Ignite Creation Date:
2024-10-26 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 3:39 PM
Study NCT ID:
NCT06587841
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-29
Brief Title:
Noninvasive Spinal Cord Stimulation for Early SCI
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Noninvasive Spinal Cord Neuromodulation to Improve Lower Urinary Tract Function After Spinal Cord Injury in Ukrainian War Veterans
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The investigators are looking to determine the safety and efficacy of non-invasive transcutaneous spinal cord stimulation TSCS in promoting recovery of lower urinary tract LUT bowel sexual and cardiovascular function as well as spasticity in individuals with subacute SCI time since injury 3-6 months and the impact on quality of life The study will be conducted at two sites site 1 in Canada and site 2 in the Ukraine Up to 60 subjects will be enrolled 10 adults at the ICORD University of British Columbia UBC Vancouver Canada site and 50 adults at the Rivne Regional War Veterans Hospital Rivne Ukraine Eligible participants will be randomized 11 ratio either to Group 1 G1 or Group 2 G2 G1 will receive therapeutic TSCS for 8 weeks 3 times per week 1 hour per session in conjunction with conventional rehabilitation 3-4 hours per day 5 days per week G2 will receive 8 weeks of sham stimulation in conjunction with conventional rehabilitation After 8 weeks G2 will cross over and receive therapeutic TSCS for 8 weeks whereas G1 will continue to receive TSCS therapy for another 8 weeks for a total of 16 weeks Eligible participants enrolled into the study will attend fifty eight 58 visits for assessments therapy and follow-up The expected duration of study participation for each participant will be 33 weeks
Detailed Description:
PURPOSE
The purpose of this clinical study is to investigate the safety and effectiveness of non-surgical transcutaneous spinal cord stimulation TSCS in helping with recovery of bladder function in individuals with SCI Assessments The immediate effects of TSCS ie effects with stimulation on long-term effects of TSCS and the persisting effects of TSCS ie any changes in function that are still present with stimulation off after several weeks of using the stimulation regularly -pre versus post study comparison This is a Phase II study A Phase II study is undertaken after preliminary safety testing for a treatment
Investigational Study Device
The SCONE Spinal COrd NEuromodulation class II investigational device is a non-invasive central nervous system CNS stimulator electrical continence device designed to provide TSCS for the improvement of symptoms of bladder dysfunction associated with centrally-mediated NLUTD
The SCONE devices primary mechanism of action is electrical stimulation delivered to the spinal cord through the skin The device consists of an electrode connected by an electrical cable to a battery-powered pulse source and uses advanced waveforms to deliver electrical stimulation directly to the spinal cord neural networks associated with pelvic floor function with the aim to activate and retrain the neural circuits responsible for urinary bladder control
Primary Objective
To assess the effect of non-invasive TSCS on LUT function in people with sub-acute SCI following eight weeks of therapy in comparison to inactive sham control
Secondary and Ancillary Objectives
To assess the effect of non-invasive TSCS on bowel dysfunction sexual dysfunctions cardiovascular function spasticity and quality of life
Specific Aim 1 - TSCS Mapping To establish function-specific TSCS parameters and electrode placement to activate spinal neural circuits controlling LUT function in individuals with sub-acute SCI
Primary Outcomes Motor threshold TSCS parameters based on surface EMG for skeletal muscles innervated by motor neurons localized in the same spinal cord segments as neural circuits controlling LUT function surface EMG of the EAS surrogate for EUS
Hypothesis In light of recent findings on the efficacy of spinal cord stimulation to improve LUT function the optimal parameters for EMG responses ie mapping will be revealed during TSCS
Specific Aim 2 -Effect of Real-Time TSCS To test the safety and efficacy of real-time TSCS in improving LUT function in individuals with sub-acute SCI
Primary Outcomes Voiding efficiency of the bladder surface EMG of the EAS surrogate EUS continuous cardiovascular monitoring for TSCS-dependent changes in BP ie adverse cardiovascular events such as AD
