Validation of Multimodal Evoked Potentials (mmEP) for Predicting Disease Progression in Multiple Sclerosis (SMSC)

Validation of Multimodal Evoked Potentials (mmEP) for Predicting Disease Progression in Multiple Sclerosis: Sub-study Within the Swiss Multiple Sclerosis Cohort (SMSC)

Utility of Multimodal Evoked potentials (mmEP) for monitoring disease course and prediction of progression at different stages of Multiple Sclerosis (MS) is investigated

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Diagnostic test: multimodal evoked potentials (mmEP)

• Study Type: Observational
• Enrollment (Actual): 29

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Dep. of Neurology, Hospital of the University of Basel
  • Geneva, Switzerland
    • Hopitaux Universitaires de Geneve
  • Lugano, Switzerland, 6903
    • Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

MS patients participating in the Swiss Multiple Sclerosis Cohort Study (SMSC), regardless of MS-specific treatment

Description

Inclusion Criteria:

• diagnosed with a clinically isolated syndrome (CIS) or MS with a relapsing-remitting (RRMS) or a primary progressive disease course (PPMS):
• CIS: EDSS <= 5.5 within six months of first clinical event
• early RRMS: EDSS: <= 3.5 disease course of 5 up to 10 years
• late RRMS: EDSS: 2.0-5.5 inclusive disease course of 5 to 15 years
• PPMS: EDSS: 2.0-6.5 inclusive disease course up to 15 years
• participation in the Swiss Multiple Sclerosis Cohort Study (SMSC)
• mental ability to cooperate
• written informed consent

Exclusion Criteria:

• alcohol or substance abuse
• progressive disease other than Multiple Sclerosis
• psychiatric disorder requiring a treatment by a psychiatrist
• patients with movable metal implants, e.g. pace-maker, stents, deep brain stimulators etc.;(patients with jaw- or bone-fixed metal implants can be included)

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
clinically isolated syndrome (CIS); Multiple sclerosis (MS) with a clinically isolated syndrome (CIS) within six months of first clinical event. Multimodal evoked potentials (mmEP) assessments will take place at baseline, month 12 (from baseline), month 24 (from baseline) and month 36 (from baseline)	Diagnostic test: multimodal evoked potentials (mmEP); combination of visual evoked potentials (VEP) and motor evoked potentials (MEP) or the combination of VEP, MEP and somato-sensory evoked potentials (SSEP)
early relapsing-remitting late disease course (RRMS); MS with relapsing-remitting early disease course (RRMS) </= 10 years, Expanded Disability Status Scale (EDSS) </=3.5 EDSS: 1.0: No disability, minimal signs in 1 functional System (FS) 1.5: No disability, minimal signs in more than one FS 2.0: Minimal disability in one FS 2.5: Mild disability in one FS or minimal disability in two FS 3.0: Moderate disability in one FS, or mild disability in three or four FS. No impairment to Walking 3.5: Moderate disability in one FS and more than minimal disability in several others. No impairment to Walking. Multimodal evoked potentials (mmEP) assessments will take place at baseline, month 12 (from baseline), month 24 (from baseline) and month 36 (from baseline)	Diagnostic test: multimodal evoked potentials (mmEP); combination of visual evoked potentials (VEP) and motor evoked potentials (MEP) or the combination of VEP, MEP and somato-sensory evoked potentials (SSEP)
late relapsing-remitting late disease course (RRMS); MS with relapsing-remitting late disease course (late RRMS) of 5 to 15 years, EDSS: 2.0-5.5 inclusive EDSS: 4.0: Significant disability but self-sufficient and up and about some 12 hours a day. Able to walk without aid or rest for 500m 4.5: Significant disability but up and about much of the day, able to work a full day, may otherwise have some limitation of full activity or require minimal assistance. Able to walk without aid or rest for 300m 5.0: Disability severe enough to impair full daily activities and ability to work a full day without special provisions. Able to walk without aid or rest for 200m 5.5: Disability severe enough to preclude full daily activities. Able to walk without aid or rest for 100m. Multimodal evoked potentials (mmEP) assessments will take place at baseline, month 12 (from baseline), month 24 (from baseline) and month 36 (from baseline)	Diagnostic test: multimodal evoked potentials (mmEP); combination of visual evoked potentials (VEP) and motor evoked potentials (MEP) or the combination of VEP, MEP and somato-sensory evoked potentials (SSEP)
primary progressive disease course (PPMS); MS with a primary progressive disease course (PPMS) up to 15 years, EDSS: 2.0-6.5 inclusive EDSS: 6.0: Requires a walking aid - cane, crutch, etc. - to walk about 100m with or without resting 6.5: Requires two walking aids - pair of canes, crutches, etc. - to walk about 20m without resting. Multimodal evoked potentials (mmEP) assessments will take place at baseline, month 12 (from baseline), month 24 (from baseline) and month 36 (from baseline)	Diagnostic test: multimodal evoked potentials (mmEP); combination of visual evoked potentials (VEP) and motor evoked potentials (MEP) or the combination of VEP, MEP and somato-sensory evoked potentials (SSEP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
correlation of EP-sum-score (Σ-EP) and the Expanded Disability Status Scale (EDSS)	logistic regression model will be used to predict worsening in EDSS defined by a 1-point-change (0.5 if EDSS is 5.5 or higher) at year 3	3 years

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Peter Fuhr, Prof., Dep. of Neurology, Hospital of the University of Basel

Publications and helpful links

General Publications

• Hardmeier M, Schlaeger R, Lascano AM, Toffolet L, Schindler C, Gobbi C, Lalive P, Kuhle J, Kappos L, Fuhr P. Prognostic biomarkers in primary progressive multiple sclerosis: Validating and scrutinizing multimodal evoked potentials. Clin Neurophysiol. 2022 May;137:152-158. doi: 10.1016/j.clinph.2022.02.019. Epub 2022 Mar 7.
• Hardmeier M, Fuhr P. Multimodal Evoked Potentials as Candidate Prognostic and Response Biomarkers in Clinical Trials of Multiple Sclerosis. J Clin Neurophysiol. 2021 May 1;38(3):171-180. doi: 10.1097/WNP.0000000000000723.
• Hardmeier M, Schindler C, Kuhle J, Fuhr P. Validation of Quantitative Scores Derived From Motor Evoked Potentials in the Assessment of Primary Progressive Multiple Sclerosis: A Longitudinal Study. Front Neurol. 2020 Jul 24;11:735. doi: 10.3389/fneur.2020.00735. eCollection 2020.
• Hardmeier M, Jacques F, Albrecht P, Bousleiman H, Schindler C, Leocani L, Fuhr P. Multicentre assessment of motor and sensory evoked potentials in multiple sclerosis: reliability and implications for clinical trials. Mult Scler J Exp Transl Clin. 2019 May 1;5(2):2055217319844796. doi: 10.1177/2055217319844796. eCollection 2019 Apr-Jun.

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2015
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: July 26, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (Actual): August 15, 2018

Study Record Updates

• Last Update Posted (Actual): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Expanded Disability Status Scale (EDSS); Motor evoked potentials; Multimodal Evoked potentials; Visual evoked potentials; Somato-sensory evoked potentials
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease Attributes; Multiple Sclerosis; Sclerosis; Disease Progression
• Other Study ID Numbers: 2016-01818; me14Fuhr

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No