Treatment of Menstrually Related Disorders With Continuous v. Interrupted Oral Contraceptives

NCT00089414 | Terminated Phase 2 Results

• 2 other identifiers: 04022104-M-0221
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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. 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). ...

Conditions

Premenstrual Syndrome; PMS; Premenstrual Dysphoric Disorder; PMDD; Depression

Keywords

Depression; Menstrual Cycle; Gonadal Steroids; Ethinyl Estradiol; Drospirenone; Menstrually Related Mood Disorder; MRMD

Outcome Measures

Primary Outcomes (1)

• 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.

  Every 2 weeks for 3 months

Secondary Outcomes (2)

• Change in Clinical Global Impression Scale (CGI) Factors Associated With Premenstrual Symptoms.

  Every 2 wks for 3 months

• Change in Beck Depression Inventory (BDI) Factors Associated With Premenstrual Symptoms

  Every 2 weeks for 3 months

Study Arms (3)

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.

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).

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.

Drug: Ethinyl Estradiol/Drospirenone; Drug: CDB 2914

Interventions

Ethinyl Estradiol/Drospirenone DRUG

Drug administered dependent upon arm.

Also known as: Yasmin

1; 2; 3

Placebo DRUG

2

CDB 2914 DRUG

Also known as: Progesterone antagonist

3

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects who meet criteria for MRMD are healthy (by physical exam, normal pelvic exam and pap smear, and normal lab values) and medication free will be included in this study.
• Oral contraceptives (and CDB-2914 in arm #3) will not be administered to any subject with significant clinical or laboratory abnormalities.

You may not qualify if:

• 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.
• 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;

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 6686333 BACKGROUND

• Schmidt 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.

  PMID: 2011161 BACKGROUND

• Muse 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.

  PMID: 6387488 BACKGROUND

MeSH Terms

Conditions

Premenstrual Syndrome; Premenstrual Dysphoric Disorder; Depression

Interventions

drospirenone and ethinyl estradiol combination; ulipristal

Condition Hierarchy (Ancestors)

Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Limitations and Caveats

Protocol terminated after receiving information from manufacturer (Pharma) that CDB-2914 crosses the blood-brain barrier, invalidating Arm #3 due to potential CNS effect of the compound on behavior.

Results Point of Contact

• Title: Pedro E. Martinez, M.D., Principal Investigator
• Organization: Behavioral Endocrinology Branch/National Institute of Mental Health/NIH

martinep@mail.nih.gov

301-402-0615

Study Officials

• Pedro E Martinez, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2004
• First Posted: August 5, 2004
• Study Start: July 1, 2004
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: August 25, 2017
• Results First Posted: January 2, 2017

Record last verified: 2017-07

Locations

US (1)