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

Multiple Sclerosis, Relapsing-remitting Clinical Trial

— ASA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01628315
• Other study ID #: ASA
• Status: Completed
• Phase: N/A
• First received: May 1, 2012
• Last updated: February 11, 2016
• Start date: March 2009
• Est. completion date: December 2014

Study information

• Verified date: February 2016
• Source: University at Buffalo
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 159
• Est. completion date: December 2014
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Observational Model: Cohort, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting

Intervention

Device:
• MRI
Annual MRIs as part of participation in the ASA study.

Locations

Country	Name	City	State
United States	Buffalo Neuroimaging Analysis Center	Buffalo	New York

Sponsors (3)

Lead Sponsor	Collaborator
University at Buffalo	Charles University, Czech Republic, General University Hospital, Prague

Country where clinical trial is conducted

United States, 

References & Publications (4)

Bergsland N, Horakova D, Dwyer MG, Dolezal O, Seidl ZK, Vaneckova M, Krasensky J, Havrdova E, Zivadinov R. Subcortical and cortical gray matter atrophy in a large sample of patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis. AJNR Am J Neuroradiol. 2012 Sep;33(8):1573-8. doi: 10.3174/ajnr.A3086. Epub 2012 Apr 12. — View Citation

Havrdova E, Zivadinov R, Krasensky J, Dwyer MG, Novakova I, Dolezal O, Ticha V, Dusek L, Houzvickova E, Cox JL, Bergsland N, Hussein S, Svobodnik A, Seidl Z, Vaneckova M, Horakova D. Randomized study of interferon beta-1a, low-dose azathioprine, and low-dose corticosteroids in multiple sclerosis. Mult Scler. 2009 Aug;15(8):965-76. doi: 10.1177/1352458509105229. Epub 2009 May 22. — View Citation

Horakova D, Cox JL, Havrdova E, Hussein S, Dolezal O, Cookfair D, Dwyer MG, Seidl Z, Bergsland N, Vaneckova M, Zivadinov R. Evolution of different MRI measures in patients with active relapsing-remitting multiple sclerosis over 2 and 5 years: a case-control study. J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):407-14. Epub 2007 Jun 5. — View Citation

Horakova D, Dwyer MG, Havrdova E, Cox JL, Dolezal O, Bergsland N, Rimes B, Seidl Z, Vaneckova M, Zivadinov R. Gray matter atrophy and disability progression in patients with early relapsing-remitting multiple sclerosis: a 5-year longitudinal study. J Neurol Sci. 2009 Jul 15;282(1-2):112-9. doi: 10.1016/j.jns.2008.12.005. Epub 2009 Jan 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lesion Activity	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.	5 years	No