A Phase 4 interventional study of Continuous OC (EE/DROS) and Intermittent OC (EE/DROS) in Premenstrual Dysphoric Disorder, sponsored by University of North Carolina, Chapel Hill. Completed at 1 site in United States. Open to female participants aged 18 Years to 52 Years. Per ClinicalTrials.gov, last updated 2016-08-24.
Sponsored by University of North Carolina, Chapel Hill · Phase 4, Interventional, and Treatment
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.
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.
41 studies on the registry are indexed under Premenstrual Dysphoric Disorder; 9 are open to participants now.
This study's enrollment of 67 is above the median of 58 across 32 interventional studies indexed under Premenstrual Dysphoric Disorder.
Browse Premenstrual Dysphoric Disorder studies →University of North Carolina, Chapel Hill is the lead sponsor of 1,340 studies on the registry; 133 are open to participants now.
Of its 155 completed or terminated interventional studies of FDA-regulated products, 136 (88%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Continuous daily oral drospirenone (DROS; 3mg) + ethinyl estradiol (EE; 20ug)
Drug: Continuous OC (EE/DROS)
Interrupted (21 days active - 7 days placebo) oral DROS (20ug)/EE(3mg)
Drug: Intermittent OC (EE/DROS)
Continuous daily oral placebo
Drug: placebo
Continuous EE(20ug)+DROS(3mg) daily for 3 months
Also known as: Yaz
Intermittent EE(20ug)+DROS(3mg) daily for 21 days each month
Also known as: Yaz
daily placebo
Also known as: oral placebo
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.
Time frame: monthly
| Milestone | Continuous Low Dose Oral Contraceptive | Interrupted Low Dose Oral Contraceptive (21/7 Platform) | Continuous Placebo |
|---|---|---|---|
| Started | 22 | 21 | 24 |
| Completed | 16 | 17 | 22 |
| Not completed | 6 | 4 | 2 |
| Withdrew: Adverse event | 3 | 1 | 0 |
| Withdrew: Withdrawal by subject | 2 | 1 | 1 |
| Withdrew: Physician decision | 1 | 2 | 1 |
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.
| units on a scale | Continuous Low Dose Oral Contraceptive | Interrupted Low Dose Oral Contraceptive (21/7 Platform) | Continuous Placebo |
|---|---|---|---|
| Pre-Post Change in Premenstrual Symptom Severity | 1.93 ± .22 | 1.73 ± .22 | 1.64 ± .19 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Continuous Low Dose Oral Contraceptive | — | 0/22 (0%) | 22/22 (100%) |
| Interrupted Low Dose Oral Contraceptive (21/7 Platform) | — | 0/21 (0%) | 21/21 (100%) |
| Continuous Placebo | — | 0/24 (0%) | 24/24 (100%) |
| Event | Continuous Low Dose Oral Contraceptive | Interrupted Low Dose Oral Contraceptive (21/7 Platform) | Continuous Placebo |
|---|---|---|---|
| Headache, Not MigraineNervous system disorders | 10/22 | 16/21 | 20/24 |
| FatigueGeneral disorders | 14/22 | 17/21 | 15/24 |
| Low MoodPsychiatric disorders | 17/22 | 13/21 | 17/24 |
| GI SymptomsGastrointestinal disorders | 13/22 | 16/21 | 13/24 |
| Breast TendernessReproductive system and breast disorders | 15/22 | 15/21 | 18/24 |
| IrritabilityPsychiatric disorders | 14/22 | 14/21 | 15/24 |
| Anxious SymptomsPsychiatric disorders | 8/22 | 8/21 | 15/24 |
| Leg or Calf DiscomfortMusculoskeletal and connective tissue disorders | 10/22 | 13/21 | 9/24 |
| BloatingGastrointestinal disorders | 4/22 | 11/21 | 10/24 |
| SpottingReproductive system and breast disorders | 11/22 | 10/21 | 4/24 |
| Age, Continuous(years) | Continuous Low Dose Oral Contraceptive | Interrupted Low Dose Oral Contraceptive (21/7 Platform) | Continuous Placebo | Total |
|---|---|---|---|---|
| Mean | 33.2 ± 8.1 | 32.2 ± 8.6 | 32.1 ± 6.7 | 32.5 ± 7.7 |
| Sex: Female, Male(Participants) | Continuous Low Dose Oral Contraceptive | Interrupted Low Dose Oral Contraceptive (21/7 Platform) | Continuous Placebo | Total |
|---|---|---|---|---|
| Female | 22 | 21 | 24 | 67 |
| Male | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Continuous Low Dose Oral Contraceptive | Interrupted Low Dose Oral Contraceptive (21/7 Platform) | Continuous Placebo | Total |
|---|---|---|---|---|
| United States | 22 | 21 | 24 | 67 |
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Premenstrual Dysphoric Disorder→
University of North Carolina, Chapel Hill