NCT00124514

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

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
31

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jun 2003

Longer than P75 for phase_2

Geographic Reach
2 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2003

Completed
2.2 years until next milestone

First Submitted

Initial submission to the registry

July 26, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 28, 2005

Completed
8.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2014

Completed
6.9 years until next milestone

Results Posted

Study results publicly available

January 5, 2021

Completed
Last Updated

January 5, 2021

Status Verified

December 1, 2020

Enrollment Period

10.8 years

First QC Date

July 26, 2005

Results QC Date

September 9, 2020

Last Update Submit

December 8, 2020

Conditions

Keywords

SLELupusOvarian damageMenopause

Outcome Measures

Primary Outcomes (1)

  • Dose of Triptorelin for Ovarian Suppression

    Dose escalation was initiated If COS was not maintained with the 1st dose of study drug. Subsequent doses were increased by 25% or at least 20μg/kg dose. This procedure of dose increases by 25% or at least 20μg/kg dose was repeated until COS was maintained. Absolute max dose 7.8mg. Triptorelin (T1-T4) groups were pooled for analysis.

    baseline to week 24

Secondary Outcomes (1)

  • Length of Time of Triptorelin Treatment to Achieve Ovarian Suppression

    baseline to week 24

Study Arms (5)

Triptorelin T1

EXPERIMENTAL

Triptorelin Pamoate 25 μg/kg body weight

Drug: Triptorelin pamoate

Triptorelin T2

EXPERIMENTAL

Triptorelin Pamoate 50 μg/kg body weight

Drug: Triptorelin Pamoate

Triptorelin T3

EXPERIMENTAL

Triptorelin Pamoate 75 μg/kg body weight T3

Drug: Triptorelin Pamoate

Triptorelin T4

EXPERIMENTAL

Triptorelin Pamoate 100 μg/kg body weight T4

Drug: Triptorelin Pamoate

Placebo

PLACEBO COMPARATOR

Normal Saline

Other: placebo

Interventions

IM injection given monthly

Also known as: Trelstar Depot
Triptorelin T1
placeboOTHER

placebo 0.9% normal saline IM injection

Also known as: placebo 0.9% normal saline
Placebo

Eligibility Criteria

Age9 Years - 21 Years
Sexfemale
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Morgan Stanley Children's Hospital of New York

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Columbus Children's Hospital

Columbus, Ohio, 43205, United States

Location

Children's Hospital of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

University of Sao Paulo

São Paulo, Brazil

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Triptorelin PamoateSaline Solution

Condition Hierarchy (Ancestors)

Connective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing HormonePituitary Hormone-Releasing HormonesHypothalamic HormonesPeptide HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsNeuropeptidesPeptidesAmino Acids, Peptides, and ProteinsOligopeptidesNerve Tissue ProteinsProteinsCrystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical Preparations

Results Point of Contact

Title
Hermine Brunner
Organization
cincinnatichildrens

Study Officials

  • Hermine I Brunner, M.D. M.Sc.

    Children's Hospital Medical Center, Cincinnati

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
DIAGNOSTIC
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

July 26, 2005

First Posted

July 28, 2005

Study Start

June 1, 2003

Primary Completion

March 1, 2014

Study Completion

March 1, 2014

Last Updated

January 5, 2021

Results First Posted

January 5, 2021

Record last verified: 2020-12

Locations