Trial of Early Aggressive Drug Therapy in Juvenile Idiopathic Arthritis - Full Text View

Sponsors and Collaborators:	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Amgen
Information provided by:	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ClinicalTrials.gov Identifier:	NCT00443430

Purpose

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	Intervention	Phase
Polyarticular Juvenile Idiopathic Arthritis Juvenile Idiopathic Arthritis Juvenile Rheumatoid Arthritis Extended Oligoarthritis Juvenile Idiopathic Arthritis	Drug: methotrexate Drug: methotrexate, etanercept, prednisolone	Phase IV

MedlinePlus related topics: Juvenile Rheumatoid Arthritis Rheumatoid Arthritis

Drug Information available for: Prednisolone Prednisolone acetate Depo-medrol Methotrexate Medrol veriderm Methylprednisolone Etanercept Prednisolone sodium phosphate Prednisolone Sodium Succinate Methylprednisolone Sodium Succinate Methylprednisolone hemisuccinate 6-Methylprednisolone

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Trial of Early Aggressive Therapy in Juvenile Idiopathic Arthritis (TREAT in JIA)

Further study details as provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):

Primary Outcome Measures:

Proportion of participants who attain inactive disease by 6 months [ Time Frame: 6 months after initiation of study intervention ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	86
Study Start Date:	May 2007
Estimated Study Completion Date:	September 2010
Estimated Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator 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
2: Experimental 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 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.

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.

Eligibility

Ages Eligible for Study:	2 Years to 17 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00443430

Contacts

Contact: Carol A. Wallace, MD	206-987-2057	carrainfo@stanford.edu
Contact: Daniel J. Lovell, MD, MPH	513-636-8071	carrainfo@stanford.edu

Locations

United States, California
University of California San Francisco Medical Center	Recruiting
San Francisco, California, United States, 94143
Contact: Diana Milojevic, MD 415-502-4940 carrainfo@stanford.edu
Principal Investigator: Diana Milojevic, MD
Rady Children's Hospital	Recruiting
San Diego, California, United States, 92123-4282
Contact: Ilona Szer, MD carrainfo@stanford.edu
Principal Investigator: Ilona Szer, MD
Stanford University Medical Center	Recruiting
Palo Alto, California, United States
Contact: Peter Chiraseveenuprapund carrainfo@standford.edu
Contact: Abirami Sivagnanasundaram carrainfo@standford.edu
Principal Investigator: Peter Chiraseveenuprapund, MD
United States, Indiana
James Whitcomb Riley Hospital for Children	Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Andrea Bamford 317-278-0266 abamford@iupui.edu
Principal Investigator: Suzanne Bowyer, MD
United States, Massachusetts
Children's Hospital of Boston	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Robert Sundel, MD carrainfo@stanford.edu
Principal Investigator: Robert Sundel, MD
United States, New Jersey
Hackensack University Medical Center	Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Yukiko Kimura, MD 201-996-5306 carrainfo@stanford.edu
Principal Investigator: Yuki Kimura, MD
United States, New York
Schneider Children's Hospital	Recruiting
New Hyde Park, New York, United States, 11040
Contact: Beth Gottlieb, MD carrainfo@stanford.edu
Principal Investigator: Beth Gottlieb, MD
Children's Hospital at Montefiore	Recruiting
Bronx, New York, United States, 10467
Contact: Norm Ilowite, MD 718-741-2456 nilowite@montefiore.org
Principal Investigator: Norm Ilowite, MD
United States, North Carolina
Duke University	Recruiting
Durham, North Carolina, United States, 27710
Contact: Laura Schanberg, MD carrainfo@stanford.edu
Principal Investigator: Laura Schanberg, MD
United States, Ohio
Children's Hospital of Columbus	Recruiting
Columbus, Ohio, United States, 43205
Contact: Gloria Higgins, PhD, MD 614-722-5525 carrainfo@stanford.edu
Principal Investigator: Gloria Higgins
Cleveland Clinic Foundation	Recruiting
Cleveland, Ohio, United States, 44195
Contact: Sonya Crook, RN crooks@ccf.org
Principal Investigator: Phil Hashkes, MD
Cincinnati Children's Hospital Medical Center	Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Daniel J. Lovell, MD, MPH 513-636-8071 carrainfo@stanford.edu
Contact: Hermine Brunner, MD carrainfo@stanford.edu
Principal Investigator: Hermine Brunner, MD
United States, Oklahoma
Oklahoma University Health Science Center	Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Kathleen O'Neil, MD carrainfo@stanford.edu
Principal Investigator: Kathleen O'Neil, MD
United States, Pennsylvania
Childrens Hospital Pittsburg	Recruiting
Pittsburg, Pennsylvania, United States
Contact: Margalit Rosenkranz carrainfo@stanford.edu
Contact: Judy Henry carrainfo@stanford.edu
Principal Investigator: Margalit Rosenkranz
United States, Texas
Texas Scottish Rite Hospital	Recruiting
Dallas, Texas, United States, 75219
Contact: Heather Benham, RN, CPNP Heather.Benham@tsrh.org
Principal Investigator: Lynn Punaro, MD
United States, Utah
University of Utah	Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Andrew Zeft, MD carrainfo@stanford.edu
Principal Investigator: Andrew Zeft, MD
United States, Washington
Seattle Children's Hospital and Regional Medical Center	Recruiting
Seattle, Washington, United States, 98105
Contact: Jennifer Wargula, MD 206-884-4558 carrainfo@stanford.edu
Contact: Stephanie Hamilton, BA, BSN 206-987-4558 stephanie.hamilton@seattlechildrens.org
Principal Investigator: Jennifer Wargula, MD