Hypothesis The investigators hypothesize that acute TSCS will reproducibly and safely improve voiding and storage functions in LUT and elicit pelvic floor EMG without any cardiovascular adverse events
Specific Aim 3 - Effect of Long-Term TSCS To investigate the efficacy of long-term TSCS in mitigating the NLUTD in the sub-acute period following SCI
Primary Outcomes Neurogenic Bladder Symptom Score NBSS Secondary outcomes UDI and TNFBM Ancillary Outcomes Neurogenic Bowel Dysfunction NBD Score sexual function screening tool Sexual Health Inventory for Men SHIM Questionnaire IIEF FSFI FSDS 24hr ABPM International Standards for Neurological Classification of SCI ISNCSCI Patient Health Questionnaire -9 PHQ-9 PTSD Checklist for DSM-5 PCL-5 WHO Quality of Life-BREF WHOQOL-BREF and modified Ashworth Score MAS Outcomes will be performed at baseline 8- and 16-weeks post TSCS Follow-up assessments will be performed 8 weeks after cessation of treatment to assess the persisting effects of TCS
Hypothesis Long-term TSCS will promote bladderbowel voiding and storage functions as well as improvements in sexual function
Specific Aim 4 - Effect of Delayed Onset TSCS To investigate the efficacy of delayed long-term TSCS in mitigating NLUTD in the sub-acute period following SCI
Primary Outcomes NBSS Secondary Outcomes UDI and TNFBM Ancillary Outcomes NBD Score sexual function screening tool SHIM Questionnaire IIEF FSFI FSDS 24hr ABPM ISNCSCI PHQ-9 PCL-5 WHOQOL-BREF and MAS Outcomes will be performed at baseline 8 weeks sham and 16 weeks after 8 weeks of TSCS therapy Follow-up assessments will be performed after cessation of TCS to assess the persisting effects of TSCS
Hypothesis Based on our promising preliminary findings in chronic SCI the investigators hypothesize that even with delayed onset TSCS will promote bladderbowel voiding and storage functions as well as boost sexual function
Primary Efficacy Endpoint Reduction in NBSS score by 10 points at 8 weeks of therapy
Secondary Efficacy Endpoint Mean improvement in voiding efficiency by at least 50 Mean reduction in TNFBM by at least 50
RESEARCH DESIGN
Overall Research Design
The study will include sixty adults 19 - 65 years n50 in Ukraine and n10 in Canada with a sub-acute time since injury of 3-6 months motor-complete SCI ASIA Impairment Scale AIS A or B at spinal segments C5-T10 with documented impaired bladder function The expected duration of study participation for each participant will be 33 weeks Eligible Canadian participants enrolled into the study will attend 58 visits at ICORD
Detailed Research Design
The investigators propose a phase II randomized single-blinded sham-controlled clinical trial to examine the effect of non-invasive TCS on LUT function in people with SCI The investigators will include sixty adults 19 - 65 years n50 in Ukraine and n10 in Canada with a sub-acute time since injury of 3-6 months motor-complete SCI AIS A or B at spinal cord segments C5-T10 with documented impaired LUT function Individuals with SCI will be recruited at Rivne Regional War Veterans Hospital for the Ukrainian site and at ICORD for the Canadian site The rationale for including the Canadian cohort n10 is to control for the environmental impact such as potential differences in intensity of sub-acute rehabilitation and severity of war-related psychological impact on functional recovery Furthermore participants will be instructed to adhere to established bowel and LUT routines and refrain from initiation of new medications for bowel and LUT management without notifying the Principal Investigator of this study
Secondary and ancillary outcomes will include assessments of bowel function sexual functions cardiovascular function and spasticity Group 1 G1 n25 in Ukraine and n5 in Canada will receive therapeutic TSCS for 8 weeks 3 times per week 1 hour per session in conjunction with conventional rehabilitation 3-4 hours per day 5 days per week G2 n25 in Ukraine and n5 in Canada will receive 8 weeks of sham stimulation in conjunction with conventional rehabilitation After 8 weeks G2 will switch to therapeutic TSCS for 8 weeks ie delayed onset of TSCS G1 will continue to receive TSCS therapy for another 8 weeks for a total of 16 weeks
STATISTICAL PLAN DATA ANALYSIS
