Treatment of Endometriosis With Norethindrone Acetate ( NA) VS. Gonadotropin- Releasing Hormone (GnRH) Agonist (Lupron Depot 11.25 mg)

NCT00458458 | Unknown Phase 3 DMC

• 1 other identifier: 1R01HD043281
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

(A) Major 1) to compare the effectiveness of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3) in relieving symptoms of endometriosis, 2) to compare bone density in the two treated groups in order to demonstrate that NA does not affect bone density; (B) Minor: 1) To compare the lipid profiles of patients in the two groups to confirm the hypothesis that the effects of NA and GnRH agonists on lipid profiles are similar, 2) To determine whether quality of life, assessed by questionnaire, is better in patients assigned to NA than in patients assigned to GnRH, 3) To determine whether NA has fewer adverse effects than GnRH agonist.

Conditions

Endometriosis; Dysmenorrhea; Dyspareunia

Keywords

Endometriosis; Dysmenorrhea; Pelvic Pain; Period Pain; Menstrual Cramps; Dyspareunia; Norethindrone Acetate; Lupron Depot; Bone Density; Lipid Profile

Outcome Measures

Primary Outcomes (2)

• To compare the effectiveness of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3) in relieving symptoms of endometriosis

  First 24 weeks of treatment

• To compare effect of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3)on bone density

  Bone density with be compared in the two treated groups in order to demonstrate that NA does not affect bone density.

  52 weeks of treatment

Secondary Outcomes (2)

• To compare the effect of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3)on lipid profiles

  Treatment and follow-up

• To determine the effect treatment has on quality of life

  Treatment and follow-up

Study Arms (2)

NA alone

ACTIVE COMPARATOR

Norethindrone Acetate (NA) 5mg taken 1-3 tabs orally every night for duration of treatment

Drug: Norethindrone Acetate (NA)

LD then NA

ACTIVE COMPARATOR

Lupron Depot(LD) given intramuscularly every 12 weeks for total of 24 weeks then switched to Norethindrone Acetate (NA) taken 1-3 tablets orally every night for remainder of treatment

Drug: GnRH Agonist (Lupron Depot)

Interventions

Norethindrone Acetate (NA) DRUG

52 weeks of treatment with Norethindrone Acetate

NA alone

GnRH Agonist (Lupron Depot) DRUG

24 weeks of treatment with Lupron Depot then 28 weeks of treatment with Norethindrone Acetate

LD then NA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• The subject has voluntarily signed the Informed Consent form after having the contents fully explained, after all questions are answered and prior to undergoing any study-related procedures.
• The subject is a pre-menopausal female at least 18 years of age at the time of screening having regular periods (21-42 days intervals) with no menopausal symptoms.
• The subject has a diagnosis of endometriosis made via laparoscopy or laparotomy (operative report will be obtained) and still symptomatic and at least 3 months after surgery have a grade 2 and above according to Biberoglu's pain grade at screening visit (4 weeks prior initiation of treatment) or 4 out of 10 on a visual pain scale (visual analogue)
• Subject in good health, except for endometriosis, or has mild medical conditions that are stable and controlled. The subject has no clinically relevant hepatic, renal, cardiovascular, respiratory, endocrine, metabolic, psychiatric, neurologic (epilepsy), hematolytic (coagulopathy) and/or immunologic disease (on steroids) or disorder.
• A subject who has received any of the hormone therapies (GnRH agonist or danazol or progestin) must meet the minimum washout requirement to be eligible. (GnRH within the last 6 months and with steroids within the last month.) After hormonal therapy has stopped, the subject must have returned to normal for at least two menstrual cycles before baseline time.
• Serum pregnancy and urine qualitative pregnancy tests performed at screening and on baseline must be negative.
• Unless surgical sterile by bilateral tubal ligation or vasectomy of partner, the subject agrees to use a double-barrier method of contraception during the screening period, throughout the 24-week treatment period, such as: condom plus spermicide, diaphragm plus spermicide, sponge plus spermicide, abstinence is an acceptable form of birth control.
• Less than grade III overweight or BMI \<40 kg/M2

You may not qualify if:

• Less than 3 months postpartum and post-lactation at the time of dosing.
• Abnormal laboratory findings considered clinically significant if more than twice the normal range. Abnormal tests will be repeated, and if still high as stated before, subject will be excluded.
• A previous history of significant adverse reactions to hormone, progestin or progesterone and GnRH agonist therapies.
• Abnormal Pap smear in the last 6 months. Subjects with ASCUS (atypical squamous cells of undetermined significance) and are negative for high-risk human papilloma virus (HPV) will be eligible. Subjects that have atypical endocervical cells, and atypical glandular cells are not eligible for this study.
• Subject has a bone density T score less or equal to 2.5, history of nontraumatic fracture, history of spinal surgery, history of fusion of lumbar region, history of severe scoliosis greater than 20 degrees.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead
• State University of New York - Downstate Medical Center: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

SUNY Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

MeSH Terms

Conditions

Endometriosis; Dysmenorrhea; Dyspareunia; Pelvic Pain

Interventions

Norethindrone Acetate; Gonadotropin-Releasing Hormone; Leuprolide

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Genital Diseases, Male; Sexual Dysfunction, Physiological; Male Urogenital Diseases; Sexual Dysfunctions, Psychological; Mental Disorders

Intervention Hierarchy (Ancestors)

Norethindrone; Norpregnenes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Ozgul Muneyyirci-Delale, M.D.

  State University of New York - Downstate Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Division of Reproductive Endocrinology and Infertility

Study Record Dates

• First Submitted: April 9, 2007
• First Posted: April 10, 2007
• Study Start: August 1, 2004
• Primary Completion: December 1, 2012
• Last Updated: October 25, 2012

Record last verified: 2012-10

Locations

US (1)