Premenstrual Dysphoric DisorderPhase 4PMDDNCT00927095
Continuous Oral Contraceptive Treatment in Premenstrual Dysphoric Disorder (PMDD)
A Phase 4 study testing Continuous OC (EE/DROS) and Intermittent OC (EE/DROS) in people with Premenstrual Dysphoric Disorder, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
The purpose of this study is to compare a low dose oral contraceptive (OC) given continuously (every day for three months) with the same low dose oral contraceptive given in an interrupted regimen (one week of inactive placebo pills each month) and with continuous placebo (inactive placebo given every day for three… Read more about this study
- Who is it for?
- Ages 18 to 52 years, women only
- Conditions the study is for
- Premenstrual Dysphoric Disorder
- What is being tested?
- Continuous OC (EE/DROS) and Intermittent OC (EE/DROS)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2008to Jul 2014
- Phase
- Phase 4
- 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 52 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- meets prospective criteria for PMDD, AND
- English speaking and reading skills.
Who cannot join
- current psychiatric disorder other than PMDD,
- history of venous thromboembolism,
- over 35 years of age and obese,
- uncontrolled hypertension or end-organ vascular disease,
- diabetes,
- migraine headache with aura,
Show all 12Show fewer
- breastfeeding or pregnant,
- cigarette smoking,
- family history of premenopausal breast cancer or breast cancer in more than one first degree relative,
- elevated serum potassium levels, use of prescription medications (except stable thyroid supplementation),
- irregular menstrual cycles, OR
- history of: endometriosis, hepatic disease, breast carcinoma, pulmonary embolism or phlebothrombosis, malignant melanoma, cholecystitis or pancreatitis.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina
Chapel Hill, North Carolina, 27599
About this study
Official title: Continuous OC Treatment in PMDD: Steroid Hormone Mechanisms
The purpose of this study is to compare a low dose oral contraceptive (OC) given continuously (every day for three months) with the same low dose oral contraceptive given in an interrupted regimen (one week of inactive placebo pills each month) and with continuous placebo (inactive placebo given every day for three months). The primary hypothesis is that continuous OC will be significantly more effective in reducing premenstrual symptoms compared with either the interrupted OC or continuous placebo.
Read the detailed description
Premenstrual Dysphoric Disorder (PMDD) describes the cyclic appearance of affective symptoms and resultant impairment during the luteal phase of the menstrual cycle. The objective of this trial is to determine if extended oral contraceptive (OC) regimens with eliminated pill-free intervals will successfully prevent the expression of PMDD symptoms. The central hypothesis of this application is that continuous administration of OCs will minimize the destabilizing effects of changing reproductive steroid levels and prevent PMDD symptom emergence. The cause of PMDD is unknown, the morbidity substantial, and the identified treatments limited in their effectiveness, since 40% of PMDD women are non-responders to elective serotonin re-uptake inhibitors (SSRIs). Earlier controlled studies of OCs to treat PMDD failed to find OCs superior to placebo using the traditional 21/7 platform (21 active pills followed by a 7 day pill-free interval (PFI)). Two recent trials of a low dose OC using a 24/4 platform did report greater reductions in premenstrual symptoms relative to placebo, presumably due to the shortened PFI. Despite the apparent efficacy of the 3-day extended dosing of this OC, the placebo response rate was substantial in these studies, resulting in a low effect size. Moreover, no steroid hormone levels were examined in these prior studies. In the absence of hormonal data, inferences about the mechanism of efficacy of extended OCs must remain speculative and untested.
Our proposed research will addresses the critical role of hormonal change in the precipitation of PMDD symptoms before and after treatment with a continuous OC regimen, an interrupted OC regimen (21/7 platform) and continuous placebo. This study will also permit us to examine the role of neurosteroids in PMDD. While acting acutely as anxiolytic positive modulators of the gamma-aminobutyric acid A (GABAA) receptor, these neurosteroids may paradoxically reduce the response of the GABAA receptor and cause irritability (in rats) following either extended exposure or withdrawal. Further, our prior research suggests that elevated levels of or changes in peripheral neurosteroid levels are associated with dysphoric mood symptoms in women with PMDD. Our hypothesis is that changes in neurosteroids modulate symptom severity rather than appearance in PMDD. The results of our study will suggest therapeutic targets and will inform future studies of both PMDD and related affective disorders.
