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Trial of Early Aggressive Drug Therapy in Juvenile Idiopathic Arthritis

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.
ClinicalTrials.gov Identifier: NCT00443430
Recruitment Status : Completed
First Posted : March 6, 2007
Results First Posted : May 31, 2013
Last Update Posted : May 31, 2013
Information provided by (Responsible Party):

Study Description
Brief Summary:
The purpose of this study is to compare two aggressive drug regimens for children with poly-juvenile idiopathic arthritis (JIA) and extended oligo JIA.

Condition or disease Intervention/treatment Phase
Juvenile Chronic Polyarthritis Juvenile Idiopathic Arthritis Juvenile Rheumatoid Arthritis Drug: methotrexate Drug: methotrexate - etanercept - prednisolone arm Phase 4

Detailed Description:

JIA is a type of arthritis with no definite cause and an onset prior to 16 years of age. JIA causes joint destruction, pain, and permanent disability. There are multiple types of JIA; collectively, they represent one of the most common chronic diseases in children and the most prevalent pediatric rheumatic illness. Poly-JIA, one type of JIA, affects at least five joints in the body within the first 6 months of disease. Long-term remission of poly-JIA is uncommon, and most children must remain on multiple combinations of medications for many years. The usual treatment for poly-JIA is based upon the gradual addition of medications that might be more effective in treating this disease. There is a need to find uniformly effective treatments for children with poly-JIA. Based on previous adult arthritis studies, there appears to be an early window of opportunity in the disease progression during which aggressive therapy has a profound beneficial long-term effect. The purpose of this study is to compare the effectiveness of two aggressive drug regimens in treating children with poly-JIA. Specifically, the study will determine whether aggressive therapy started in the first 6 months of disease onset can result in inactive disease and clinical remission while on these medications.

All participants will receive weekly methotrexate shots while in the study. In addition, participants will be randomly assigned to one of two groups:

  • Group 1 participants will receive placebo etanercept shots for up to 12 months and daily placebo prednisolone liquid for 4 months.
  • Group 2 participants will receive etanercept shots for up to 12 months and daily prednisolone liquid for 4 months.

The study will last up to 12 months and include two parts. Part A will last 1 to 6 months, depending on response to assigned treatments. If participants are still experiencing active arthritis at 6 months, they will be offered open-label treatment with etanercept and prednisolone. If participants experience inactive disease any time prior to 6 months, they will enter Part B of the study. During Part B, which will last up to 6 months, participants will remain on the same treatment regimen that they were provided in Part A. If participants experience inactive disease followed by a flare of disease any time during the study, they will stop participating.

During the study, there will be 11 study visits for all participants. Study visits will include a physical exam, including joint evaluations; blood and urine collection; and questionnaires regarding function, quality of life, medication compliance, other medications used, infections, and adverse symptoms.

Blood will be collected for translational studies.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 85 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Trial of Early Aggressive Therapy in Juvenile Idiopathic Arthritis (TREAT in JIA)
Study Start Date : May 2007
Primary Completion Date : October 2010
Study Completion Date : October 2010

Arms and Interventions

Arm Intervention/treatment
Active Comparator: Methotrexate Arm
Methotrexate 0.5 mg/kg given by subcutaneous injection once per week, plus placebo etanercept and placebo prednisolone
Drug: methotrexate
Methotrexate 0.5 mg/kg given by sub cutaneous injection once per week, plus placebo etanercept and and placebo prednisolone
Other Names:
  • placebo enbrel
  • placebo prednisolone
Active Comparator: Methotrexate-Etanercept-Prednisolone Arm
Methotrexate 0.5 mg/kg given by subcutaneous injection once per week, plus etanercept 0.8 mg/kg given by subcutaneous injection once per week, plus prednisolone by mouth daily with decreasing dose tapered over 16 weeks
Drug: methotrexate - etanercept - prednisolone arm
methotrexate 0.5 mg/kg given by sub cutaneous injection once per week, plus etanercept 0.8 mg/kg given by sub cutaneous injection once per week, plus prednisolone, by mouth daily with decreasing dose tapered over 16 weeks.
Other Names:
  • enbrel
  • prednisone

Outcome Measures

Primary Outcome Measures :
  1. Proportion of Participants Who Attain Inactive Disease by 6 Months [ Time Frame: 6 months after initiation of study intervention ]

