Repetitive Transcranial Magnetic Stimulation (rTMS) in MS Induced Spastic Paraparesis

Official title

Non-Invasive Neuromodulation in MS Induced Spastic Paraparesis

Overview

Study the impact of rTMS on walking ability in people with Multiple Sclerosis (MS) induced spastic paraparesis and moderate walking disability.

Detailed description

Measure the impact of rTMS on overall disability level, walking endurance, quality of life parameters, and corroborate with EEG parameters of neural synchrony in patients with MS.

Interventions

• Device Repetitive Transcranial Magnetic Stimulation
  Treatment with the rTMS or sham rTMS will be scheduled daily 5x per week for a total of 6 consecutive weeks followed, after a 6 week pause, by another treatment session of 6 weeks where all patients will receive active rTMS treatment

Primary outcome measures

• Improvement of T25FWT (Timed 25-Foot Walk Test) [Time frame: 18 weeks]

Secondary outcome measures (2)

• 6MWT (Six minute Walk Test) [Time frame: 12 weeks]
• MSQoL (Multiple Sclerosis Quality of Life) [Time frame: 12 weeks]

Eligibility criteria

Inclusion criteria

• Signed informed consent.
• Age ≥ 18 years and less than 71 years.
• Diagnosis of MS according to the revised 2017 McDonald Criteria (Thompson et al. 2018).
• EDSS of 3.0 to 6.5 with a pyramidal functional system score of 3.0 or more.
• Neurologically stable with no change in symptom related medications or relapse for at least 30 days prior to screening.
• Patients will be allowed to continue fampridine provided they started more than 30 days prior to screening. They will not be allowed to start fampridine, any stimulant (modafenil, methylphenidate etc) or symptomatic treatment of spasticity (baclofen, tizanidine, botulinum toxin etc.) during the study.
• No change in disease modifying therapy for at least 3 months prior to screening.
• Ability to perform T25FWT, the MSQoL 6MWT Ability and willingness, in the investigator's opinion, to comply with the study protocol.

Exclusion criteria

• Know presence of other neurologic disorders, which in the opinion of the investigator could add to the patient's neurological disability within the timespan of the study.
• Evidence of clinically significant cardiovascular (including arrhythmias), psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, or gastrointestinal disease that, in the investigator's opinion, would preclude patient participation.
• Pregnant or breastfeeding or intending to become pregnant during the study.
• Any previous rTMS therapy for any indication.
• Presence of any contraindication to rTMS therapy such as but not limited to: CNS implanted devices, pacemaker.
• Any condition which in the opinion of the investigator will render the patient unsuitable to participate in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• Clinique Neuro-Outaouais — Gatineau

Publications

• Vickrey BG, Hays RD, Harooni R, Myers LW, Ellison GW. A health-related quality of life measure for multiple sclerosis. Qual Life Res. 1995 Jun;4(3):187-206. doi: 10.1007/BF02260859. PMID 7613530
• Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K, Galetta SL, Hartung HP, Kappos L, Lublin FD, Marrie RA, Miller AE, Miller DH, Montalban X, Mowry EM, Sorensen PS, Tintore M, Traboulsee AL, Trojano M, Uitdehaag BMJ, Vukusic S, Waubant E, Weinshenker BG, Reingold SC, Cohen JA. Diagnosis of multiple sclerosis: 2017 revisions PMID 29275977
• Schoonheim MM, Meijer KA, Geurts JJ. Network collapse and cognitive impairment in multiple sclerosis. Front Neurol. 2015 Apr 14;6:82. doi: 10.3389/fneur.2015.00082. eCollection 2015. No abstract available. PMID 25926813
• Rotenberg A, Bae EH, Muller PA, Riviello JJ Jr, Bourgeois BF, Blum AS, Pascual-Leone A. In-session seizures during low-frequency repetitive transcranial magnetic stimulation in patients with epilepsy. Epilepsy Behav. 2009 Oct;16(2):353-5. doi: 10.1016/j.yebeh.2009.08.010. Epub 2009 Sep 10. PMID 19747883
• Oosterveer DM, van den Berg C, Volker G, Wouda NC, Terluin B, Hoitsma E. Determining the minimal important change of the 6-minute walking test in Multiple Sclerosis patients using a predictive modelling anchor-based method. Mult Scler Relat Disord. 2022 Jan;57:103438. doi: 10.1016/j.msard.2021.103438. Epub 2021 Nov 30. PMID 34871859
• Joo EY, Han SJ, Chung SH, Cho JW, Seo DW, Hong SB. Antiepileptic effects of low-frequency repetitive transcranial magnetic stimulation by different stimulation durations and locations. Clin Neurophysiol. 2007 Mar;118(3):702-8. doi: 10.1016/j.clinph.2006.11.008. Epub 2007 Jan 16. PMID 17223384
• Goldman MD, Marrie RA, Cohen JA. Evaluation of the six-minute walk in multiple sclerosis subjects and healthy controls. Mult Scler. 2008 Apr;14(3):383-90. doi: 10.1177/1352458507082607. Epub 2007 Oct 17. PMID 17942508
• Gandhi OP. Electromagnetic fields: human safety issues. Annu Rev Biomed Eng. 2002;4:211-34. doi: 10.1146/annurev.bioeng.4.020702.153447. Epub 2002 Mar 22. PMID 12117757

Identifiers

NCT: NCT07159789 · CeV

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