Spinal Cord Stimulation for Poststroke Spasticity

Official title

Spinal Cord Stimulation for Poststroke Spasticity: a Multicentre, Double-blind, Randomised, Sham-controlled Trial (SCS-PSS)

Overview

The goal of this clinical trial is to learn whether spinal cord stimulation (SCS) is effective in treating post-stroke spasticity in adults. It will also evaluate the safety of the implanted SCS system. The main questions it aims to answer are: 1. Does active SCS reduce limb spasticity compared with sham stimulation? 2. What device-related problems do participants experience during the study? All participants receive the same implantation and programming procedures,but no therapeutic stimulation(0 mA) for sham SCS group duringthe first 6 weeks after randomization. Participants will: 1. Have an SCS system surgically implanted 2. Be randomly assigned to receive active SCS or sham SCS for 6 weeks 3. After completion of the 6-week randomized comparison period, active stimulation will be initiated for all participants. 4. Attend a post-operative visit within 3 to 7 days after surgery for device activation or sham activation, programming, safety checks, and study assessments 5. Attend follow-up visits for study assessments at approximately 6, 12, 24 weeks, 1 year and 2 years after randomization 6. Complete assessments of muscle spasticity, joint range of motion, motor function, walking ability, daily functioning, pain, and quality of life 7. Report any medical problems or device-related problems during the study

Detailed description

Post-stroke spasticity is a common disabling complication of ischemic or hemorrhagic stroke. It can lead to abnormal muscle tone, restricted joint movement, impaired motor function, pain, and reduced independence in daily activities. Current treatments include rehabilitation therapy, oral antispastic medications, and botulinum toxin injections, but some patients continue to have clinically significant spasticity despite these treatments. Spinal cord stimulation (SCS) is a neuromodulation technique that delivers electrical stimulation to the spinal cord and may help regulate abnormal spinal motor circuits and reduce spasticity.

Previous exploratory studies have suggested that SCS may reduce limb spasticity and improve muscle strength, motor coordination, and functional movement after stroke. However, the available evidence is mainly based on small or exploratory studies, and the safety and efficacy of SCS for post-stroke spasticity have not yet been confirmed in a large, randomized, sham-controlled clinical trial. Therefore, a well-designed controlled study is needed to determine whether the observed improvements are caused by active SCS and to further evaluate device-related safety.

The Spinal Cord Stimulation for Post-Stroke Spasticity study (SCS-PSS study) is a prospective, multicenter, double-blind, randomized, sham-controlled clinical trial designed to evaluate the safety and efficacy of an implanted SCS system for adults with post-stroke spasticity. The study will enroll 92 participants with stable unilateral upper- or lower-limb spasticity after ischemic or hemorrhagic stroke who have not achieved their treatment goals with previous treatments. All participants will undergo implantation of an SCS system and will then be randomized in a 1:1 ratio to receive either active SCS or sham SCS during the first 6 weeks after randomization. Participants will attend a postoperative visit within 3 to 7 days for active or sham device activation, programming, safety assessment, and study evaluations. At 6 weeks after randomization, all participants will receive active stimulation and will continue follow-up through 24 weeks. In addition, they will undergo long-term follow-up for up to 2 years to further evaluate the durability of treatment effects and the long-term safety of the implanted SCS system. The primary outcome is the change from baseline to 6 weeks after randomization in the mean Modified Ashworth Scale score of primary target muscle groups. Additional outcomes include joint range of motion, motor function, walking ability, functional independence, pain, quality of life, adverse events, serious adverse events, and device deficiencies.

