiol/Drospirenone and CDB 2914
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2004to Jun 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
None listed.
Who cannot join
- Any patient with a current axis I psychiatric diagnosis will be excluded from participating in this protocol.
- Subjects taking psychotropic agents (e.g. antidepressants, anxiolytics or mood stabilizers) will likewise be excluded from the study.
- Women who have received glucocorticoid or megestrol therapy within the last year (and thus may experience residual suppression of the compensatory HPA axis response to CDB-2914-induced glucocorticoid receptor antagonism) will be also excluded, albeit almost entirely on theoretical grounds.
- Women who have any chronic medical conditions or are taking medications will be excluded.
- Women who have a medical condition or are taking any chronic medications that may increase serum potassium levels will also be excluded.
- Those patients who would be uncomfortable with extending the length of their menstrual cycles will not be enrolled in this study and will either be offered participation in another study or an outside referral for treatment in the community.
Show all 21Show fewer
- The following conditions will constitute contraindications to treatment with continuous oral contraception or the use of the progesterone antagonist, CDB-2914, and will preclude a patient's participating in this protocol:
- history of endometriosis, or recent, rapid growth of uterine fibroid tumors (defined as doubling in size in six month period);
- diagnosis of ill-defined, obscure pelvic lesions, particularly undiagnosed ovarian enlargement;
- hepatic disease as manifested by abnormal liver function tests;
- history of breast carcinoma;
- history of pulmonary embolism or phlebothrombosis;
- undiagnosed vaginal bleeding;
- porphyria;
- history of malignant melanoma;
- history of cholecystitis or pancreatitis;
- history of hypercholesterolemia, hypertension, diabetes, or renal disease;
- recurrent migraine headaches (greater than or equal to 3 per year) in women 35 or older;
- pregnancy or lactation;
- cigarette smoking in women 35 or older, or more than 10 cigarettes per day in women under 35; or
- use of oral, injectable, or inhaled glucocorticoids or megestrol within the last year.
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 Treatment of Menstrually-Related Mood Disorders With Extended Versus Interrupted Oral Contraceptives
This study will determine whether uninterrupted treatment with birth control pills over several menstrual cycles prevents severe premenstrual syndrome (PMDD).
Previous studies have shown that the hormones estrogen and progesterone regulate mood in women with MRMD. This study will use various treatment regimens with birth control pills and placebo (sugar pill) to clarify the relationships among estrogen and progesterone, the menstrual cycle, and mood.
Read more
Healthy women between 18 and 45 years of age who menstruate may be eligible for this 15-week study. Candidates are screened with a physical examination, blood and urine tests, an electrocardiogram, and 3 months of symptoms ratings to confirm MRMD.
Participants are randomly assigned to one of three treatment groups. Group 1 takes a birth control pill every day and on three occasions takes a placebo capsule. Group 2 takes a birth control pill most but not all days and on three occasions takes a placebo capsule. Group 3 takes a birth control pill every day and on three occasions takes another medication called CDB-2914 that causes menstrual bleeding to occur.
Participants come to the NIH clinic every other week for blood tests and measurement of vital signs (blood pressure, pulse, and temperature) and to complete symptoms ratings scales. Subjects who develop breakthrough bleeding (menstruation earlier than expected) will have a transvaginal ultrasound. For this procedure, a probe is inserted into the vagina for about 10 minutes. The probe gives off and receives sound waves that can be used to form a picture of the endometrium (lining of the uterus).
...
Read the detailed description
Results from previous protocols (#90-M-0088 and 92-M-0174) have demonstrated that women with menstrually-related mood disorder (MRMD), but not women lacking this disorder, experience mood deterioration within approximately one to two weeks after exposure to either estradiol or progesterone in the context of gonadal suppression (induced by use of the depot gonadotropin releasing hormone agonist leuprolide acetate). Preliminary results of protocol 00-M-0103 suggest that this hormone-induced depression occurs consequent to changes in gonadal steroid levels and not to simple exposure to basal levels above a critical threshold. Additionally, continued administration of hormone for three months resulted in no further symptoms subsequent to the initial precipitated episode. These data suggest the potential therapeutic benefit of extended oral contraceptive (OC) regimens with reduced pill-free intervals in MRMD to minimize the mood destabilizing effects of changing hormone levels. In this protocol we examine whether the effects of 15 weeks of continuous oral contraceptive administration causes a remission of symptoms in women with MRMD.
