NIH Clinical Research Studies

Protocol Number: 02-CH-0287

Active Accrual, Protocols Recruiting New Patients

Title:
Treatment of Leiomyomata with the Selective Progesterone Receptor Modulator CDB-2914
Number:
02-CH-0287
Summary:
This study will evaluate the selective progesterone receptor modulator CDB-2914 for treating uterine fibroids in pre-menopausal women. It will compare fibroid size, hormone levels and symptoms in women who take CDB-2914 with that of women who take a placebo (an inactive substance). The study will also evaluate the endocrine effects of chronic daily administration of CDB-2914, including possible effects on the menstrual cycle and on adrenal gland function.

Pre-menopausal women between 33 and 50 years of age who have predictable menstrual cycles of normal length and uterine fibroids of at least 2 cm in size may be eligible for this study. Only women who need and want hysterectomy for treatment of fibroids will be enrolled. Candidates will be screened with a medical history and physical examination, including a breast and pelvic examination, blood and urine tests, and completion of a questionnaire about quality of life. They will be taught to use a kit to test their urine for LH, a hormone produced in large amounts just before ovulation, and will be given a calendar to record the LH surge, as well as any spotting, bleeding, or other symptoms. The study will take place over four menstrual cycles, after which hysterectomy will be performed. Participants will undergo the following procedures:

- First (pre-treatment) cycle: Participants will undergo magnetic resonance imaging (MRI) and a special ultrasound test called saline hysterosonogram. MRI uses radio waves and a magnetic field to image body tissues. The subject lies in a narrow metal cylinder (the scanner) for about an hour during the imaging. A contrast material is injected into a vein to brighten the images. The saline hysterosonogram involves placing a speculum in the vagina, as if for a Pap test, and then putting a very small amount of liquid inside the uterus, using a small plastic tube. An ultrasound examination is then done by inserting a probe into the vagina. The probe emits and receives sound waves that are used to form a picture of the internal structures.

- Second through fourth menstrual cycles - Participants will have a pregnancy test on the first or second day of each cycle. Those who are not pregnant will take CDB-2914 once a day for three menstrual cycles, or up to 102 days if the cycles are irregular. At specific times during the cycles, subject will have blood tests to measure the effect of CDB-2914 on hormones, blood count, blood chemistries, and liver function, and ultrasound tests to check the number and size of follicles in the ovaries. They will test their urine to detect the LH surge and will have additional hormone blood tests. At three times during the study-during the first, second and third menstrual cycles-subjects will bring a 24-hour urine collection to the clinic for measurements of cortisol and adrenal gland function. A transvaginal ultrasound study will be repeated after 4 to 6 weeks of treatment to check fibroid growth. A repeat saline hysterosonogram and MRI will be done within 2 weeks of surgery to count the number of fibroids and measure their size.

Women who have completed the study to the end of the four menstrual cycles and still require hysterectomy will stop taking CDB-2914. They will complete another quality of life questionnaire. Their blood levels of CDB-2914 will be measured, and they will have a hysterectomy, in which the uterus, and possibly the ovaries, will be removed. Subjects will be discharged from the hospital 2 to 4 days after surgery and will return to the clinic for post-operative evaluation after 4 to 6 weeks.

Sponsoring Institute:
National Institute of Child Health and Human Development (NICHD)
Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Female
Referral Letter Required: Yes
Population Exclusion(s): Male

Children

Eligibility Criteria:
GENERAL INCLUSION CRITERIA:

Women receiving insulin or thyroid hormone replacement may participate if well-controlled; use of vitamins and calcium under RDA is allowed.

Female gender-to evaluate effects in the target population for clinical trials.

In good health. Chronic medication use is acceptable except for glucocorticoid use. Other chronic medication use may be acceptable at the discretion of the research team. Interval use of over-the counter drugs is acceptable but must be recorded.

Menstrual cycles of 24 - 35 days.

Hemoglobin greater than 10 g/dL.

Willing and able to comply with study requirements.

Age 33 to 50.

Using mechanical (condoms, diaphragms), sterilization or abstinence methods of contraception for the duration of the study.

Negative urine pregnancy test.

BMI less than or equal to 30.

Able to read and speak English fluently to allow accurate self-administration of medication, recording of symptoms and unassisted completion of questionnaire.

Normal glomerular filtration rate.

Liver function tests within 130% of upper limit.

INCLUSION CRITERIA FOR WOMEN WITH LEIOMYOMA:

History of uterine leiomyoma causing symptoms of bleeding, pressure, or pain, as defined by the ACOG practice bulletin (ACOG Practice Bulletin 1994):

Excessive uterine bleeding will be evidenced by either of the following-profuse bleeding with flooding or clots or repetitive periods lasting for more than 8 days; or anemia due to acute or chronic blood loss; OR

Pelvic discomfort caused by leiomyomata, either acute and severe or chronic lower abdominal or low back pressure or bladder pressure with urinary frequency not due to urinary tract infection.

Uterine leiomyoma(ta) of at least 2 cm size.

No desire for fertility; willing to undergo hysterectomy.

GENERAL EXCLUSION CRITERIA:

Significant abnormalities in the history, physical or laboratory examination.

Pregnancy.

Lactation.

Use of oral, injectable or inhaled glucocorticoids or megesterol within the last year.

Unexplained vaginal bleeding.

History of malignancy within the past 5 years.

Use of estrogen or progesterone-containing compounds, such as oral contraceptives and hormone replacement therapy, within 8 weeks of study entry, including transdermal, injectable, vaginal and oral preparations.

Use of agents known to induct hepatic P450 enzymes; use of imidazoles.

Current use of GnRH analogs or other compounds that affect menstrual cyclicity.

FSH greater than 20 IU/mL.

Significant medical disorders.

Cervical dysplasia.

Need for interval use of narcotics.

Abnormal adnexal/ovarian mass.

Intrauterine device.

EXCLUSION CRITERIA FOR WOMEN WITH FIBROIDS:

Use of herbal medication having estrogenic or antiestrogenic effects within the past 3 months.

Contradiction to anesthesia

Genetic causes of leiomyomata.

Previous participation in the study.

Known recent rapid growth of fibroids, defined as a doubling in size in six months.

Special Instructions: Currently Not Provided
Keywords:
Endometrium
Progesterone
Estrogen
Leiomyoma
Recruitment Keywords:
Uterine Leiomyoma
Uterine Fibroids
Fibroids
Conditions:
Leiomyoma
Investigational Drug(s):
CDB-2914
Investigational Device(s):
None

Contacts:
Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:
Batista MC, Cartledge TP, Zellmer AW, Merino MJ, Axiotis C, Loriaux DL, Nieman LK. Delayed endometrial maturation induced by daily administration of the antiprogestin RU 486: a potential new contraceptive strategy. Am J Obstet Gynecol. 1992 Jul;167(1):60-5. PMID: 1442957

Cadepond F, Ulmann A, Baulieu EE. RU486 (mifepristone): mechanisms of action and clinical uses. Annu Rev Med. 1997;48:129-56. Review. PMID: 9046951

Burroughs KD, Howe SR, Okubo Y, Fuchs-Young R, LeRoith D, Walker CL. Dysregulation of IGF-I signaling in uterine leiomyoma.

J Endocrinol. 2002 Jan;172(1):83-93. PMID: 11786376

Active Accrual, Protocols Recruiting New Patients

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