Spinal Cord Stimulation Combined With Motor Training in Non-Traumatic SCI: A Prospective Interventional Study (Neuro-scs-002)

Evaluation of Spinal Cord Stimulation Assisted by Motor Rehabilitation Training for Restoring Motor Function in Non-traumatic Spinal Cord Injury: an Interventional, Prospective, Monocentric Study

Interventional prospective longitudinal on the evaluation of spinal cord stimulation (SCS) assisted by motor rehabilitation training for restoring motor function in patients with non-traumatic spinal cord injury (SCI). The investigators will enroll ten research participants with clinically incomplete/complete SCI (patients with paraplegia or severe paraparesis) who will undergo SCS subsequently assisted by motor rehabilitation training for restoring motor function at IRCCS Ospedale San Raffaele, Milan, Italy. The main goal of the project is to evaluate the improvement in motor function generated by the combination of SCS and locomotor training. In line with recently published studies, the investigators propose that daily locomotor training in the presence of SCS with continuous stimulation parameters setting will enable the SCI individuals to stand and step independently while bearing full weight.

Study Overview

• Status: Not yet recruiting
• Conditions: Spinal Cord Disease; Spinal Cord Injuries (Complete and Incomplete)
• Intervention / Treatment: Procedure: Spinal cord stimulation surgery (device implant) and motor rehabilitation

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20132
    • IRCCS Ospedale San Raffaele
    • Principal Investigator: Pietro Mortini, MD
    • Contact: Luigi Albano, MD, PhD; Phone Number: +39 0226435568; Email: albano.luigi@hsr.it
    • Principal Investigator: Luigi Albano, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of NTSCI at least one year before presentation;
2. Complete or incomplete spinal cord damage (ASIA grade A, B or C) conditioning chronic neuropathic pain and motor impairment;
3. Age ≥ 18 years;
4. Indication to spinal cord stimulation surgery for chronic pain;
5. Being unable to stand or step independently;
6. No current anti-spasticity medication regimen;
7. No botox injections in the prior 3 months;
8. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study;
9. Willingness and ability to comply with scheduled visits and other trial procedures.

Exclusion Criteria:

1. Any person unable to lie still within the environment of the MRI scanner for the required period to perform the study and those where MRI scanning is contraindicated;
2. Pregnancy or breastfeeding;
3. Any significant psychiatric disease;
4. Use of illicit drugs;
5. Unstable medical condition without cardiopulmonary disease or dysautonomia that would contraindicate standing or stepping;
6. Painful musculoskeletal dysfunction, unhealed fracture, contracture, pressure sore, or urinary tract infection that might interfere with stand or step training;
7. Spinal cord involvement above the D1 segment;
8. Severe peripheral neuropathies or damage to the cauda equine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Individuals with functionally complete/incomplete non-traumatic spinal cord injury; Individuals with functionally complete/incomplete non-traumatic spinal cord injury who will undergo SCS for chronic pain

Procedure: Spinal cord stimulation surgery (device implant) and motor rehabilitation; The first part of the study will involve a preoperative evaluation. Participants' clinical history, neurological, neurophysiological and advanced brain/spine MRI examination will be assessed (Part 1). Subsequently, participants will undergo spinal cord stimulation surgery which involves the implantation of a medical device (Part 2). After the surgery, the research participants will be hospitalized at the Neurosurgery Unit (5-14 days) to monitor the incision site (Part 3). Thereafter, the patients will be moved (for at least 6 weeks) to the Rehabilitation Unit in order to identify appropriate stimulation parameters for inducing stepping and standing and for starting training. The combination of epidural stimulation with manual step/stand training will be thus evaluated (Part 4). Patients will be finally assessed by clinical evaluation, advanced MRI and neurophysiological examination to study the brain, spine and peripheral functions after six months (Part 5).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor changes (MRC)	The Medical Research Council's (MRC) scale of muscle power will be used to evaluate motor weakness. The MRC scale of muscle strength uses a score from Grade 5 (normal) to Grade 0 (no visible contraction) to assess the power of a particular muscle group in relation to the movement of a single joint.	Before surgery, then monthly up to 6-month from surgery
Motor changes (LEFS)	The Lower Extremity Functional Scale (LEFS) will be used by clinicians as a measure of lower extremity function. It is a questionnaire containing 20 questions about a person's ability to perform everyday tasks (minimum score 0, maximum score 80).	Before surgery, then monthly up to 6-month from surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spasticity changes	The Modified Ashworth scale will be used to evaluate spasticity. This scale grades the muscle tone from 0 (normal) to 4 (severe spasticity).	Before surgery, then monthly up to 6-month from surgery
Longitudinal neurophysiological reorganization (electromyography)	Electromyography will be used to evaluate muscle response or electrical activity in response to a nerve's stimulation.	Before surgery and 6 months after procedure
Longitudinal neurophysiological reorganization (motor evoked potentials)	Motor evoked potentials will be used to evaluate electrical signals recorded from the descending motor pathways or from muscles following stimulation of motor pathways within the brain.	Before surgery and 6 months after procedure
Longitudinal neurophysiological reorganization (sensory evoked potentials)	Sensory evoked potentials will be used to assess electrical activity in the brain in response to sensory stimulation.	Before surgery and 6 months after procedure
Longitudinal brain and spine MRI reorganization	Structural and functional brain and spine MRI analysis.	Before surgery and 6 months after procedure
Chronic pain changes (MPQ)	The McGill Pain Questionnaire (MPQ) can be used to evaluate a person experiencing significant pain. It consists of 15 descriptors (11 sensory; 4 affective) which are rated on an intensity scale as 0 = none, 1 = mild, 2 = moderate or 3 = severe.	Before surgery and 6 months after procedure
Chronic pain changes (PCS)	The Pain Catastrophizing Scale (PCS) assesses the extent of catastrophic thinking. It assesses the extent of catastrophic thinking due to low back pain according to 3 components: rumination, magnification, and helplessness. It is a 13-item scale, with a total range of 0 to 52. Higher scores are associated with higher amounts of pain catastrophizing.	Before surgery and 6 months after procedure
Chronic pain changes (ASC-12)	12-item Allodynia Symptom Checklist (ASC-12) evaluates presence of allodynia and hypoesthesia.	Before surgery and 6 months after procedure