- Conditions
- Premenstrual Syndrome, PMS, Premenstrual Dysphoric Disorder, PMDD, Depression
- Being tested
- Ethinyl Estradiol/Drospirenone, Placebo, CDB 2914
- Keywords
- Depression, Menstrual Cycle, Gonadal Steroids, Ethinyl Estradiol, Drospirenone, Menstrually Related Mood Disorder, MRMD
- Medical subject headings
- Premenstrual Syndrome, Premenstrual Dysphoric Disorder, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ethinyl Estradiol/DrospirenoneDrug
Also called Yasmin
Drug administered dependent upon arm.
PlaceboDrug
CDB 2914Drug
Also called Progesterone antagonist
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Treatment arm # 1 consists of the continuous administration of Yasmin oral contraceptive (a combination of 30 µg of ethinyl estradiol and 3 mg of drospirenone) for 15 weeks starting on day 2 to 5 of the first menstrual cycle. Receives: Drug: Ethinyl Estradiol/Drospirenone |
| 2 | Active comparator | Treatment arm # 2 (interrupted Yasmin administration) will be identical to arm # 1 with the exception that the continuous administration of Yasmin will be interrupted by the substitution of placebo for Yasmin for one week during weeks 3, 8, and 14 of the study. The women participating in this treatment arm will experience episodes of menstruation after Yasmin withdrawal (when they are on placebo). Receives: Drug: Ethinyl Estradiol/Drospirenone; Drug: Placebo |
| 3 | Active comparator | Yasmin oral contraceptive; CDB 2914 progesterone antagonist. Treatment arm # 3 is identical to treatment arm # 1 with the exception that the continuous administration of Yasmin will also include the administration of progesterone antagonist CDB-2914 during weeks 3, 8, and 14. Menses is anticipated to occur within 2-3 days of CDB-2914 administration. Women in treatment arms # 3 and # 1 will be exposed to continuous levels of Yasmin, but due to the local effects of the progesterone antagonist on the endometrium, women in arm # 3 will experience menses. Receives: Drug: Ethinyl Estradiol/Drospirenone; Drug: CDB 2914 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Premenstrual Tension Syndrome Scale (PMTS) Factors Associated With Premenstrual Symptoms.
The PMTS observer scales assess symptoms in ten different domains including irritability-hostility; tension; efficiency; dysphoria; moodiness; motor coordination; mental-cognitive functioning; eating habits; sexual drive and activity; physical symptoms and social impairment. They have been used to measure premenstrual symptom severity and response to treatment in several clinical trials and prevalence studies. Score ranges from no symptoms to severe symptoms on a scale of 0 to 6, with 0 being no symptoms and 6 being severely symptomatic.
Measured: Every 2 weeks for 3 months
Secondary outcomes (2)
Change in Clinical Global Impression Scale (CGI) Factors Associated With Premenstrual Symptoms.
The CGI was developed for use in NIMH-sponsored clinical trials to provide a brief, stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication.1 The CGI provides an overall clinician-determined summary measure that takes into account all available information, including a knowledge of the patient's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the patient's ability to function. The CGI actually comprises two companion one-item measures evaluating the following: (a) severity of psychopathology from 1 to 7 and (b) change from the initiation of treatment on a similar seven-point scale, with 1 being normal/more improved and 7 being severe/worse.
Measured: Every 2 wks for 3 months
Change in Beck Depression Inventory (BDI) Factors Associated With Premenstrual Symptoms
The Beck Depression Inventory (BDI)is a 21-question multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depression. Total scores are interpreted per these ranges:
0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression.
Measured: Every 2 weeks for 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2004 (estimated)
- Study startJul 2004
- Primary completionJun 2010
- Study completionJun 2010
Why it stopped: Informed by manufacturer that CDB-2914 crosses blood-brain barrier invalidating Arm #3 of protocol.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 5 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
- NCT00089414
- Sponsor's protocol ID
- 040221
- Other IDs
- 04-M-0221
- Status last verified
- Jul 2017
- First submitted
- 4 Aug 2004
- Last updated
- 25 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Backstrom T, Sanders D, Leask R, Davidson D, Warner P, Bancroft J. Mood, sexuality, hormones, and the menstrual cycle. II. Hormone levels and their relationship to the premenstrual syndrome. Psychosom Med. 1983 Dec;45(6):503-7. doi: 10.1097/00006842-198312000-00004.
