RESTORES Trial: RESToration Of Rehabilitative Function With Epidural Spinal Stimulation (RS-01)

Spinal Cord Injury (SCI), being a devastating diagnosis, has little to no recovery which leads to a long-standing of debilitating impairment for affected patients. The National Neuroscience Institute (NNI) Neurosurgery team, together with our collaborators, will be embarking on a new clinical pilot trial named RESTORES: RESToration of Rehabilitative function with Epidural Spinal Stimulation. This study aims to investigate the feasibility of electrical stimulation via a spinal cord stimulator (SCS), which will be implanted into the study subjects, and advanced robotic neuro-rehabilitation to aid in improving neurological function in patients diagnosed with chronic SCI. A total of 3 patients, male and female participants, above the age of 21 who have been diagnosed with the condition for more than a year will be recruited for this study over a 2-year period. Rehab sessions will take place pre and post-surgical implant, assessing subject improvements.

Study Overview

• Status: Recruiting
• Conditions: Chronic Spinal Cord Injury
• Intervention / Treatment: Device: RESToration Of Rehabilitative function with Epidural spinal Stimulation

Detailed Description

Motor complete SCI is defined as American Spinal Injury Association (ASIA) impairment Grade A or B, with no motor function preserved below the level of injury. This in-turn results in significant catastrophic dysfunction and disability to the individual's physical and mental health, reducing quality of life and increasing caregiver burden which translates to high socioeconomic costs. The current treatments for chronic SCI involves aggressive rehabilitation to maximize residual neurological function and devices to compensate for neurological loss. However, neurological improvement is dismal, with 94.4% of patients demonstrating no neurological improvement 5-years post-injury. Experimental and electrophysiological observations revealed that spinal networks have the capacity to generate basic locomotor rhythmicity without supraspinal input to the cord. SCS, consisting of a small array of electrodes surgically implanted into the spinal epidural space stimulates afferent sensory pathways in specific patterns to drive voluntary and autonomically controlled motor responses. Activity-based training in conjunction with SCS has been shown to bolster neuroplasticity and recovery caudal to the injury site. The investigators aim to deliver epidural spinal stimulation via an implanted SCS and together with personalized advanced neuro-rehabilitation to study the improvement of neurological function after chronic SCI.

• Study Type: Interventional
• Enrollment (Anticipated): 3
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kai Rui Wan, MBBS; Phone Number: 63577538; Email: wan.kai.rui@singhealth.com

Study Locations

• Singapore
  • Singapore, Singapore
    • Recruiting
    • National Neuroscience Institute
    • Contact: Kai Rui Wan, MBBS; Phone Number: 63577538; Email: wan.kai.rui@singhealth.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

⦁ Inclusion Criteria

For inclusion in the study, the potential patient has to fulfil all of the following criteria:

1. 21 years old and older
2. Chronic (greater than one year) motor complete (AIS classification A or B) SCI
3. Spinal injury between the levels of Thoracic 2 (T2) to Lumbar 1 (L1)
4. Segmental reflexes that remain functional below the level of lesion

5. Able to perform the perioperative rehabilitation program as judged by the research team

   • Exclusion Criteria

Potential patients will be excluded from the trial if they fulfil any of the following criteria:

1. Significant medical co-morbidities that would significantly increase the risk of the operation
2. Severe dysautonomia with systolic blood pressure fluctuation less than 50 or more than 200mmHg on tilt table testing
3. Painful musculoskeletal dysfunction, contractures, unhealed fractures, pressure sores, severe spasticity, and osteoporosis
4. Significant psychological issues or ongoing drug abuse
5. Pregnancy and lactating patients
6. Progressive spinal cord disease

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

Other: Patients with motor complete chronic spinal cord injury

Device: RESToration Of Rehabilitative function with Epidural spinal Stimulation; Three patients with chronic motor SCI will be recruited in total for this study. The recruited patients will not be randomized nor blinded due to the nature of this study. Pre-op rehabilitation session will take place over 4 weeks. 1 month post-surgical implants, patients will undergo 24 weeks of rehabilitation. The training sessions may continue to take place after the stipulated 24 weeks as long the electrode remains implanted, and the patient is available.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events assessed by CTCAE v5.0	The adverse events in patient's with proposed surgical implantation and robotic neuro-rehabilitation during the course of study will be assessed. Particularly, during the first 6 months of the study and post implantation.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessing the improvement in motor outcomes post surgical implantation	Volitional control including independent locomotion with epidural spinal stimulation and robotic neuro-rehabilitation will be assessed to check for improvement in motor functions. This assessment will be done during rehabilitation session where the post-surgical movement results will be compared against the pre-surgical results for better understanding and study.	2 years
Assessing autonomic function post surgical implantation	The improvement in hemodynamic, bowel and bladder control with epidural spinal stimulation and robotic neuro-rehabilitation will be assessed continuously post surgical implantation	2 years

Collaborators and Investigators

• Sponsor: National Neuroscience Institute
• Collaborators: Tan Tock Seng Hospital; Agency for Science, Technology and Research

Publications and helpful links

General Publications

• Kirshblum S, Millis S, McKinley W, Tulsky D. Late neurologic recovery after traumatic spinal cord injury. Arch Phys Med Rehabil. 2004 Nov;85(11):1811-7. doi: 10.1016/j.apmr.2004.03.015.
• Lim PA, Tow AM. Recovery and regeneration after spinal cord injury: a review and summary of recent literature. Ann Acad Med Singap. 2007 Jan;36(1):49-57.
• Teo SH, Sew S, Backman C, Forwell S, Lee WK, Chan PL, Dean E. Health of people with spinal cord injury in Singapore: implications for rehabilitation planning and implementation. Disabil Rehabil. 2011;33(15-16):1460-74. doi: 10.3109/09638288.2010.533812. Epub 2010 Nov 20.
• Minassian K, Jilge B, Rattay F, Pinter MM, Binder H, Gerstenbrand F, Dimitrijevic MR. Stepping-like movements in humans with complete spinal cord injury induced by epidural stimulation of the lumbar cord: electromyographic study of compound muscle action potentials. Spinal Cord. 2004 Jul;42(7):401-16. doi: 10.1038/sj.sc.3101615.
• Minassian K, Persy I, Rattay F, Pinter MM, Kern H, Dimitrijevic MR. Human lumbar cord circuitries can be activated by extrinsic tonic input to generate locomotor-like activity. Hum Mov Sci. 2007 Apr;26(2):275-95. doi: 10.1016/j.humov.2007.01.005. Epub 2007 Mar 6.

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2022
• Primary Completion (Anticipated): May 30, 2024
• Study Completion (Anticipated): August 30, 2024

Study Registration Dates

• First Submitted: October 30, 2022
• First Submitted That Met QC Criteria: November 30, 2022
• First Posted (Actual): December 9, 2022

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Spinal cord injury; Implantation; Epidural spinal stimulation
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries
• Other Study ID Numbers: RS-01

Drug and device information, study documents

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