Assessment of Lesion Activity Analysis in the Avonex- Steroid Azathioprine (ASA) Study

Completed

• Conditions: Multiple Sclerosis, Relapsing-remitting
• Interventions: Device: MRI

• Registration Number: NCT01628315
• Lead Sponsor: University at Buffalo

Brief Summary

* To examine short- and long-term value of appearance of new active lesions in predicting extent of cortical and subcortical deep gray matter (SDGM) atrophy over 5 years in ASA (Avonex- Steroid-Azathioprine)study.

* To explore how accumulation of cortical and SDGM atrophy over 5 years differs with respect to the number of new active lesions or amount of disease activity, in early relapsing-remitting multiple sclerosis (RRMS) patients who did or did not develop sustained disability progression.

* To examine the relationship between development of cortical and SDGM atrophy and regional likelihood of development of new active lesions over 5 years.

Detailed Description

Historically, MS has been classified as a disease predominantly affecting the white matter (WM) of the central nervous system. However, pathological changes in gray matter (GM) are increasingly recognized as an important component of the MS disease process. Advances in MRI have enabled detection of changes in GM morphology.

The ASA study was a placebo-controlled trial that evaluated efficacy of Avonex® alone and in combination with azathioprine (AZA) or AZA and corticosteroids as initial MS therapy in 181 patients with early RRMS over 5 years. The study was conducted in the Czech Republic, and all clinical and MRI examinations were concluded at 5 years.

No study has evaluated the evolution of cortical and SDGM atrophy in relation to global or regional accumulation of active lesions and/or occurrence of relapses both from predictive short- and long-term perspective. The ASA study provides a unique opportunity to prospectively study the impact of cortical and SDGM atrophy accumulation on long-term disability progression in a defined cohort of early RRMS patients who presented with various amount of disease activity, as measured by the appearance of new active lesions and occurrence of relapses.

By assessing lesion activity in the 0-6 and 6-12 months in the ASA study we will be able to evaluate predictive value for development of cortical and SDGM atrophy in early RRMS patients over 5 years with respect to the number of new active lesions or amount of disease activity in the first year. We will also evaluate lesion development from 12-60 months in relation to development of cortical and SDGM atrophy. We will also analyze accumulation of cortical and SDGM atrophy in early RRMS patients who will or will not develop sustained disability progression, based on the number of new active lesions or amount of clinical and MRI disease activity in short- and long-term. Regional classification of new active lesions over 5 years in cortical, subcortical and fossa posterior will allow prospective examination of cortical and SDGM atrophy and appearance of the new lesions.

Study Timeline

• Study Start: 2009-03
• Primary Completion: 2009-03
• Study First Submitted: 2012-05-01
• Study First Submitted QC: 2012-06-22
• Study First Posted: 2012-06-26
• Study Completion: 2014-12
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-11
• Last Update Posted: 2016-02-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 159

Inclusion Criteria

• Enrolled into the 2-year, double-blind, placebo-controlled ASA study and entered 3 year extension study
• MRI was performed on all patients using a 1.5 T magnet

Exclusion Criteria

• MRI images unable to be processed
• All 5 MRI time points not collected

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Mulitple Sclerosis	MRI	Patients with relapsing-remitting MS who had a MRI as part of their participation in the ASA study.

Primary Outcome Measures

Name	Time	Method
Lesion Activity	5 years	Assessment of lesion activity in the 0-6 and 6-12 months in the ASA study will allow the classification of patients with respect to the number of new active lesions over short-term (over 1 year) in order to examine predictive value of MRI disease activity in relation to development of long-term (5 year) cortical and SDGM atrophy.

Trial Locations

Locations (1)

Buffalo Neuroimaging Analysis Center; 🇺🇸 Buffalo, New York, United States