Interventions

• Device Active spinal cord stimulation
  Participants will receive therapeutic electrical stimulation through the implanted spinal cord stimulation system beginning on Day 0, defined as the day of active or sham activation within 3-7 days after surgery. An individualized SCS programming strategy will be used. Initial stimulation parameters will include a frequency of 40-60 Hz, a pulse width of 200-300 μs, and a low starting amplitude that will be gradually increased according to participant tolerance. For participants with concomitant
• Device Sham spinal cord stimulation
  Participants will undergo the same implantation and programming procedures. On Day 0, the implanted system will be turned on, but the stimulation amplitude will be set to 0 mA so that no effective electrical stimulation is delivered during the 6-week randomized comparison period. After completion of the Week 6 assessment, participants will receive active SCS using the same individualized programming principles as the Active SCS Group. Active stimulation will continue through the 24-week follow-u

Primary outcome measures

• Change in Mean Modified Ashworth Scale Score of the Primary Target Muscle Groups From Baseline to Week 6 [Time frame: Baseline to Week 6 after randomization]

Secondary outcome measures (9)

• Change in Modified Ashworth Scale Scores of the Primary Target Muscle Groups From Baseline [Time frame: Day 0, Week 6, Week 12, Week 24, Year 1, and Year 2 after randomization]
• Proportion of Participants With an Improvement in Mean Modified Ashworth Scale Score of at Least 1 Point [Time frame: Day 0, Week 6, Week 12, Week 24, Year 1, and Year 2 after randomization]
• Change in Active and Passive Joint Range of Motion From Baseline [Time frame: Day 0, Week 6, Week 12, Week 24, Year 1, and Year 2 after randomization]
• Change in Fugl-Meyer Assessment Score From Baseline [Time frame: Day 0, Week 6, Week 12, Week 24, Year 1, and Year 2 after randomization]
• Change in Functional Independence Measure Score From Baseline [Time frame: Day 0, Week 6, Week 12, Week 24, Year 1, and Year 2 after randomization]
• Change in Physician Global Assessment Score From Baseline [Time frame: Day 0, Week 6, Week 12, Week 24, Year 1, and Year 2 after randomization]
• Change in 10-Meter Walk Test Performance From Baseline [Time frame: Day 0, Week 6, Week 12, Week 24, Year 1, and Year 2 after randomization]
• Change in EQ-5D-5L Score From Baseline [Time frame: Day 0, Week 6, Week 12, Week 24, Year 1, and Year 2 after randomization]
• Change in Visual Analogue Scale Score From Baseline [Time frame: Day 0, Week 6, Week 12, Week 24, Year 1, and Year 2 after randomization]

Eligibility criteria

Inclusion criteria

• Aged ≥18 years and <75 years, regardless of sex;
• Diagnosed with ischemic or hemorrhagic stroke, with unilateral or single-limb motor dysfunction persisting for at least 6 months;
• The primary brain lesion and its underlying cause are clinically stable;
• Presence of unilateral upper- or lower-limb spasticity, with a Modified Ashworth Scale (MAS) grade of ≥2 in at least two muscle groups of the affected limb;
• Post-stroke limb dysfunction has not reached the treatment goal despite previous interventions, such as physical therapy and oral medications, and the participant's condition has shown no recent improvement;
• The type and dose of existing rehabilitation therapy and oral antispastic medications must remain unchanged during the study;
• Willing and able to complete all study visits and procedures;
• Able to understand the study and provide written informed consent.

Exclusion criteria

• Any contraindication to spinal cord stimulation surgery;
• Uncontrolled refractory epilepsy;
• Presence of tonic spasticity, such as decorticate rigidity or decerebrate rigidity;
• Poorly controlled severe psychiatric or cognitive impairment, defined as a Beck Depression Inventory-II score >25 or a Mini-Mental State Examination score <24;
• Active systemic infection;
• Presence of an implanted neurostimulator or drug delivery system;
• Botulinum toxin treatment within 4 months before enrollment;
• Plans to initiate any new treatment during the study that may affect limb movement, including chemical denervation therapies (such as botulinum toxin), oral antispastic medications, surgical procedures (such as peripheral neurotomy or contralateral C7 nerve transfer), or other physical therapy interventions;
• Pregnancy, breastfeeding, or planned pregnancy during the study;
• The participant or family is unable or unwilling to participate in long-term SCS treatment management;
• Participation in another clinical study within 4 weeks before signing informed consent;
• Any other condition that, in the investigator's judgment, makes the individual unsuitable for participation 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

