Central and Peripheral Nervous System Changes as Markers of Disease Progression in Multiple Sclerosis

NCT03401307 | Completed DMC

• 1 other identifier: SDUSF-2016-106 - (660)
• Study Type: observational
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

OBJECTIVE To investigate neurodegeneration and demyelination in the central and peripheral nervous system in multiple sclerosis linked to disease progression and mechanisms that can explain different responses to Fampridine treatment in MS patients with walking disability. METHOD The study is a prospective cohort follow-up study with 98 participants with MS and walking disability. Participants are identified as responders or non-responders to Fampridine treatment prior to the study. Participants will undergo MRI of the cerebrum with lesion load quantification, neurophysiological tests comprised of motor evoked potentials and electroneurographic examination, blood samples examining KIR4.1 antibodies, brain derived neurotrophic factor (BDNF), myelin protein zero (MPZ), peripheral myelin protein 22 (PMP22), p75-nerve growth factor receptor (p75NGFR) and anti-myelin associated glycoprotein (anti-MAG). The presence of SORCS-3 gene mutation will also be examined, as will cerebrospinal fluid levels of myelin basic protein, neurofilament heavy and light chains. Functional test of Timed 25-foot walk test (T25FW) will identify response to Fampridine treatment. A functional test battery will further detail function of upper extremities and cognition. CONCLUSION This study will add to the understanding of neurodegeneration and demyelination in CNS and PNS in patients with MS having walking disability. This will impact clinical decision-making by improving organization of immunomodulatory treatment, identifying biomarkers thus facilitating earlier treatment and improving patient control, information and education.

Conditions

Multiple Sclerosis; Neurodegeneration; Central Nervous System Lesion; Peripheral Nervous System Problem; Neurologic Deficits; Drug Effect; Genetic Disease; Neurophysiologic Abnormality

Outcome Measures

Primary Outcomes (1)

• Timed 25-Foot Walk Test (T25FW)

  The patient walks 25 feet as fast as possible. The test is repeated twice and the mean is used as the test result. This functional test measures walking speed and acceleration. This functional test has a high inter-rater and test-retest reliability and shows evidence of good concurrent validity. Hobart et al. have estimated the MCID for T25FW as an improvement \>20% and Jensen et al. have recently estimated it to 17.8% when based on data distribution approach.

  Baseline up to 6, 12 and 18 months.

Secondary Outcomes (9)

• Twelve Item MS Walking Scale (MSWS-12)

  Baseline up to 6, 12 and 18 months.

• Guys Neurological Disability Scale (GNDS)

  Baseline up to 6, 12 and 18 months.

• 5-Times-Sit-to-Stand Test (5-STS)

  Baseline up to 6, 12 and 18 months.

• The Six Spot Step Test (SSST)

  Baseline up to 6, 12 and 18 months.

• Antibodies

  Baseline up to 12 months.

Study Arms (2)

Responders to Fampridine Treatment

Participants, who are classified as responders to Fampridine treatment, have already been identified in the MS-centers in the Region of Southern Denmark, where they undergo outpatient treatment and clinical controls. A 2-week Fampridine treatment phase, as described in the trial outline section, has been used to identify responders to Fampridine. Participants who improve with ≥20% on the T25FW are categorized as responders.

Non-Responders to Fampridine Treatment

Participants, who are classified as non-responders to Fampridine treatment, have already been identified in the MS-centers in the Region of Southern Denmark, where they undergo outpatient treatment and clinical controls. A 2-week Fampridine treatment phase, as described in the trial outline section, has been used to identify non-responders to Fampridine. Participants who do not improve with ≥20% on the T25FW are categorized as non-responders.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants in this cohort will be recruited from the four Multiple Sclerosis Centers in the Region of Southern Denmark (Sønderborg, Odense, Vejle/Kolding and Esbjerg), which (as of January 2016) have approximately 3600 patients with MS. Participants, who are classified as responders to Fampridine treatment, have already been identified in the MS-centers in the Region of Southern Denmark, where they undergo outpatient treatment and clinical controls. A 2-week Fampridine treatment phase, as described in the trial outline section, has been used to identify responders to Fampridine. Participants who improve with ≥20% on the T25FW are categorized as responders.

You may qualify if:

• Participants are diagnosed with MS according to the McDonald criteria.
• Categorized as responder or non-responder to Fampridine treatment.
• Age in the range of 18-65 years.
• Extended Disability Status Scale (EDSS) 4-7 points.
• Pyramidal Functions Score ≥ 2 in the Kurtzke Functional Systems Scores (FSS).

You may not qualify if:

• Simultaneous use of medications that inhibit the organic cation transporter (OCT2).
• History of epileptic seizures.
• Clinically manifest heart-, liver-, kidney- (glomerular filtration rate \< 80 ml/min), pulmonary disease, diabetes, alcohol intake exceeding the National Institute of Health's recommendations and pregnancy.

Sponsors & Collaborators

• University of Southern Denmark: lead
• Region of Southern Denmark: collaborator

Study Sites (1)

Department of Neurology (Skleroseklinikken), Sygehus Sønderjylland

Sønderborg, Jylland, 6400, Denmark

Location

Related Publications (2)

• Mamoei S, Jensen HB, Pedersen AK, Nygaard MKE, Eskildsen SF, Dalgas U, Stenager E. Clinical, Neurophysiological, and MRI Markers of Fampridine Responsiveness in Multiple Sclerosis-An Explorative Study. Front Neurol. 2021 Oct 26;12:758710. doi: 10.3389/fneur.2021.758710. eCollection 2021.

  PMID: 34764932 DERIVED

• Mamoei S, Jensen HB, Dalgas U, Zijdewind I, Pedersen AK, Nygaard MKE, Eskildsen SF, Stenager E. A cross-sectional comparison of performance, neurophysiological and MRI outcomes of responders and non-responders to fampridine treatment in multiple sclerosis - An explorative study. J Clin Neurosci. 2020 Dec;82(Pt A):179-185. doi: 10.1016/j.jocn.2020.10.034. Epub 2020 Nov 15.

  PMID: 33317729 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

DNA samples from blood for gene testing of the SORCS-3 gene.

MeSH Terms

Conditions

Multiple Sclerosis; Nerve Degeneration; Neurologic Manifestations; Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Ph.D.-Fellow

Study Record Dates

• First Submitted: January 4, 2018
• First Posted: January 17, 2018
• Study Start: August 1, 2017
• Primary Completion: June 20, 2020
• Study Completion: December 1, 2020
• Last Updated: October 14, 2021

Record last verified: 2021-10

Locations

DK (1)