Pilot Study of tSCS for Improving Upper Limb Function in People With Multiple Sclerosis

Official title

Transcutaneous Electrical Spinal Stimulation (tSCS) for Improving Upper Limb Function in People With MS

Overview

The goal of this clinical trial is to evaluate whether non-invasive spinal cord neuromodulation with the SCONE™ device can improve upper limb function in people with multiple sclerosis. The study will investigate if combining SCONE™ therapy with rehabilitation exercises leads to improvements in arm and hand movement, and whether the therapy is safe and well tolerated in this patient population. Participants will receive non-invasive spinal cord stimulation with the SCONE™ device and perform rehabilitation exercises specifically focused on the upper limb.

Detailed description

This is a pilot, randomized, placebo-controlled study designed to evaluate the efficacy and safety of transcutaneous spinal cord stimulation (tSCS) in improving upper limb function in patients with Multiple Sclerosis (MS).

tSCS is a non-invasive neuromodulation technique that delivers low-intensity electrical impulses through the skin to specific spinal segments. This external stimulation aims to enhance spinal excitability and restore communication between the brain and spinal circuits affected by MS. Previous research in spinal cord injury has demonstrated functional improvements in motor performance with tSCS, suggesting its potential benefit in MS-related disability.

In this study, participants with clinically confirmed MS and upper limb impairment will first undergo a 6-week period of standard occupational therapy. After this run-in phase, they will be randomly assigned in a 1:1 ratio to receive either active tSCS or sham stimulation for an additional 6 weeks, while continuing occupational therapy. The intervention will be delivered at the rehabilitation center of Hospital de la Esperanza, in a seated position, using surface electrodes placed at the posterior cervical region. Sessions will last approximately 30 minutes, three times per week (preferably Monday, Wednesday, and Friday).

The sham condition will mimic the procedure using the same equipment and electrode placement but without delivering effective stimulation. After completion of the blinded phase, participants originally randomized to sham will be offered the opportunity to receive active tSCS in an open-label extension.

The primary efficacy endpoint is improvement in upper limb function, assessed by the Nine-Hole Peg Test (9HPT). Secondary endpoints include the Action Research Arm Test (ARAT), patient-reported outcomes (NeuroQOL - Upper Extremity Function, Modified Fatigue Impact Scale \[MFIS\], and Global Impression of Change \[GIC\]), and clinical safety measures.

tSCS is generally safe and well-tolerated. Reported side effects are typically mild and transient, including tingling, skin irritation, or muscle discomfort. Participants will be monitored throughout the study, and adverse events will be recorded.

This pilot trial will provide preliminary data on the clinical utility of tSCS in MS and inform the design of larger randomized controlled trials.

Interventions

• Device Active stimulation tSCS
  Active transcutaneous spinal cord stimulation (tSCS) delivered with the SCONE™ device. Electrical currents are applied non-invasively through surface electrodes placed on the skin over the spine. Sessions are combined with standardized upper limb rehabilitation therapy. Participants receive stimulation twice per week for 12 weeks.
• Device Sham: stimulations using a non-active electric stimulation
  Sham stimulation delivered with the SCONE™ device, using identical setup and procedures as the active intervention but without effective current. This procedure is designed to mimic the sensation and experience of active stimulation while delivering no therapeutic neuromodulation. Participants also perform standardized upper limb rehabilitation therapy twice per week for 12 weeks.Transcutaneous Spinal Cord Stimulation (tSCS) - Sham (SCONE™)
• Behavioral Occupational/Upper Limb Rehabilitation Therapy
  Standardized occupational therapy program focused on upper limb function. Sessions are delivered in combination with either active or sham transcutaneous spinal cord stimulation.