- Conditions
- Premenstrual Dysphoric Disorder
- Being tested
- Continuous OC (EE/DROS), Intermittent OC (EE/DROS), placebo
- Keywords
- PMDD, Oral contraceptives, steroid hormones, neurosteroids
- Medical subject headings
- Premenstrual Dysphoric Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuous OC (EE/DROS)Drug
Also called Yaz
Continuous EE(20ug)+DROS(3mg) daily for 3 months
Intermittent OC (EE/DROS)Drug
Also called Yaz
Intermittent EE(20ug)+DROS(3mg) daily for 21 days each month
placeboDrug
Also called oral placebo
daily placebo
| Study group | Role | What they receive |
|---|---|---|
| Continuous OC (EE/DROS) | Active comparator | Continuous daily oral drospirenone (DROS; 3mg) + ethinyl estradiol (EE; 20ug) Receives: Drug: Continuous OC (EE/DROS) |
| Intermittent OC (EE/DROS) | Active comparator | Interrupted (21 days active - 7 days placebo) oral DROS (20ug)/EE(3mg) Receives: Drug: Intermittent OC (EE/DROS) |
| Placebo | Placebo comparator | Continuous daily oral placebo Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pre-Post Change in Premenstrual Symptom Severity
Pre-post change (pre minus post) in mean premenstrual week severity of the worst emotional symptom as measured using the Daily Record of Severity of Problems items 1-8. Worst symptom for each individual was defined as the symptom in the baseline month demonstrating the highest mean severity during the premenstrual week. Mean premenstrual week severity scores were calculated to correspond to mean ratings; therefore, the mean premenstrual severity values ranged as follows: 1=Not at All, 2=Minimal, 3=Mild, 4=Moderate, 5=Severe, 6=Extreme. The change variable presented here is calculated as follows: "mean rating on the individual's worst symptom during the premenstrual week at baseline" minus "mean rating during the premenstrual week during the last on-treatment cycle". Therefore, higher values on this outcome variable correspond to greater reductions in premenstrual symptoms across the trial.
Measured: monthly
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2009 (estimated)
- Study startJul 2008
- Primary completionJul 2014
- Study completionJul 2014
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 (1)Papers the sponsor has linked to this study.
- Other trials for Premenstrual Dysphoric DisorderStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Susan Girdler, PhD, University of North Carolina, Chapel Hill
- Investigators
- Susan Girdler, PhD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00927095
- Sponsor's protocol ID
- MH081837
- Other IDs
- R01MH081837
- Acronym
- PMDD
- Status last verified
- Jul 2016
- First submitted
- 22 Jun 2009
- Last updated
- 24 Aug 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Eisenlohr-Moul TA, Girdler SS, Johnson JL, Schmidt PJ, Rubinow DR. Treatment of premenstrual dysphoria with continuous versus intermittent dosing of oral contraceptives: Results of a three-arm randomized controlled trial. Depress Anxiety. 2017 Oct;34(10):908-917. doi: 10.1002/da.22673. Epub 2017 Jul 17.
PubMed 28715852
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Continuous OC Treatment in PMDD: Steroid Hormone Mechanisms
- ClinicalTrials.gov ID
- NCT00927095
- Acronym / sponsor ID
- PMDD / MH081837
- Conditions
- Premenstrual Dysphoric Disorder
- Keywords
- PMDD, Oral contraceptives, steroid hormones, neurosteroids
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Jul 2008
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 24 Jun 2009 (estimated)
- Results
- Posted 24 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare a low dose oral contraceptive (OC) given continuously (every day for three months) with the same low dose oral contraceptive given in an interrupted regimen (one week of inactive placebo pills each month) and with continuous placebo (inactive placebo given every day for three months). The primary hypothesis is that continuous OC will be significantly more effective in reducing premenstrual symptoms compared with either the interrupted OC or continuous placebo.
Detailed description
Premenstrual Dysphoric Disorder (PMDD) describes the cyclic appearance of affective symptoms and resultant impairment during the luteal phase of the menstrual cycle. The objective of this trial is to determine if extended oral contraceptive (OC) regimens with eliminated pill-free intervals will successfully prevent the expression of PMDD symptoms. The central hypothesis of this application is that continuous administration of OCs will minimize the destabilizing effects of changing reproductive steroid levels and prevent PMDD symptom emergence. The cause of PMDD is unknown, the morbidity substantial, and the identified treatments limited in their effectiveness, since 40% of PMDD women are non-responders to elective serotonin re-uptake inhibitors (SSRIs). Earlier controlled studies of OCs to treat PMDD failed to find OCs superior to placebo using the traditional 21/7 platform (21 active pills followed by a 7 day pill-free interval (PFI)). Two recent trials of a low dose OC using a 24/4 platform did report greater reductions in premenstrual symptoms relative to placebo, presumably due to the shortened PFI. Despite the apparent efficacy of the 3-day extended dosing of this OC, the placebo response rate was substantial in these studies, resulting in a low effect size. Moreover, no steroid hormone levels were examined in these prior studies. In the absence of hormonal data, inferences about the mechanism of efficacy of extended OCs must remain speculative and untested.
