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Understanding the Pathogenesis and Treatment of Childhood Onset Dermatomyositis

Primary Purpose

Dermatomyositis

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Prednisone
Methotrexate
Etanercept
Sponsored by
Children's Hospital Medical Center, Cincinnati
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dermatomyositis focused on measuring Juvenile Dermatomyositis, Pediatric, Randomized Clinical Trial, Pediatric Rheumatology

Eligibility Criteria

4 Years - 16 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion criteria at the time of enrollment: Definite or probable diagnosis of JDMS by the criteria of Bohan and Peter No prior systemic steroid treatment for JDMS If able to become pregnant (females) or impregnate (males) and are sexually active, then must have negative serum pregnancy test at baseline and be utilizing effective form of birth control Patient and/or parent or legal guardian must be willing to sign consent and assent forms Exclusion criteria at the time of enrollment: History of chronic or recurrent infections sufficient to preclude the use of etanercept Prior treatment with specific TNF-blocking agents Demonstration of cutaneous or gastrointestinal (GI) ulceration at the time of diagnosis JDMS-related pulmonary disease at time of diagnosis (interstitial lung disease or aspiration pneumonia confirmed by radiograph) JDMS-related cardiomyopathy (echocardiogram confirmation) Any uncontrolled, clinically significant pre-existent systemic disease (hepatic, renal, neurological, endocrine, cardiac, gastrointestinal, or hematologic disease) within 24 weeks of start of study Known HIV, hepatitis B surface antigen not related to vaccination, or hepatitis C antibody positivity Pregnant or nursing female Any of the following laboratory abnormalities at baseline: platelet count < 100,000/cmm, total white cell count of < 3000 cells/cmm, neutrophils < 1000 cells/cmm, serum bilirubin > 2 times upper limit of normal, estimated creatinine clearance of < 90 mL/min/1.73 M2 BSA estimated by formula for males age 2 to <13 (0.55 X ht in cms/serum creatinine), age 13-18 (0.7 X ht in cms/serum creatinine) and females age 2-18 (0.55 X ht in cms/serum creatinine) Received live virus vaccination within 3 months prior to study entry (contraindication for MTX or etanercept therapy) Past or current substance abuse or psychiatric history that would interfere with ability to give informed consent or comply with study requirements or physician instructions

Sites / Locations

  • Cincinnati Childrens Hospital Medical Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
May 7, 2002
Last Updated
July 31, 2013
Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Immunex Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00035958
Brief Title
Understanding the Pathogenesis and Treatment of Childhood Onset Dermatomyositis
Official Title
Toward Improved Understanding of Pathogenesis and Treatment of Childhood Onset Dermatomyositis
Study Type
Interventional

2. Study Status

Record Verification Date
July 2013
Overall Recruitment Status
Terminated
Why Stopped
Incorporating the recommendations of the NIH-formed DSMB in the study procedures would make the project budget over the limit for this funding mechanism.
Study Start Date
August 2002 (undefined)
Primary Completion Date
August 2002 (Actual)
Study Completion Date
August 2002 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Immunex Corporation

4. Oversight

5. Study Description

Brief Summary
Juvenile dermatomyositis (JDMS) is one of the most serious of the childhood rheumatic diseases. The theory behind this trial is that early introduction of etanercept or methotrexate will prove to be effective in the treatment of JDMS. Pretreatment muscle biopsies, we believe there will be abnormalities in the blood vessels that will be correlated with worse physical strength and daily functional ability. The long-term goal is to improve the treatment of this serious childhood onset rheumatic disease and to better understand the pathogenic mechanism for the development of the vasculopathy (disorder of blood vessels) of JDMS. Identification of the specific mechanism of the vasculopathy may allow for the rational introduction of biologic treatments focused on vascular growth.
Detailed Description
The mortality of JDMS is 3-39% with over 40% of patients demonstrating long-term disability. Current first line therapy is high-dose corticosteroids with the attendant significant drug-related toxicity. Over 30% of JDMS patients fail to respond adequately to steroids and require additional immunosuppression, none of which have been tested in prospective, randomized, controlled trials. The unique occlusive vasculopathy in JDMS is critical in the pathogenesis and predictive of prognosis but poorly understood. Elevated levels of tumor necrosis factor (TNF) alpha have been shown to be present in JDMS and are associated with a more severe and chronic course. Seventy-five children with definite JDMS will be enrolled in a 24-month prospective, randomized, multicentered trial comparing 3 treatments: oral prednisone (P), combination of oral prednisone and methotrexate (P/MTX), and combination of oral prednisone and etanercept (P/E). Primary response measures will be muscle strength and mean duration of steroid therapy. Secondary response variables are disability in daily function and height and weight growth velocity (steroid toxicity measures). The combination of P/E will be tested and compared to both P alone and the combination of P/MTX after 3, 6, 12, 18, and 24 months of treatment. In addition, the combination of P/MTX will be compared to P alone after 3, 6, 12, 18, and 24 months of treatment. In pretreatment muscle biopsies, proangiogenic factors (such as vascular endothelial cell growth factor and basic fibroblast growth factor), angiostatic factors (such as angiostatin and endostatin), and vascular morphology (vessel number, width, length and area) will be quantified and tested for ability to predict muscle strength and functional ability 3, 6, 12, 18, and 24 months later.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dermatomyositis
Keywords
Juvenile Dermatomyositis, Pediatric, Randomized Clinical Trial, Pediatric Rheumatology

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
75 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Type
Drug
Intervention Name(s)
Etanercept

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria at the time of enrollment: Definite or probable diagnosis of JDMS by the criteria of Bohan and Peter No prior systemic steroid treatment for JDMS If able to become pregnant (females) or impregnate (males) and are sexually active, then must have negative serum pregnancy test at baseline and be utilizing effective form of birth control Patient and/or parent or legal guardian must be willing to sign consent and assent forms Exclusion criteria at the time of enrollment: History of chronic or recurrent infections sufficient to preclude the use of etanercept Prior treatment with specific TNF-blocking agents Demonstration of cutaneous or gastrointestinal (GI) ulceration at the time of diagnosis JDMS-related pulmonary disease at time of diagnosis (interstitial lung disease or aspiration pneumonia confirmed by radiograph) JDMS-related cardiomyopathy (echocardiogram confirmation) Any uncontrolled, clinically significant pre-existent systemic disease (hepatic, renal, neurological, endocrine, cardiac, gastrointestinal, or hematologic disease) within 24 weeks of start of study Known HIV, hepatitis B surface antigen not related to vaccination, or hepatitis C antibody positivity Pregnant or nursing female Any of the following laboratory abnormalities at baseline: platelet count < 100,000/cmm, total white cell count of < 3000 cells/cmm, neutrophils < 1000 cells/cmm, serum bilirubin > 2 times upper limit of normal, estimated creatinine clearance of < 90 mL/min/1.73 M2 BSA estimated by formula for males age 2 to <13 (0.55 X ht in cms/serum creatinine), age 13-18 (0.7 X ht in cms/serum creatinine) and females age 2-18 (0.55 X ht in cms/serum creatinine) Received live virus vaccination within 3 months prior to study entry (contraindication for MTX or etanercept therapy) Past or current substance abuse or psychiatric history that would interfere with ability to give informed consent or comply with study requirements or physician instructions
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel J. Lovell, MD, MPH
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Childrens Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Understanding the Pathogenesis and Treatment of Childhood Onset Dermatomyositis

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