Secondary Outcome Measures :
  1. Safety Profiles, Including the Number of Treatment-emergent, Serious, or Unexpected Adverse Events and Other Important Medical Events [ Time Frame: Over 12 months maximum study participation per subject ]
  2. Clinical Remission on Medication [ Time Frame: 12 months or end of study ]
    6 months of clinical inactive disease

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of active poly-JIA as determined by International League of Associations for Rheumatology (ILAR) criteria
  • Onset of signs and symptoms of poly-JIA for 12 months or less prior to study screening
  • Willing to use acceptable forms of contraception for the duration of the study and for 3 months after the study
  • Parent or guardian willing to provide informed consent
  • Able to attend all study visits

Exclusion Criteria:

  • Received or currently receiving disease-modifying antirheumatic drugs (DMARDs), biologic, or prednisone for any duration for treatment of poly-JIA, with the following exceptions:

    1. Methotrexate duration must be less than or equal to 6 weeks at a dose of less than or equal to 0.5 mg/kg/week (40 mg max),
    2. Steroid use has been less than or equal to 4 weeks and the subject is off of steroids for at least 1 week prior to enrollment
  • Received intramuscular or soft-tissue injections of corticosteroids for treatment of poly-JIA before receiving the first dose of study medication. Up to 2 joint injections with intra-articular steroids (IAS) will be allowed up to 7 days after the baseline visit.
  • History of or active cancer of any type
  • Active gastrointestinal disease (e.g., inflammatory bowel disease)
  • Chronic or acute kidney or liver disorder
  • Significant blood clotting defect
  • AST (SGOT), ALT (SGPT), or BUN levels more than two times the upper level of normal, creatinine levels more than 1.5 mg/dl, or any other laboratory abnormality considered to be clinically significant within 28 days prior to baseline
  • Chronic condition (e.g., diabetes, epilepsy) that is either not stable or poorly controlled and may interfere with study participation
  • Received any investigational medication within 30 days prior to the first dose of study medication or scheduled to receive an investigational drug (other than the study medications) during the course of the study
  • Chronic or active infection or any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 30 days prior to study screening
  • HIV infected
  • Known past or current hepatitis infection
  • Received a live virus vaccine within 1 month prior to baseline
  • Purified protein derivative (PPD) positive (positive tuberculosis [TB] test)
  • Pregnancy
  • Any medical condition that would make study participation difficult or inadvisable in the opinion of the investigator
  • History of or current psychiatric illness that would interfere with study participation
  • History of alcohol or drug abuse within the 6 months prior to study entry that would interfere with study participation
  • Inability to comply with study requirements for any reason
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): NCT00443430

United States, California
Stanford University Medical Center
Palo Alto, California, United States, 94305
Rady Children's Hospital
San Diego, California, United States, 92123-4282
University of California San Francisco Medical Center
San Francisco, California, United States, 94143
United States, Massachusetts
Children's Hospital of Boston
Boston, Massachusetts, United States, 02115
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Children's Hospital at Montefiore
Bronx, New York, United States, 10467
Schneider Children's Hospital
New Hyde Park, New York, United States, 11040
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Children's Hospital of Columbus
Columbus, Ohio, United States, 43205
United States, Oklahoma
Oklahoma University Health Science Center
Oklahoma City, Oklahoma, United States, 73104
United States, Texas
Texas Scottish Rite Hospital
Dallas, Texas, United States, 75219
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Washington
Seattle Children's Hospital and Regional Medical Center
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Seattle Children's Hospital
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Principal Investigator: Carol A. Wallace, MD Childrens Hospital and Regional Medical Center
More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Carol Wallace, Principal Investigator, Seattle Children's Hospital
ClinicalTrials.gov Identifier: NCT00443430     History of Changes
Other Study ID Numbers: R01AR049762 ( U.S. NIH Grant/Contract )
5R01AR049762-02 ( U.S. NIH Grant/Contract )
First Posted: March 6, 2007    Key Record Dates
Results First Posted: May 31, 2013
Last Update Posted: May 31, 2013
Last Verified: May 2013

Keywords provided by Carol Wallace, Seattle Children's Hospital:
Childhood Arthritis
Juvenile Arthritis
Juvenile Arthritis Treatment
Childhood Arthritis Drug Treatment
Juvenile Arthritis Remission
Inactive Disease in Juvenile Arthritis
Childhood Polyarthritis
Extended Oligoarthritis

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Arthritis, Juvenile
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methylprednisolone Hemisuccinate
Prednisolone acetate
Methylprednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents