Feasibility and Reliability of Multimodal Evoked Potentials in an International Multicenter Setting

Multiple Sclerosis

motor evoked potential, somatosensory evoked potentials, biomarker

Study Objectives and Endpoints: Objective: The primary objective of the study is to evaluate the feasibility and test-retest reliability of MEP's and (SSEP's) in a multicenter clinical trial in healthy subjects and subjects with MS. Endpoints: The primary reliability endpoint will be the intraclass correlation coefficient (ICC) of the following evoked potential parameters

The establishment of a biomarker(s) that can predict a clinical response to therapy over the course of a 1-2 year clinical trial is critical for the expeditious development of treatments for Multiple Sclerosis (MS). Identification of this biomarker would enable shorter and smaller clinical trials resulting in the faster development of much needed treatments for MS, specifically neuro-reparative therapies. The etiology of disease progression is conduction block, demyelination and axonal degeneration. Evoked potentials provide a direct assessment of the underlying etiologies of disease progression in MS. They are a functional assessment of multiple pathways, including visual, motor and sensory, evaluating the integrity of myelin and axons. The variability of motor evoked potentials (MEP) measures has limited multimodal evoked potential (mmEP) use in international, multicenter clinical trials. MEP evaluation does significantly contribute to the predictive value of mmEP's. Recent advances in technology and establishment of standardized protocols for MEP reduces the variability associated with this procedure. The objective of this study is to evaluate the reliability and feasibility of MEP and SSEP in an international, multicenter trial so that mmEP can be further evaluated as a biomarker for disease progression. The rationale for this study is to explore the feasibility and reliability of MEP's and somatosensory evoked potentials (SSEP's) in a multicenter clinical trial for potential use as a biomarker that can predict clinical progression/improvement in international clinical trials evaluating remyelinating therapies. Study Objectives and Endpoints: Objective: The primary objective of the study is to evaluate the feasibility and test-retest reliability of MEP's and (SSEP's) in a multicenter clinical trial in healthy subjects and subjects with MS. Endpoints: The primary reliability endpoint will be the intraclass correlation coefficient (ICC) of the following evoked potential parameters Motor Evoked parameters that will be measured: * MEP latency * Central motor conduction time (CMCT) root latency methods * MEP amplitude * MEP amplitude to compound motor amplitude ratio (MEP-M ratio) for the right and left abductor digiti minimi (ADM) and the right and left tibialis anterior (TA) * Somatosensory evoked potential parameters will include Evoked potential latencies for both upper and lower limbs bilaterally. Study Design: This multinational, multicenter study will be conducted in healthy adult volunteers and MS patients to establish the feasibility and reliability of mmEP's. A total of 40 subjects, 10 (5 healthy and 5 MS) from each of the 4 sites will be enrolled. The study will consist of two visits, 1-30 days apart, during which subjects will be screened to confirm eligibility and will complete all specified study assessments. Study Locations: Canada, Germany, Switzerland and Italy, with 1 site in each country. Number of Planned Subjects: A minimum of 40 subjects are planned for this study. Subjects who withdraw from the study prior to completion of the second visit may be replaced at the discretion of the investigator. Study Population: This study will be conducted in subjects 25 to 58 years of age, inclusive, who are either healthy volunteers (HV) or have been diagnosed with clinically definite MS who have a detectable lesion by MEP or SSEP. Study Groups: Two groups, healthy volunteers and clinically definite MS will be included. Duration of Study Participation: Study duration for each subject will be two visits, the second visit schedule \>24 hours-30 days from the first visit Criteria for Evaluation: Key Study Assessments: Electrophysiological. MEP's and SSEPs will be measured in both upper and lower limbs bilaterally. All studies will be read locally and reviewed by a blinded reader at another center. The ICC of every measured evoked potential parameter will be determined on both the central and local reads.

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