Study of Cytokines in Children With Opsoclonus-Myoclonus Syndrome

Completed

• Conditions: Opsoclonus-myoclonus Syndrome

• Registration Number: NCT00806182
• Lead Sponsor: National Pediatric Neuroinflammation Organization, Inc.

Brief Summary

The purpose of this study is to determine if cytokines, inflammatory mediators, are increased in spinal fluid and blood, correlate with disease activity, and could serve as biomarkers or therapeutic targets in children with opsoclonus-myoclonus syndrome (OMS), an autoimmune complication of the tumor neuroblastoma.

Detailed Description

In this translational research, immunological mechanisms that underlie the assault of the immune system on the brain in paraneoplastic opsoclonus-myoclonus syndrome (OMS) are under evaluation. To test our principal hypothesis that there is an imbalance of pro-inflammatory (Th1) and anti-inflammatory (Th2) cytokines in OMS, a comprehensive cytokine panel will be measured by enzyme-linked immunosorbent assay (ELISA) and multiplexed fluorescent bead-based immunoassay detection (LUMINEX 100 Lab MAP system)in blood and cerebrospinal fluid (CSF) of 400 children. To test the second hypothesis that cytokines could serve as biomarkers of disease activity in OMS, cytokine concentrations will be correlated with clinical variables, such as disease severity, OMS duration, prior relapses, and remissions, as well as immunological variables, such as lymphocyte subset analysis. The cytokine 'biomarker profile' could aid decision making for early intervention by identifying children at high risk for relapse and poor outcome and allow targeting of the most implicated inflammatory cytokines by cytokine therapies. To test our third hypothesis that lack of response to immunotherapy is due in part to failure to increase the expression of anti-inflammatory Th2 cytokines, we will make paired pre/post comparisons of the impact of immunotherapies given in the course of clinical care \[steroids, adrenocorticotropin (ACTH), intravenous immunoglobulins (IVIg), rituximab, chemotherapy, other drugs, combinations\] on the cytokine and clinical profile. This research could lead to the application of commercially-available cytokines and cytokine blockers or to the development of new ones for OMS.

Study Timeline

• Study Start: 2008-01
• Study First Submitted: 2008-12-08
• Study First Submitted QC: 2008-12-09
• Study First Posted: 2008-12-10
• Primary Completion: 2016-12
• Study Completion: 2016-12
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-19
• Last Update Posted: 2017-05-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

• Clinical diagnosis of OMS

Exclusion Criteria

• Equivocal diagnosis
• Contraindications to lumbar puncture
• Treatment with agents outside the scope of the study

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Reduction in inflammatory cytokines	6 and 12 months	Reduction in the concentration of inflammatory chemokines/cytokines between clinical time points

Secondary Outcome Measures

Name	Time	Method
Correlation of cytokine concentration and clinical severity score.	6 and 12 months	Statistical correlation of chemokine/cytokine concentration with OMS motor severity as measured using the OMS video evaluation scale

Trial Locations

Locations (1)

National Pediatric Myoclonus Center, Formerly at Dept. of Neurology, Southern Illinois University School of Medicine; 🇺🇸 Springfield, Illinois, United States