Collaborators and Investigators

• Sponsor: Albano Luigi
• Collaborators: Scuola Superiore Sant'Anna di Pisa

Publications and helpful links

General Publications

• Angeli CA, Boakye M, Morton RA, Vogt J, Benton K, Chen Y, Ferreira CK, Harkema SJ. Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury. N Engl J Med. 2018 Sep 27;379(13):1244-1250. doi: 10.1056/NEJMoa1803588. Epub 2018 Sep 24.
• Wagner FB, Mignardot JB, Le Goff-Mignardot CG, Demesmaeker R, Komi S, Capogrosso M, Rowald A, Seanez I, Caban M, Pirondini E, Vat M, McCracken LA, Heimgartner R, Fodor I, Watrin A, Seguin P, Paoles E, Van Den Keybus K, Eberle G, Schurch B, Pralong E, Becce F, Prior J, Buse N, Buschman R, Neufeld E, Kuster N, Carda S, von Zitzewitz J, Delattre V, Denison T, Lambert H, Minassian K, Bloch J, Courtine G. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. 2018 Nov;563(7729):65-71. doi: 10.1038/s41586-018-0649-2. Epub 2018 Oct 31.
• Gill ML, Grahn PJ, Calvert JS, Linde MB, Lavrov IA, Strommen JA, Beck LA, Sayenko DG, Van Straaten MG, Drubach DI, Veith DD, Thoreson AR, Lopez C, Gerasimenko YP, Edgerton VR, Lee KH, Zhao KD. Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nat Med. 2018 Nov;24(11):1677-1682. doi: 10.1038/s41591-018-0175-7. Epub 2018 Sep 24.
• Romeni S, Losanno E, Emedoli D, Albano L, Agnesi F, Mandelli C, Barzaghi LR, Pompeo E, Mura C, Alemanno F, Tettamanti A, Castellazzi P, Ciucci C, Fossati V, Toni L, Caravati H, Bandini A, Del Carro U, Agosta F, Filippi M, Iannaccone S, Mortini P, Micera S. High-frequency epidural electrical stimulation reduces spasticity and facilitates walking recovery in patients with spinal cord injury. Sci Transl Med. 2025 Jan 8;17(780):eadp9607. doi: 10.1126/scitranslmed.adp9607. Epub 2025 Jan 8.
• Albano L, Emedoli D, Agnesi F, Romeni S, Losanno E, Toni L, Fossati V, Ciucci C, Gasperotti F, Cociani L, Zucco G, Pompeo E, Mura C, Carpaneto J, Tettamanti A, Castelnovo V, Padul JD, Mandelli C, Barzaghi LR, Alemanno F, Caravati H, Butera C, Del Carro U, Castellano A, Falini A, Agosta F, Filippi M, Iannaccone S, Mortini P, Micera S. Epidural electrical stimulation facilitates motor recovery in spinal cord injury involving the conus medullaris: A case study. Med. 2025 Oct 10;6(10):100706. doi: 10.1016/j.medj.2025.100706. Epub 2025 May 27.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: February 9, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: chronic pain; rehabilitation; spasticity; neuromodulation; motor restoration
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Central Nervous System Diseases; Nervous System Diseases; Muscular Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Wounds and Injuries; Trauma, Nervous System; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Muscle Spasticity; Chronic Pain; Spinal Cord Injuries; Spinal Cord Diseases; Equipment and Supplies
• Other Study ID Numbers: Neuro-scs-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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