Proof of concept studies for tissue-protective agents in multiple sclerosis

• Published in: Multiple sclerosis Vol. 15; no. 5; pp. 542 - 546
• Main Authors: Mehta, LR, Schwid, SR, Arnold, DL, Cutter, GR, Aradhye, S, Balcer, LJ, Calabresi, PA, Cohen, JA, Cole, PE, Glanzman, R, Goelz, S, Inglese, M, Kapoor, R, Kappos, L, Kreitman, R, Lublin, FD, Mann, A, Marrie, RA, O'Looney, P, Polman, CH, Ravina, BM, Reingold, SC, Richert, JR, Sandrock, AW, Waubant, E
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-05-2009; Sage Publications; Sage Publications Ltd
• Subjects: Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Humans; Medical sciences; Multiple Sclerosis - drug therapy; Multiple Sclerosis - pathology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Neuroprotective Agents - therapeutic use; Randomized Controlled Trials as Topic; tissue protection; clinical trial designs; multiple sclerosis; outcome measurement; Prevention; Nervous system diseases; Multiple sclerosis; Central nervous system disease; Degenerative disease; Inflammatory disease
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1177/1352458508101939

Background
There is considerable interest in tissue-protective treatments for multiple sclerosis (MS).
Methods and Objectives
We convened a group of MS clinical trialists and related researchers to discuss designs for proof of concept studies utilizing currently available data and assessment methods.
Results
Our favored design was a randomized, double-blind, parallel-group study of active treatment versus placebo focusing on changes in brain volume from a post-baseline scan (3–6 months after starting treatment) to the final visit 1 year later. Study designs aimed at reducing residual deficits following acute exacerbations are less straightforward, depending greatly on the anticipated rapidity of treatment effect onset.
Conclusions
The next step would be to perform one or more studies of potential tissue-protective agents with these designs in mind, creating the longitudinal data necessary to refine endpoint selection, eligibility criteria, and sample size estimates for future trials.