PubMed 6686333Schmidt PJ, Nieman LK, Grover GN, Muller KL, Merriam GR, Rubinow DR. Lack of effect of induced menses on symptoms in women with premenstrual syndrome. N Engl J Med. 1991 Apr 25;324(17):1174-9. doi: 10.1056/NEJM199104253241705.
PubMed 2011161Muse KN, Cetel NS, Futterman LA, Yen SC. The premenstrual syndrome. Effects of "medical ovariectomy". N Engl J Med. 1984 Nov 22;311(21):1345-9. doi: 10.1056/NEJM198411223112104.
PubMed 6387488
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Treatment of Menstrually-Related Mood Disorders With Extended Versus Interrupted Oral Contraceptives
- ClinicalTrials.gov ID
- NCT00089414
- Acronym / sponsor ID
- 040221
- Conditions
- Premenstrual Syndrome, PMS, Premenstrual Dysphoric Disorder, PMDD, Depression
- Keywords
- Depression, Menstrual Cycle, Gonadal Steroids, Ethinyl Estradiol, Drospirenone, Menstrually Related Mood Disorder, MRMD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Informed by manufacturer that CDB-2914 crosses blood-brain barrier invalidating Arm #3 of protocol.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- Jul 2004
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 5 Aug 2004 (estimated)
- Results
- Posted 2 Jan 2017
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 determine whether uninterrupted treatment with birth control pills over several menstrual cycles prevents severe premenstrual syndrome (PMDD).
Previous studies have shown that the hormones estrogen and progesterone regulate mood in women with MRMD. This study will use various treatment regimens with birth control pills and placebo (sugar pill) to clarify the relationships among estrogen and progesterone, the menstrual cycle, and mood.
Healthy women between 18 and 45 years of age who menstruate may be eligible for this 15-week study. Candidates are screened with a physical examination, blood and urine tests, an electrocardiogram, and 3 months of symptoms ratings to confirm MRMD.
Participants are randomly assigned to one of three treatment groups. Group 1 takes a birth control pill every day and on three occasions takes a placebo capsule. Group 2 takes a birth control pill most but not all days and on three occasions takes a placebo capsule. Group 3 takes a birth control pill every day and on three occasions takes another medication called CDB-2914 that causes menstrual bleeding to occur.
Participants come to the NIH clinic every other week for blood tests and measurement of vital signs (blood pressure, pulse, and temperature) and to complete symptoms ratings scales. Subjects who develop breakthrough bleeding (menstruation earlier than expected) will have a transvaginal ultrasound. For this procedure, a probe is inserted into the vagina for about 10 minutes. The probe gives off and receives sound waves that can be used to form a picture of the endometrium (lining of the uterus).
...
Detailed description
Results from previous protocols (#90-M-0088 and 92-M-0174) have demonstrated that women with menstrually-related mood disorder (MRMD), but not women lacking this disorder, experience mood deterioration within approximately one to two weeks after exposure to either estradiol or progesterone in the context of gonadal suppression (induced by use of the depot gonadotropin releasing hormone agonist leuprolide acetate). Preliminary results of protocol 00-M-0103 suggest that this hormone-induced depression occurs consequent to changes in gonadal steroid levels and not to simple exposure to basal levels above a critical threshold. Additionally, continued administration of hormone for three months resulted in no further symptoms subsequent to the initial precipitated episode. These data suggest the potential therapeutic benefit of extended oral contraceptive (OC) regimens with reduced pill-free intervals in MRMD to minimize the mood destabilizing effects of changing hormone levels. In this protocol we examine whether the effects of 15 weeks of continuous oral contraceptive administration causes a remission of symptoms in women with MRMD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Ethinyl Estradiol/DrospirenoneTreatment arm # 1 consists of the continuous administration of Yasmin oral contraceptive (a combination of 30 µg of ethinyl estradiol and 3 mg of drospirenone) for 15 weeks starting on day 2 to 5 of the first menstrual cycle. |
| 2 | Active comparator | Drug: Ethinyl Estradiol/Drospirenone, Drug: PlaceboTreatment arm # 2 (interrupted Yasmin administration) will be identical to arm # 1 with the exception that the continuous administration of Yasmin will be interrupted by the substitution of placebo for Yasmin for one week during weeks 3, 8, and 14 of the study. The women participating in this treatment arm will experience episodes of menstruation after Yasmin withdrawal (when they are on placebo). |
| 3 | Active comparator | Drug: Ethinyl Estradiol/Drospirenone, Drug: CDB 2914Yasmin oral contraceptive; CDB 2914 progesterone antagonist. Treatment arm # 3 is identical to treatment arm # 1 with the exception that the continuous administration of Yasmin will also include the administration of progesterone antagonist CDB-2914 during weeks 3, 8, and 14. Menses is anticipated to occur within 2-3 days of CDB-2914 administration. Women in treatment arms # 3 and # 1 will be exposed to continuous levels of Yasmin, but due to the local effects of the progesterone antagonist on the endometrium, women in arm # 3 will experience menses. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (21 listed)
- Any patient with a current axis I psychiatric diagnosis will be excluded from participating in this protocol.