Sponsors and Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Amgen

Investigators

Principal Investigator:

Carol A. Wallace, MD

Childrens Hospital and Regional Medical Center

More Information

Additional Information:

Click here for the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Web site This link exits the ClinicalTrials.gov site

Publications:

Lovell DJ, Reiff A, Jones OY, Schneider R, Nocton J, Stein LD, Gedalia A, Ilowite NT, Wallace CA, Whitmore JB, White B, Giannini EH; Pediatric Rheumatology Collaborative Study Group. Long-term safety and efficacy of etanercept in children with polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum. 2006 Jun;54(6):1987-94.

Wallace CA. Current management of juvenile idiopathic arthritis. Best Pract Res Clin Rheumatol. 2006 Apr;20(2):279-300. Review.

Wallace CA, Ruperto N, Giannini E; Childhood Arthritis and Rheumatology Research Alliance; Pediatric Rheumatology International Trials Organization; Pediatric Rheumatology Collaborative Study Group. Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol. 2004 Nov;31(11):2290-4.

Responsible Party:	University of Washington Department of Pediatrics ( Carol Wallace, MD )
Study ID Numbers:	R01 AR049762, 1 R01 AR049762-01A2
Study First Received:	March 2, 2007
Last Updated:	April 8, 2009
ClinicalTrials.gov Identifier:	NCT00443430 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):

Childhood Arthritis
Juvenile Arthritis
Juvenile Arthritis Treatment
Childhood Arthritis Drug Treatment

Juvenile Arthritis Remission
Inactive Disease in Juvenile Arthritis
Childhood Polyarthritis
Extended Oligoarthritis

Study placed in the following topic categories:

Antimetabolites
Anti-Inflammatory Agents
Immunologic Factors
Methylprednisolone
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Arthritis, Rheumatoid
Antiemetics
Prednisolone acetate
TNFR-Fc fusion protein
Neuroprotective Agents
Hormones
Musculoskeletal Diseases
Arthritis
Connective Tissue Diseases

Methotrexate
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Aggression
Methylprednisolone Hemisuccinate
Autoimmune Diseases
Arthritis, Juvenile Rheumatoid
Antineoplastic Agents, Hormonal
Joint Diseases
Methylprednisolone acetate
Rheumatic Diseases
Folic Acid Antagonists
Immunosuppressive Agents
Glucocorticoids
Polyarthritis

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Methylprednisolone
Physiological Effects of Drugs
Arthritis, Rheumatoid
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
TNFR-Fc fusion protein
Hormones
Therapeutic Uses
Abortifacient Agents
Methotrexate
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors

Methylprednisolone Hemisuccinate
Arthritis, Juvenile Rheumatoid
Immune System Diseases
Antineoplastic Agents, Hormonal
Abortifacient Agents, Nonsteroidal
Glucocorticoids
Antimetabolites
Immunologic Factors
Antineoplastic Agents
Prednisolone acetate
Reproductive Control Agents
Neuroprotective Agents
Musculoskeletal Diseases
Sensory System Agents
Arthritis

ClinicalTrials.gov processed this record on May 07, 2009