Abstract
BackgroundNo treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS). The Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) trial tests the safety and feasibility of treatment with a candidate cell-based therapy, and will inform the wider challenge of designing early phase clinical trials to evaluate putative neuroprotective therapies in progressive MS. Illustrated by the MSCIMS trial protocol, we describe a novel methodology based on detailed assessment of the anterior visual pathway as a model of wider disease processes - the "sentinel lesion approach".Methods/designMSCIMS is a phase IIA study of autologous mesenchymal stem cells (MSCs) in secondary progressive MS. A pre-test : post-test design is used with healthy controls providing normative data for inter-session variability. Complementary eligibility criteria and outcomes are used to select participants with disease affecting the anterior visual pathway.ResultsTen participants with MS and eight healthy controls were recruited between October 2008 and March 2009. Mesenchymal stem cells were successfully isolated, expanded and characterised in vitro for all participants in the treatment arm.ConclusionsIn addition to determining the safety and feasibility of the intervention and informing design of future studies to address efficacy, MSCIMS adopts a novel strategy for testing neuroprotective agents in MS - the sentinel lesion approach - serving as proof of principle for its future wider applicability.Trial registrationClinicalTrials.gov (NCT00395200).
Highlights
No treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS)
In addition to determining the safety and feasibility of the intervention and informing design of future studies to address efficacy, Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) adopts a novel strategy for testing neuroprotective agents in MS - the sentinel lesion approach - serving as proof of principle for its future wider applicability
This requires a combination of clinical outcome measures to register improved function in addition to the use of paraclinical observations and novel biomarkers that can inform on the mechanisms of therapeutic effect and detect benefits that lie below clinical thresholds
Summary
No treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS). Trial design for the assessment of putative neuroprotective agents in MS presents a range of challenges including the need to identify patients who will benefit from treatment as well as to provide information on the mode of action of any intervention [9] This requires clinical trial protocols that differ from those used in the evaluation of disease-modifying therapies in terms of both participant selection and measurement(s) of efficacy. Neuroprotective trial design must aim to select outcomes that are informative with respect to stages of the disease other than the relapsing-remitting phase, and which demonstrate the effects of targeting both immunological and neurobiological components of the complex pathogenesis This requires a combination of clinical outcome measures to register improved function in addition to the use of paraclinical observations and novel biomarkers that can inform on the mechanisms of therapeutic effect and detect benefits that lie below clinical thresholds. By providing a detailed methodological description, we aim to inform the development of trial design in the wider setting of neuroprotective therapies for progressive MS
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