- Subjects taking psychotropic agents (e.g. antidepressants, anxiolytics or mood stabilizers) will likewise be excluded from the study.
- Women who have received glucocorticoid or megestrol therapy within the last year (and thus may experience residual suppression of the compensatory HPA axis response to CDB-2914-induced glucocorticoid receptor antagonism) will be also excluded, albeit almost entirely on theoretical grounds.
- Women who have any chronic medical conditions or are taking medications will be excluded.
- Women who have a medical condition or are taking any chronic medications that may increase serum potassium levels will also be excluded.
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 |
|---|---|---|
| Ethinyl Estradiol/DrospirenoneAlso: YasminDrug administered dependent upon arm. | Drug | 1, 2, 3 |
| Placebo | Drug | 2 |
| CDB 2914Also: Progesterone antagonist | Drug | 3 |
Primary outcome
Change in Premenstrual Tension Syndrome Scale (PMTS) Factors Associated With Premenstrual Symptoms.
Time frame: Every 2 weeks for 3 months
The PMTS observer scales assess symptoms in ten different domains including irritability-hostility; tension; efficiency; dysphoria; moodiness; motor coordination; mental-cognitive functioning; eating habits; sexual drive and activity; physical symptoms and social impairment. They have been used to measure premenstrual symptom severity and response to treatment in several clinical trials and prevalence studies. Score ranges from no symptoms to severe symptoms on a scale of 0 to 6, with 0 being no symptoms and 6 being severely symptomatic.
2 secondary outcomes
Change in Clinical Global Impression Scale (CGI) Factors Associated With Premenstrual Symptoms.
Time frame: Every 2 wks for 3 months
Change in Beck Depression Inventory (BDI) Factors Associated With Premenstrual Symptoms
Time frame: Every 2 weeks for 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 6686333Backstrom T, Sanders D, Leask R, Davidson D, Warner P, Bancroft J. Mood, sexuality, hormones, and the menstrual cycle. II. Hormone levels and their relationship to the premenstrual syndrome. Psychosom Med. 1983 Dec;45(6):503-7. doi: 10.1097/00006842-198312000-00004.
- Background: PubMed 2011161Schmidt PJ, Nieman LK, Grover GN, Muller KL, Merriam GR, Rubinow DR. Lack of effect of induced menses on symptoms in women with premenstrual syndrome. N Engl J Med. 1991 Apr 25;324(17):1174-9. doi: 10.1056/NEJM199104253241705.
- Background: PubMed 6387488Muse KN, Cetel NS, Futterman LA, Yen SC. The premenstrual syndrome. Effects of "medical ovariectomy". N Engl J Med. 1984 Nov 22;311(21):1345-9. doi: 10.1056/NEJM198411223112104.
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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 2 study testing Ethinyl Estradiol/Drospirenone and CDB 2914 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 0 inclusion and 21 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: stopped early, as of the sponsor's last update on 25 Aug 2017. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Premenstrual Tension Syndrome Scale (PMTS) Factors Associated With Premenstrual Symptoms. (time frame: Every 2 weeks for 3 months). 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 NCT00089414, 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 25 Aug 2017.