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GnRH-a for Ovarian Protection During CYC Therapy for Rheumatic Diseases (LUPRON)

This study has been terminated.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01257802
First Posted: December 10, 2010
Last Update Posted: June 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Joseph Mccune, University of Michigan
  Purpose
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.

Condition Intervention Phase
Lupus Erythematosus, Systemic Systemic Vasculitis Isolated Angiitis of Central Nervous System Lung Disease With Systemic Sclerosis Lung Disease Interstitial Diffuse Drug: depot leuprolide acetate 3.75 mg Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: GnRH-a for Ovarian Protection During CYC Therapy for Rheumatic Diseases

Resource links provided by NLM:


Further study details as provided by Joseph Mccune, University of Michigan:

Primary Outcome Measures:
  • 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 [ Time Frame: Day 0 to 6-month post-intervention visit ]
    AMH was quantified in vitro a commercially available enzyme linked immunosorbent assay (ELISA) (Beckman Coulter; Marseille, France) was used for in vitro quantitative measurement of serum AMH.


Secondary Outcome Measures:
  • Count of Patients With AMH of ≤1.0 ng/mL vs >1 ng/mL, [ Time Frame: baseline and 6 months ]
    AMH level ≤1.0 predicts onset of menopause within 5 years in normal women

  • Number of Participants With Either an AMH Level of >1 ng/mL OR Antral Follicle Count of >4. [ Time Frame: baseline and 6 months ]
    An AMH level of >1 ng/ml and/or an antral follicle count of >4 in either ovary is a strong predictor of residual ovarian function

  • Mean Antral Follicle Count (AFC) [ Time Frame: baseline and 6 months ]
    Mean antral follicle count (AFC) is the average number of follicles counted in each of 2 ovaries

  • Mean Ovarian Volume. [ Time Frame: baseline and 6 months ]
    Mean ovarian volume reflects the preservation of ovarian tissue despite exposure to cyclophosphamide; reduced ovarian size is documented in cyclophosphamide treated patients


Enrollment: 14
Study Start Date: May 2011
Study Completion Date: November 2015
Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: LUPRON
Monthly depot leuprolide acetate 3.75 mg injection during cyclophosphamide administration. First dose of study drug given at least 10 days before following dose of cyclophosphamide if cyclophosphamide is given in biweekly or monthly boluses
Drug: depot leuprolide acetate 3.75 mg
Monthly depot leuprolide acetate 3.75 mg vs placebo during cyclophosphamide administration. First dose of study drug given at least 10 days before following dose of cyclophosphamide if cyclophosphamide is given in biweekly or monthly boluses
Other Name: LUPRON depot 3.75 mg
Placebo Comparator: Placebo
Monthly placebo injection during cyclophosphamide administration. First dose of study drug given at least 10 days before following dose of cyclophosphamide if cyclophosphamide is given in biweekly or monthly boluses.
Drug: Placebo
Monthly placebo during cyclophosphamide administration. First dose of study drug given at least 10 days before following dose of cyclophosphamide if cyclophosphamide is given in biweekly or monthly boluses

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.

Of 16 participants who were screened, only 14 were randomized and only 7 participants actually completed the study. Due to this low number, follicle stimulating hormone (FSH) levels were not obtained.

Secondary outcome measures that are not available include presence of menses and FSH.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria
  1. Female, post menarche, not menopausal
  2. Ages 18-40 years inclusive at enrollment
  3. Diagnosis consistent with a rheumatic or autoimmune disease requiring 3-6 months of daily or intermittent cyclophosphamide therapy. This may include, but is not limited to:

    • Systemic lupus
    • Sjogren's syndrome
    • Systemic vasculitis
    • Isolated vasculitis of the central nervous system
    • Other autoimmune neurologic diseases requiring cyclophosphamide including transverse myelitis, peripheral neuropathies, multiple sclerosis, neuromyelitis optica, and retinal vasculitis
    • Behcet's syndrome
    • Scleroderma
    • Inflammatory myositis
    • Interstitial lung disease, other autoimmune pulmonary diseases requiring cyclophosphamide
    • Overlap connective tissue diseases not precisely fitting the above definitions clearly requiring cyclophosphamide for severe immune mediated organ damage
    • Rheumatoid vasculitis
  4. Patients will have planned cyclophosphamide treatment according to any one of the following regimens:

    • 3 to 6 months of daily oral cyclophosphamide: Lupron/placebo must be given within four (4) weeks of initiation of daily cyclophosphamide.
    • The Eurolupus regimen consisting of 6 fortnightly biweekly boluses of 500 mg cyclophosphamide: First dose of Lupron/placebo must be given 10 days prior to the second dose of cyclophosphamide
    • 3 to 6 monthly boluses of cyclophosphamide by the NIH regimen: First dose of Lupron/placebo must be given 10 days prior to the second dose of cyclophosphamide
  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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01257802


Locations
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Joseph Mccune
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: William J McCune, M.D. Professor of Internal Medicine
  More Information

Responsible Party: Joseph Mccune, Michael H. and Marcia S. Klein Professor of Rheumatic Diseases and Director, Lupus Clinic, University of Michigan
ClinicalTrials.gov Identifier: NCT01257802     History of Changes
Other Study ID Numbers: HUM00043071
5R01HD066139 ( U.S. NIH Grant/Contract )
First Submitted: December 9, 2010
First Posted: December 10, 2010
Results First Submitted: April 14, 2017
Results First Posted: June 27, 2017
Last Update Posted: June 27, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Fertility Agents, Female
Lung Diseases
Vasculitis
Rheumatic Diseases
Collagen Diseases
Lupus Erythematosus, Systemic
Systemic Vasculitis
Lung Diseases, Interstitial
Sclerosis
Respiratory Tract Diseases
Connective Tissue Diseases
Skin Diseases
Vascular Diseases
Cardiovascular Diseases
Musculoskeletal Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Cyclophosphamide
Leuprolide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents


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