Principal Investigator: Kathleen O'Neil, MD

Abstract:

For severe disease manifestations of childhood-onset SLE (cSLE) intravenous chemotherapy using cyclophosphamide is required, whose side effects include gonadotoxicity. The risk of female adolescents with cSLE to develop premature ovarian failure (POF) with cyclophosphamide is at 11%. No drugs have been approved to protect patients with cSLE from chemotherapy associated ovarian damage including ovarian failure (OF).

Central hypotheses to be tested:  Triptorelin is safe and may effectively prevent ovarian damage including OF of adolescent females with cSLE requiring cyclophosphamide.

Specific Aims:

1. To determine the dose of triptorelin (1mo preparation) that is sufficient to maintain complete ovarian suppression (COS) for 4 weeks.

2. To optimize the time interval between triptorelin injection and infusion of cyclophosphamide.

3. To evaluate the safety of triptorelin at different doses, when used in adolescent females with SLE.

4. To obtain preliminary evidence of the efficacy of triptorelin for preventing ovarian damage including POF.

Methods:  50 pubertal females with cSLE (Tanner>2; age<21 years) who are newly requiring cyclophosphamide, will be studied in a phase I/II randomized double-blinded placebo-controlled clinical trial over a 23-month period. Patients on 4 different triptorelin dosing regimens will be studied (n=40) and compared to placebo-treated subjects (n=10). Safety data, information on the amount of triptorelin and the time period required to induce COS for 28 days between intramuscular injections as well as preliminary efficacy to protect from cyclophosphamide-induced ovarian damage are obtained.  Safety evaluation will focus on cSLE disease course, effects of autoimmunity, bone mineral density and the neuropsychiatric system.  Ovarian function testing includes basal and stimulated gonadotropions, inhibin-B and ovarian ultrasound.

Expected results:  The results of this study will provide pivotal information on the use of triptorelin in this population, permitting Watson to request orphan-drug designation of triptorelin for ovarian protection in cSLE.

Participant Inclusion Criteria:

Participant Compensation:

Contact Information:

Kathleen O’Neil, MD  405/271-7086 or e-mail kathleen-oneil@ousc.edu