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• China-Japan Friendship Hospital — Beijing

Publications

• Creamer M, Cloud G, Kossmehl P, Yochelson M, Francisco GE, Ward AB, Wissel J, Zampolini M, Abouihia A, Berthuy N, Calabrese A, Loven M, Saltuari L. Intrathecal baclofen therapy versus conventional medical management for severe poststroke spasticity: results from a multicentre, randomised, controlled, open-label trial (SISTERS). J Neurol Neurosurg Psychiatry. 2018 Jun;89(6):642-650. doi: 10.1136/jn PMID 29326296
• Gracies JM, Brashear A, Jech R, McAllister P, Banach M, Valkovic P, Walker H, Marciniak C, Deltombe T, Skoromets A, Khatkova S, Edgley S, Gul F, Catus F, De Fer BB, Vilain C, Picaut P; International AbobotulinumtoxinA Adult Upper Limb Spasticity Study Group. Safety and efficacy of abobotulinumtoxinA for hemiparesis in adults with upper limb spasticity after stroke or traumatic brain injury: a doub PMID 26318836
• Riva N, Mora G, Soraru G, Lunetta C, Ferraro OE, Falzone Y, Leocani L, Fazio R, Comola M, Comi G; CANALS Study Group. Safety and efficacy of nabiximols on spasticity symptoms in patients with motor neuron disease (CANALS): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2019 Feb;18(2):155-164. doi: 10.1016/S1474-4422(18)30406-X. Epub 2018 Dec 13. PMID 30554828
• Brashear A, Gordon MF, Elovic E, Kassicieh VD, Marciniak C, Do M, Lee CH, Jenkins S, Turkel C; Botox Post-Stroke Spasticity Study Group. Intramuscular injection of botulinum toxin for the treatment of wrist and finger spasticity after a stroke. N Engl J Med. 2002 Aug 8;347(6):395-400. doi: 10.1056/NEJMoa011892. PMID 12167681
• de Freitas RM, Bhatia S, Sorensen E, Verma N, Carranza E, Ensel S, Borda L, Boos A, Goldsmith J, Fisher LE, Fields DP, Powell MP, Gordon S, Balzer J, Friedlander RM, Wittenberg GF, Gerszten PC, Krakauer JW, Pirondini E, Weber DJ, Capogrosso M. Spinal cord stimulation for upper limb motor function in people with chronic post-stroke hemiparesis: a feasibility trial. Nat Med. 2026 Jun 4. doi: 10.1038 PMID 42243548
• Lorach H, Galvez A, Spagnolo V, Martel F, Karakas S, Intering N, Vat M, Faivre O, Harte C, Komi S, Ravier J, Collin T, Coquoz L, Sakr I, Baaklini E, Hernandez-Charpak SD, Dumont G, Buschman R, Buse N, Denison T, van Nes I, Asboth L, Watrin A, Struber L, Sauter-Starace F, Langar L, Auboiroux V, Carda S, Chabardes S, Aksenova T, Demesmaeker R, Charvet G, Bloch J, Courtine G. Walking naturally after PMID 37225984
• Rowald A, Komi S, Demesmaeker R, Baaklini E, Hernandez-Charpak SD, Paoles E, Montanaro H, Cassara A, Becce F, Lloyd B, Newton T, Ravier J, Kinany N, D'Ercole M, Paley A, Hankov N, Varescon C, McCracken L, Vat M, Caban M, Watrin A, Jacquet C, Bole-Feysot L, Harte C, Lorach H, Galvez A, Tschopp M, Herrmann N, Wacker M, Geernaert L, Fodor I, Radevich V, Van Den Keybus K, Eberle G, Pralong E, Roulet M PMID 35132264
• Francisco GE, McGuire JR. Poststroke spasticity management. Stroke. 2012 Nov;43(11):3132-6. doi: 10.1161/STROKEAHA.111.639831. Epub 2012 Sep 13. No abstract available. PMID 22984012

Identifiers

NCT: NCT07744659 · SCS-PNS0102&PINS-C2-01-53

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