Triptorelin for Ovary Protection in Childhood Onset Lupus

NCT ID: NCT00124514

Last Updated: 2021-01-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2014-03-31

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.

Conditions

Systemic Lupus Erythematosus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: TRIPLE

Study Groups

Triptorelin T1

Triptorelin Pamoate 25 μg/kg body weight

Group Type: EXPERIMENTAL

Triptorelin pamoate

Intervention Type: DRUG

IM injection given monthly

Triptorelin T2

Triptorelin Pamoate 50 μg/kg body weight

Group Type: EXPERIMENTAL

Triptorelin Pamoate

Intervention Type: DRUG

IM injection given monthly

Triptorelin T3

Triptorelin Pamoate 75 μg/kg body weight T3

Group Type: EXPERIMENTAL

Triptorelin Pamoate

Intervention Type: DRUG

IM injection given monthly

Triptorelin T4

Triptorelin Pamoate 100 μg/kg body weight T4

Group Type: EXPERIMENTAL

Triptorelin Pamoate

Intervention Type: DRUG

IM injection given monthly

Placebo

Normal Saline

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

placebo 0.9% normal saline IM injection

Interventions

Triptorelin pamoate

IM injection given monthly

Intervention Type: DRUG

Triptorelin Pamoate

IM injection given monthly

Intervention Type: DRUG

Triptorelin Pamoate

IM injection given monthly

Intervention Type: DRUG

Triptorelin Pamoate

IM injection given monthly

Intervention Type: DRUG

placebo

placebo 0.9% normal saline IM injection

Intervention Type: OTHER

Other Intervention Names

Trelstar Depot; Trelstar Depot; Trelstar Depot; Trelstar Depot; placebo 0.9% normal saline

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.

• Minimum Eligible Age: 9 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Watson Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Hermine Brunner, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hermine I Brunner, M.D. M.Sc.

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Locations

Children's Hospital of Los Angeles

Los Angeles, California, United States

Children's Memorial Hospital

Chicago, Illinois, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Morgan Stanley Children's Hospital of New York

New York, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Columbus Children's Hospital

Columbus, Ohio, United States

Children's Hospital of Oklahoma

Oklahoma City, Oklahoma, United States

Seattle Children's Hospital

Seattle, Washington, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

University of Sao Paulo

São Paulo, , Brazil

Countries

United States; Brazil

References

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.

Reference Type: DERIVED

PMID: 25676588 (View on PubMed)

Other Identifiers

FD-R-00239

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2008-1045

Identifier Type: -

Identifier Source: org_study_id

NCT00088244

Identifier Type: -

Identifier Source: nct_alias