GnRH-a for Ovarian Protection During CYC Therapy for Rheumatic Diseases

Condition(s) targeted: Lupus Erythematosus, Systemic; Systemic Vasculitis; Isolated Angiitis of Central Nervous System; Lung Disease With Systemic Sclerosis; Lung Disease Interstitial Diffuse

Intervention: depot leuprolide acetate 3.75 mg (Drug); Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Joseph Mccune

Official(s) and/or principal investigator(s):
William J McCune, M.D., Principal Investigator, Affiliation: Professor of Internal Medicine

Overall contact:
William Joseph McCune, M.D., Phone: 734-936-5554, Email: jmccune@umich.edu

The purpose of this study it to determine whether the use of a gonadotropin releasing hormone (GnRH)-agonist (depot-leuprolide acetate) during cyclophosphamide (CYC) therapy in women with rheumatic diseases will provide greater ovarian protection than placebo.

Official title: GnRH-a for Ovarian Protection During CYC Therapy for Rheumatic Diseases

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: anti-mullerian hormone (AMH) measured as a continuous variable, specifically assessing the intra-person change from study entry (Day 0) to 6-month post-intervention visit

Secondary outcome: Proportion of patients with AMH of ≤1.0 ng/mL vs >1 ng/mL, presence of menses, presence of either an AMH level of >1 ng/mL OR antral follicle count of >4. Continuous measures include: antral follicle count (AFC), ovarian volume, and FSH.

Detailed description: Patients will be women ages 18-40 with either a severe rheumatic disease requiring cyclophosphamide or interstitial lung disease requiring cyclophosphamide to be administered either daily orally; monthly intravenously; or intravenously every 2 weeks for 6 doses. Because cyclophosphamide treatment may be required urgently for some indications, study entry may occur before either the first or second dose of cyclophosphamide for patients receiving cyclophosphamide intravenously.

Minimum age: 18 Years. Maximum age: 40 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

1. Female, post menarche, not menopausal

2. Ages 18-40 years inclusive at enrollment

3. Diagnosis consistent with one of the following:

1. SLE: at least four American College of Rheumatology (ACR) criteria for SLE

2. Systemic vasculitis: including severe Wegener's granulomatosis, microscopic or macroscopic polyatreritisnodosa, or Churg Strauss disease

3. Isolated vasculitis of the central nervous system

4. Scleroderma with severe interstitial lung disease

5. Severe interstitial lung disease

4. Patient is adjudged by their treating physician to require either 6 monthly boluses of CYC or 6 fortnightly doses of CYC (Euro lupus protocol), or at least 3 months of daily oral CYC therapy

5. A satisfactory plan for contraception consistent with cyclophosphamide administration (when appropriate: depot progestins, IUD, combination oral contraception and/or dual barrier contraception).

Exclusion Criteria:

1. Symptoms consistent with ovarian failure based on gynecologic evaluation and confirmatory laboratory testing

2. Prior unilateral or bilateral oophorectomy

3. Cervical intraepithelial neoplasia (CIN 2, or more severe), that has not been adequately evaluated or is not being adequately treated

4. Contraindications to use of GnRH-a (e. g., undiagnosed abnormal uterine bleeding)

5. Prior adverse or allergic reaction to GnRH-a

6. A history of severe psychiatric disorders, particularly severe depression that is currently not adequately treated

7. History of significant noncompliance with medical treatment

8. Patients with major risk factors for decreased bone mineral content such as chronic alcohol and/or tobacco use, strong family history of osteoporosis, or chronic use of drugs that can reduce bone mass such as anticonvulsants that have not already been addressed with appropriate measures to preserve bone mass.

9. Pregnant or breastfeeding

10. Significant thrombotic event requiring treatment that will not have received appropriate therapy for at least 4 weeks before initiation of study drug.

William Joseph McCune, M.D., Phone: 734-936-5554, Email: jmccune@umich.edu

University of Michigan, Ann Arbor, Michigan 48109, United States; Recruiting
W Joseph McCune, M.D., Phone: 734-936-5561, Email: jmccune@umich.edu
Courtney Graft, Phone: 734-936-5562, Email: ccgraft@med.umich.edu
Joseph McCune, MD, Principal Investigator

Duke Unversity, Durham, North Carolina 27710, United States; Active, not recruiting

The Ohio State University, Columbus, Ohio 43210, United States; Active, not recruiting

West Penn Allegheny Health System, Pittsburgh, Pennsylvania 15224, United States; Active, not recruiting

Starting date: May 2011
Last updated: February 29, 2012