Current therapies for multiple sclerosis (MS) inhibit the inflammatory response, but neither sufficiently inhibits ongoing degeneration within the brain nor provide potential repair to injured brain tissue. Consequently, there are no therapies with demonstrated efficacy in slowing, stopping, or reversing the progressive stage of MS, therefore representing an extreme unmet need in neurologic disease. Complicating matters, there are no biological or imaging markers with demonstrated utility for use in Phase 2 trials to screen putative therapies for progressive MS. This study proposes to both test the activity of a potential neuroprotection therapy - ibudilast - in progressive MS and test several candidate imaging measures for their utility in future studies of neuroprotection in progressive MS. We plan to conduct a 2-year;placebo-controlled trial of ibudilast in progressive MS. Multiple advanced imaging modalities will be used to evaluate the activity of ibudilast. At the conclusion of the tril, we will have a clear understanding of the effect of ibudilast on advanced imaging metrics and its safety and potential clinical benefit in progressive MS. Through additional analyses, we will determine which imaging metric provides the most robust and practical outcome for implementation in future clinical trials in progressive MS. Hopefully, this study will show efficac of ibudilast that leads to the first primary neuroprotective drug. Even if ibudilast is not found beneficial, the study will be crucial to the MS field by comparing imaging metrics to support practical Phase II trials for a group of MS patients for whom there is no treatment option.

Public Health Relevance

Progressive multiple sclerosis (MS) is a gradually progressive form of MS affecting approximately 200,000 Americans and is the leading cause of non-traumatic neurologic disability in young adults. There are both no therapies with demonstrated efficacy in progressive MS and no validated biomarkers to screen potential therapies in small, efficient proof-of-concept trials. This trial will both evaluate the activity a putative neuroprotetive therapy in a phase II clinical trial in progressive MS and also evaluate several potential imaging biomarkers to identify the most robust imaging measure of neurodegeneration. The results will have broad relevance to other neurodegenerative disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01NS082329-01A1S1
Application #
8803548
Study Section
Special Emphasis Panel (ZNS1-SRB-G (63))
Program Officer
Moy, Claudia S
Project Start
2013-07-15
Project End
2018-06-30
Budget Start
2013-07-15
Budget End
2014-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$585,071
Indirect Cost
$15,737
Name
Cleveland Clinic Lerner
Department
Neurology
Type
Schools of Medicine
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195