Clinical trial NCT00124514: Triptorelin for Ovary Protection in Childhood Onset Lupus
Official title: Triptorelin for Ovary Protection in Childhood Onset Lupus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Keywords: SLE
Lupus
Ovarian damage
Menopause
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Watson Pharmaceuticals
First posted: 2005-07-28
Enrollment: 31
Sex: FEMALE
Minimum age (years): 9
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The purpose of this study is to test the safety of triptorelin when used for the protection of the ovaries (pair of female reproductive organs) during cyclophosphamide therapy for systemic lupus erythematosus (SLE; lupus) and to see what effects (good or bad) it has on patients. The study will be done with female patients who have been diagnosed with systemic lupus erythematosus, are younger than 21 years of age, and require intravenous cyclophosphamide to control the disease. Each patient will be in the study for approximately 23 months, until 4 months after the intravenous cyclophosphamide treatment has been completed.

This study is currently being conducted at 3 sites across the United States and Brazil (Los Angeles, Cincinnati and San Paulo Brazil). A total of 50 patients will participate in this study.

Each patient will be randomized (assigned) to one of 5 groups. Randomization means that patients are put into a group completely by chance. It is like flipping a coin. Neither the patient nor the study staff knows what group the patient is in. The patient has a 20% chance of being placed in any group.

This is a dose escalation study, each patient will receive the first dose of the study drug (T1 - T4, placebo). If a patient has complete ovarian suppression on day 27 after the initial injection of study drug, then she will remain on this weight-adjusted dose of study drug throughout the study. The dose will be increased up for a weight gain of 5kg or greater. The dose will not be adjusted downward for a weight loss. If COS was not maintained with the 1st dose of study drug, then the subsequently injected 2nd dose will be increased by 25% or at least 20 microgram/kg/dose. The maximal dose of 150 microgram/kg/dose will not be exceeded. The absolute maximum dose is 20 mg.

Funding Source: FDA OOPD and Watson Pharmaceuticals

Detailed description: Lupus is an autoimmune disease that may harm all organs in the body and especially affects the kidney, brain, skin and lungs. Cyclophosphamide is a very effective medication to treat lupus, but it can damage the ovaries (pair of reproductive organs).

Only female lupus patients may participate in this study.

Eligibility criteria: Inclusion Criteria:

* Females under the age of 21 and non-pregnant
* Tanner stage of 2 or above as determined by physical examination of breast stage
* Diagnosis with SLE using the updated American College of Rheumatology (ACR) Classification Criteria for SLE 1
* Severe SLE requiring cyclophosphamide therapy
* Bone mineral density z-score \> - 2.0
* Must be using a medically acceptable form of birth control during the study and must not be pregnant at the screening visit
* No clinically significant abnormal findings other than those consistent with the diagnosis of childhood-onset SLE (cSLE) on the physical examination, medical history or clinical laboratory results during screening
* Currently on any combination of medication but must not have been treated with more than one dose of cyclophosphamide or other gonadotoxic medications in the past
* Voluntary consent or, if under the age of consent, assent to participate in this study with permission by a legal guardian

Exclusion Criteria:

* Male patients of any age
* Female patients with a Tanner stage of 1
* Positive blood pregnancy test at screening or taking oral or injectable birth-control medications
* Prior exposure to more than one dose of gonadotoxic medications including cyclophosphamide
* History of allergic or adverse response to triptorelin
* Diagnosed with hypogonadism prior to cyclophosphamide exposure
* Acutely life-threatening disease activity that prohibits inclusion in a clinical trial
* History of clinically significant gastrointestinal tract, renal, hepatic, endocrine, oncologic, pulmonary (asthma accepted), or cardiovascular disease; or a history of tuberculosis, epilepsy, diabetes, depression, psychosis, or any other non-cSLE condition, which in the opinion of the physician, would jeopardize the safety of the subject or impact the validity of the study results
* Patient age 18 years of younger with severe depression as defined by a CDI (Children's Depression Inventory) score of \> 23 or a patient age 19 to 21 years with severe depression as defined by a BDI (Beck's Depression Inventory) score \> 29
* Patient admits to suicidal thoughts at screening visit
* Bone mineral density lower than z = -2.0.

Primary outcomes:
measure: Dose of Triptorelin for Ovarian Suppression
timeFrame: baseline to week 24
Secondary outcomes:
measure: Length of Time of Triptorelin Treatment to Achieve Ovarian Suppression
timeFrame: baseline to week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Morgan Stanley Children's Hospital of New York
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Columbus Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Children's Hospital of Oklahoma
state: Oklahoma
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: São Paulo
country: Brazil
facility: University of Sao Paulo
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Hermine I Brunner, M.D. M.Sc.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brunner HI, Silva CA, Reiff A, Higgins GC, Imundo L, Williams CB, Wallace CA, Aikawa NE, Nelson S, Klein-Gitelman MS, Rose SR. Randomized, double-blind, dose-escalation trial of triptorelin for ovary protection in childhood-onset systemic lupus erythematosus. Arthritis Rheumatol. 2015 May;67(5):1377-85. doi: 10.1002/art.39024.