Primary outcome measures

• Change in Upper Limb Function (9-Hole Peg Test) [Time frame: Baseline and Week 12]

Secondary outcome measures (6)

• Change in Hand Grip Strength (Dynamometry) [Time frame: Baseline and Week 12]
• Change in Quality of Life (EQ-5D-5L) [Time frame: Baseline and Week 12]
• Change in Fatigue (Modified Fatigue Impact Scale - MFIS) [Time frame: Baseline and Week 12]
• Change in Manual Dexterity (Box and Block Test) [Time frame: Baseline and Week 12]
• Patient-Reported Upper Limb Function (Multiple Sclerosis Impact Scale - MSIS-29, upper limb subitems) [Time frame: Baseline and Week 12]
• Safety and Tolerability [Time frame: Baseline through Week 12]

Eligibility criteria

Inclusion criteria

• Age between 18 and 70 years.
• Diagnosis of Multiple Sclerosis (according to revised McDonald criteria).
• Upper limb dysfunction (9-Hole Peg Test score ≥ 20% slower than normative values).
• Stable disease-modifying treatment for ≥ 6 months before enrollment.
• Expanded Disability Status Scale (EDSS) score between 3.0 and 6.5.
• Ability to provide informed consent.

Exclusion criteria

• Relapse or corticosteroid treatment within the last 3 months.
• Severe spasticity of the upper limb (Modified Ashworth Scale > 3).
• Implanted electrical devices (pacemaker, spinal cord stimulator).
• Epilepsy or uncontrolled seizures.
• Severe psychiatric disorders or cognitive impairment interfering with study procedures.
• Pregnant or breastfeeding women.
• Participation in another interventional clinical trial within the last 3 months.

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

Double blind

Primary purpose

Other

Study locations

Spain · 1 center

• Hospital del Mar — Barcelona

Publications

• Inanici F, Samejima S, Gad P, Edgerton VR, Hofstetter CP, Moritz CT. Transcutaneous Electrical Spinal Stimulation Promotes Long-Term Recovery of Upper Extremity Function in Chronic Tetraplegia. IEEE Trans Neural Syst Rehabil Eng. 2018 Jun;26(6):1272-1278. doi: 10.1109/TNSRE.2018.2834339. PMID 29877852
• Moritz C, Field-Fote EC, Tefertiller C, van Nes I, Trumbower R, Kalsi-Ryan S, Purcell M, Janssen TWJ, Krassioukov A, Morse LR, Zhao KD, Guest J, Marino RJ, Murray LM, Wecht JM, Rieger M, Pradarelli J, Turner A, D'Amico J, Squair JW, Courtine G. Non-invasive spinal cord electrical stimulation for arm and hand function in chronic tetraplegia: a safety and efficacy trial. Nat Med. 2024 May;30(5):1276 PMID 38769431
• Tu YH, Stiles ML, Allen LV Jr, Olsen KM, Barton CI, Greenwood RB. Stability of amoxicillin trihydrate-potassium clavulanate in original containers and unit dose oral syringes. Am J Hosp Pharm. 1988 May;45(5):1092-9. PMID 3400652
• Barss TS, Parhizi B, Porter J, Mushahwar VK. Neural Substrates of Transcutaneous Spinal Cord Stimulation: Neuromodulation across Multiple Segments of the Spinal Cord. J Clin Med. 2022 Jan 27;11(3):639. doi: 10.3390/jcm11030639. PMID 35160091
• Waltz JM, Andreesen WH, Hunt DP. Spinal cord stimulation and motor disorders. Pacing Clin Electrophysiol. 1987 Jan;10(1 Pt 2):180-204. doi: 10.1111/j.1540-8159.1987.tb05947.x. PMID 2436177
• Wallin MT, Culpepper WJ, Campbell JD, Nelson LM, Langer-Gould A, Marrie RA, Cutter GR, Kaye WE, Wagner L, Tremlett H, Buka SL, Dilokthornsakul P, Topol B, Chen LH, LaRocca NG; US Multiple Sclerosis Prevalence Workgroup. The prevalence of MS in the United States: A population-based estimate using health claims data. Neurology. 2019 Mar 5;92(10):e1029-e1040. doi: 10.1212/WNL.0000000000007035. Epub 2 PMID 30770430

Identifiers

NCT: NCT07152145 · tSCS-MS-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