Functional Mobility, Gait, Lower Limb Functions, Mobility Impairment, Reduced Physical Activity, Spinal Cord Injury (SCI), Walking Impairment
Conditions
Keywords
Vagus nerve stimulation (VNS), Spinal cord injury (SCI), Closed-loop vagus nerve stimulation (CLV), ReWire System, Physical and rehabilitation therapy, XNerve Medical, Texas Biomedical Device Center (TxBDC), Gait, Reduced physical activity, Lower limb functions, Walking impairment, Mobility impairment, Functional mobility
Brief summary
The purpose of this study is to evaluate the safety, feasibility, and preliminary effectiveness of the ReWire system, which delivers vagus nerve stimulation (VNS) paired with lower limb rehabilitation to improve gait in individuals with mobility impairments resulting from chronic, incomplete spinal cord injury (SCI).
Detailed description
A randomized, multi-center, double-blinded sham-control early feasibility trial of participants implanted with the ReWire System for spinal cord injury (SCI) with and open label extension. During the pre-therapy phase, participants will undergo informed consent, baseline assessment, pre-operative evaluation, surgical implantation of the ReWire system, post-surgical assessment, and randomization. Following post-surgical assessment, participants will be block randomized in a 1:1 ratio to either active CLV (Immediate start group) or sham stimulation (Delayed start group) for the double-blind phase. In double-blind phase, participants will complete up to 18 sessions of lower limb rehabilitation paired with CLV (Immediate start group) or sham stimulation (Delayed start group). Participants will then undergo assessment after completion of all sessions. In open-label phase, all participants will receive up to an additional 18 sessions of CLV, regardless of their assignment in the double-blind phase. Participants will then undergo assessment after completion of all sessions. A final, follow-up assessment will be conducted approximately 4 weeks (a month) from the previous assessment and cessation of CLV. Long-term assessment of safety will be performed twice annually for up to 2 years from the date of implantation, following the completion of final assessment.
Interventions
DEVICECLV
The participants in this group will be implanted with the ReWire system and receive CLV in the double-blind phase
DEVICESham
The participants in this group will be implanted with the ReWire system and receive Sham in the double-blind phase
Sponsors
The University of Texas at Dallas
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
1:1 randomization of CLV vs. sham stimulation for 18 sessions post randomization, followed by up to 18 sessions of open label CLV for all participants
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
1. Ability to provide signed and dated informed consent. 2. Willingness and ability to comply with all study procedures and protocol requirements for the duration of the study. 3. Age 18 to 64 years. 4. Chronic, non-penetrating, motor incomplete spinal cord injury \[Association Impairment Scale (AIS) grade C or D\] occurring ≥12 months prior to enrollment, resulting in impairment in lower limb function. 5. Ambulatory with residual gait impairment attributable to spinal cord injury. 6. Self-selected gait speed of \< 0.8 m/s as measured by the 10 meter walk test. 7. Score of 2 or less on at least 4 measures on the Ambulation subsection of the SCI-Functional Independence scale (SCI-FIS). 8. In otherwise good general health as determined by medical history and physical examination. 9. Meets all clinical criteria for VNS implantation as determined by the Site PI and clinical care team.
Exclusion criteria
1. Any history of spinal cord injuries by penetrating traumatic, non-traumatic or congenital causes. 2. Evidence of right-sided recurrent laryngeal nerve injury on pre-operative laryngoscopy, if required (Note: Participants with a history of right-sided anterior cervical surgery must undergo laryngoscopy prior to surgical scheduling. A finding of right-sided recurrent laryngeal nerve injury results in exclusion). 3. Excessive scar tissue on intraoperative assessment that precludes safe implantation (Note: Participants with a history of left-sided anterior cervical surgery will undergo intraoperative assessment of scar tissue. If excessive scar tissue is deemed to preclude safe implantation, the procedure will be abandoned and the participant excluded for safety reasons. A history of left-sided anterior cervical surgery or prior recurrent laryngeal nerve injury alone does not result in exclusion). 4. Concomitant clinically significant brain injuries. 5. Deficits in language or attention that interfere with study participation. 6. Presence of any other implanted electrical stimulation device. 7. Prior injury to the vagus nerve. 8. Presence of any other implanted investigational device. 9. Neck circumference of \> 18.5 inches or significant overlying tissue and/or scarring that may hinder device communication. 10. Psychiatric, psychosocial, and/or cognitive disorder or impairment that could interfere with study participation as assessed by medical evaluation. 11. Current or past: (a) medical (psychiatric, non-psychiatric) condition, disease, disorder, injury, or disability\*; or (b) non-medical situation or circumstance that, in the opinion of the Site PI, study participation: 1. may pose a significant or undue risk to the person; 2. make it unlikely the person will complete all the study requirements per protocol; or 3. may adversely impact the integrity of the data or the validity of the study results. \[\*Examples include, but are not limited to, the following types of conditions, diseases or disorders: renal insufficiency or failure, vascular disease, unstable or concerning cardiac disease, endocrinologic concerns (e.g., poorly controlled diabetes), immunosuppression, respiratory issues, psychiatric (e.g., schizophrenia), neurologic (e.g., cognitive, seizure), sickle cell disease, lupus, clotting disorders, active neoplastic disease (excluding basal or squamous cell carcinoma of the skin with intent for curative excision), recent documented history (within the last 3 months) of dysphagia or aspiration difficulty\] 12. Is female and lactating, pregnant, or plans to become pregnant during the study. Participants of child-bearing potential that are sexually active must use a reliable form of birth control. Acceptable birth control methods: (a) sterilization surgery for women, (b) surgical sterilization implant for women, (c) sterilization surgery for men (including all male partners), (d) Long-acting reversible contraceptives (LARC)-implantable rod and Intrauterine Device (IUD), (e) contraceptive shots/injection every 3 months, (f) oral contraceptives (pills), (g) contraceptive patch, (h) vaginal contraceptive ring, and (i) complete abstinence. 