Our proposed research will addresses the critical role of hormonal change in the precipitation of PMDD symptoms before and after treatment with a continuous OC regimen, an interrupted OC regimen (21/7 platform) and continuous placebo. This study will also permit us to examine the role of neurosteroids in PMDD. While acting acutely as anxiolytic positive modulators of the gamma-aminobutyric acid A (GABAA) receptor, these neurosteroids may paradoxically reduce the response of the GABAA receptor and cause irritability (in rats) following either extended exposure or withdrawal. Further, our prior research suggests that elevated levels of or changes in peripheral neurosteroid levels are associated with dysphoric mood symptoms in women with PMDD. Our hypothesis is that changes in neurosteroids modulate symptom severity rather than appearance in PMDD. The results of our study will suggest therapeutic targets and will inform future studies of both PMDD and related affective disorders.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Continuous OC (EE/DROS) | Active comparator | Drug: Continuous OC (EE/DROS)Continuous daily oral drospirenone (DROS; 3mg) + ethinyl estradiol (EE; 20ug) |
| Intermittent OC (EE/DROS) | Active comparator | Drug: Intermittent OC (EE/DROS)Interrupted (21 days active - 7 days placebo) oral DROS (20ug)/EE(3mg) |
| Placebo | Placebo comparator | Drug: placeboContinuous daily oral placebo |
Who may qualify
- Ages
- 18 to 52 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- meets prospective criteria for PMDD, AND
- English speaking and reading skills.
Key exclusion criteria (12 listed)
- current psychiatric disorder other than PMDD,
- history of venous thromboembolism,
- over 35 years of age and obese,
- uncontrolled hypertension or end-organ vascular disease,
- diabetes,
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 |
|---|---|---|
| Continuous OC (EE/DROS)Also: YazContinuous EE(20ug)+DROS(3mg) daily for 3 months | Drug | Continuous OC (EE/DROS) |
| Intermittent OC (EE/DROS)Also: YazIntermittent EE(20ug)+DROS(3mg) daily for 21 days each month | Drug | Intermittent OC (EE/DROS) |
| placeboAlso: oral placebodaily placebo | Drug | Placebo |
Primary outcome
Pre-Post Change in Premenstrual Symptom Severity
Time frame: monthly
Pre-post change (pre minus post) in mean premenstrual week severity of the worst emotional symptom as measured using the Daily Record of Severity of Problems items 1-8. Worst symptom for each individual was defined as the symptom in the baseline month demonstrating the highest mean severity during the premenstrual week. Mean premenstrual week severity scores were calculated to correspond to mean ratings; therefore, the mean premenstrual severity values ranged as follows: 1=Not at All, 2=Minimal, 3=Mild, 4=Moderate, 5=Severe, 6=Extreme. The change variable presented here is calculated as follows: "mean rating on the individual's worst symptom during the premenstrual week at baseline" minus "mean rating during the premenstrual week during the last on-treatment cycle". Therefore, higher values on this outcome variable correspond to greater reductions in premenstrual symptoms across the trial.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28715852Eisenlohr-Moul TA, Girdler SS, Johnson JL, Schmidt PJ, Rubinow DR. Treatment of premenstrual dysphoria with continuous versus intermittent dosing of oral contraceptives: Results of a three-arm randomized controlled trial. Depress Anxiety. 2017 Oct;34(10):908-917. doi: 10.1002/da.22673. Epub 2017 Jul 17.
- Individual participant dataSharing planned: Undecided
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Premenstrual Dysphoric Disorder ( PMDD)
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.
Susan Girdler, PhD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Continuous OC (EE/DROS) and Intermittent OC (EE/DROS) in people with Premenstrual Dysphoric Disorder, run by University of North Carolina, Chapel Hill 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 2 inclusion and 12 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 24 Aug 2016. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 24 Aug 2016). 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?
Pre-Post Change in Premenstrual Symptom Severity (time frame: monthly). 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 NCT00927095, which also lists 1 linked publication.
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 24 Aug 2016.