13. Abusive use of alcohol or drugs that could interfere with participation, as determined by the Site PI. 14. Concurrently participating in another interventional clinical study. 15. Requires or plans the use of diathermy, transcranial magnetic stimulation, or electroconvulsive therapy (ECT) during the course of the study. 16. Is known to be under incarceration or legal detention as determined by the Site PI. 17. Non-English speaking, unless the enrolling site has an IRB-approved translated consent and qualified medical interpreter resources available in the participant's language to support all study visits and procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ReWire System Safety | From device implantation to up to 2 years following implantation. | Safety of the ReWire system will be assessed by documenting the nature, frequency, severity, and relatedness of adverse events associated with the device, including those attributable to device implantation, stimulation delivery, and rehabilitation procedures. |
| ReWire System Feasibility | All visits after implantation, up to approximately 26 weeks post-enrollment. | Feasibility of the ReWire system will be assessed by the proportion of successful stimulation triggering events recorded in the ReWire System log during therapy sessions. The system will be considered feasible if \>50% of valid trigger attempts result in successful stimulation delivery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 6 Meter Walk Test (6MWT) | At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment. | This measure assesses gait endurance by measuring the distance walked in 6 minutes along a hallway. Determine whether CLV improves six-minute walking test (6MWT) score compared to baseline. This measure is not a scale. Higher distance covered is better. |
| 10 Meter Walk Test (10MWT) | At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment. | This measure assesses walking speed (meter/second) over a short distance. Determine whether CLV improves 10-Meter Walk Test (10-MWT) score compared to baseline. This measure is not a scale. Lower time to complete is better. |
| Timed Up-and Go (TUG)Test | At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment. | This measure assesses the functional mobility and fall risk by timing participants as they stand from a seated position, walk to a set point, and return to sit. Determine whether CLV improves Timed Up-and Go (TUG)Test score compared to baseline. This measure is not a scale. Lower time to complete is better. |
| Walking Index for Spinal Cord Injury II (WISCI II) | At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment. | This measure assesses the type and amount of assistance required for walking. Determine whether CLV improves Walking Index for Spinal Cord Injury II (WISCI II) score compared to baseline. This scale is from 0-20. Higher scores indicate better walking performance. |
| Lower Extremity Motor Score (LEMS) | At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment. | This measure quantifies the strength of five key muscle groups in each lower extremity. Determine whether CLV improves Lower Extremity Motor Score (LEMS) compared to baseline. This scale is from 0 to 50. Higher scores are better. |
| SCI-Functional Independence Scale - Ambulation Subsection (SCI-FIS) | At baseline (screening), after implantation, week 14 (double-blind phase), week 22 (Open-label phase) and week 26 (1 month follow-up). | This measure assesses self-perceived limitations with walking and basic mobility. This scale is from 0-24. Higher scores indicate better function. |
| SCI Independence Measure (SCIM) III | At baseline (screening), after implantation, week 14 (double-blind phase), week 22 (Open-label phase) and week 26 (1 month follow-up). | This measure assesses the functional independence (ability to safely perform daily activities without physical or cognitive assistance). This scale is from 0-100. Higher scores indicate greater independence. |
| International SCI Pain Basic Data Set | At baseline (screening), after implantation, week 14 (double-blind phase), week 22 (Open-label phase) and week 26 (1 month follow-up). | This measure is not a scale. It is a questionnaire consisting of items regarding overall pain and items regarding each of the three worst pain problems (assesses pain intensity and classification for each specific pain) in SCI patients. |
| Observed Functional Change Assessment (OFCA) | At baseline (screening) and all visits after implantation, up to approximately 26 weeks post-enrollment. | This measure is not a scale. It captures participants' reports/observations of positive functional changes (captures emergent functional gains-such as the appearance of new voluntary activation or task initiation-that may not yet be reflected in the numerical thresholds of standardized, performance-based scales). |
| Participant Satisfaction Survey | At week 14 (double-blind phase), week 22 (Open-label phase) and week 26 (1 month follow-up). | This measure collects participant-reported feedback regarding usability, tolerability, and overall experience with CLV therapy. |
| Participant Blinding Questionnaire | At week 14 (double-blind phase). | This measure is not a scale. It assesses effectiveness of blinding from the participant perspective. |
| Therapist Blinding Questionnaire | At week 14 (double-blind phase). | This measure is not a scale. It assesses effectiveness of blinding from the treating therapist perspective. |
Countries
United States
Contacts
CONTACTAmy Porter
PRINCIPAL_INVESTIGATORRobert Rennaker, PhD
The University of Texas at Dallas
PRINCIPAL_INVESTIGATORJane Wigginton, MD
The University of Texas at Dallas
PRINCIPAL_INVESTIGATORSeth Hays, PhD
The University of Texas at Dallas
PRINCIPAL_INVESTIGATORRita Hamilton, DO
Baylor University Medical Center (BUMC)
PRINCIPAL_INVESTIGATORChad Swank, PhD
Spaulding Rehabilitation Hospital, Mass General Brigham
PRINCIPAL_INVESTIGATORMichael Foreman, MD
Urgent Surgery Associates, PA
Outcome results
None listed