Short term changes in voiding efficiency and BP will be analyzed using paired t-tests Aim 2 Primary and secondary outcome responder rates ie proportion of participants realizing 10-point improvement from baseline in NBSS 50 improvement in voiding efficiency 50 reduction in TNFBM will be analyzed using logistic regression Aims 3 and 4 Primary secondary and ancillary outcomes will also be analyzed directly using mixed effects repeated measures models including fixed effects for treatment arm and country and a random effect to account for nonindependence of repeated measurements within participants Treatment-arm specific 95 confidence intervals will be constructed for all outcomes Logistic mixed effect models and analysis of variance ANOVA for short term changes in voiding efficiency and BP will also incorporate interaction terms to examine differential effects associated with Ukraine-based vs Canada-based participants Since the study is not powered for this assessment interaction p020 will be taken as evidence of possible differential effects and analyses limited to Ukraine-based participants only will be conducted separately Interaction terms will also be included in mixed effects models to examine differential time trends between treatment arms baseline to 8-week and 8-week to 16-week Sham group 16-week outcomes will also be compared to experimental group 8-week outcomes both having undergone 8 weeks of therapy to that point Data transformations or nonparametric methods eg Wilcoxon signed-rank test for paired data Friedman test for nonparametric repeated measures will be substituted in cases where distributional assumptions are not met Analyses will include all participants completing each phase of the study sensitivity analyses and multiple imputation will also be conducted as appropriate to examine the possible impact of attrition which is expected to be low in this inpatient study Analyses will not be corrected for multiple comparisons in view of the exploratory nature of many of the other outcomes
The purpose of this clinical study is to investigate the safety and effectiveness of non-surgical transcutaneous spinal cord stimulation TSCS in helping with recovery of bladder function in individuals with SCI Assessments The immediate effects of TSCS ie effects with stimulation on long-term effects of TSCS and the persisting effects of TSCS ie any changes in function that are still present with stimulation off after several weeks of using the stimulation regularly -pre versus post study comparison This is a Phase II study A Phase II study is undertaken after preliminary safety testing for a treatment
Investigational Study Device
The SCONE Spinal COrd NEuromodulation class II investigational device is a non-invasive central nervous system CNS stimulator electrical continence device designed to provide TSCS for the improvement of symptoms of bladder dysfunction associated with centrally-mediated NLUTD
The SCONE devices primary mechanism of action is electrical stimulation delivered to the spinal cord through the skin The device consists of an electrode connected by an electrical cable to a battery-powered pulse source and uses advanced waveforms to deliver electrical stimulation directly to the spinal cord neural networks associated with pelvic floor function with the aim to activate and retrain the neural circuits responsible for urinary bladder control
Primary Objective
To assess the effect of non-invasive TSCS on LUT function in people with sub-acute SCI following eight weeks of therapy in comparison to inactive sham control
Secondary and Ancillary Objectives
To assess the effect of non-invasive TSCS on bowel dysfunction sexual dysfunctions cardiovascular function spasticity and quality of life
Specific Aim 1 - TSCS Mapping To establish function-specific TSCS parameters and electrode placement to activate spinal neural circuits controlling LUT function in individuals with sub-acute SCI
Primary Outcomes Motor threshold TSCS parameters based on surface EMG for skeletal muscles innervated by motor neurons localized in the same spinal cord segments as neural circuits controlling LUT function surface EMG of the EAS surrogate for EUS
Hypothesis In light of recent findings on the efficacy of spinal cord stimulation to improve LUT function the optimal parameters for EMG responses ie mapping will be revealed during TSCS
Specific Aim 2 -Effect of Real-Time TSCS To test the safety and efficacy of real-time TSCS in improving LUT function in individuals with sub-acute SCI
Primary Outcomes Voiding efficiency of the bladder surface EMG of the EAS surrogate EUS continuous cardiovascular monitoring for TSCS-dependent changes in BP ie adverse cardiovascular events such as AD
Hypothesis The investigators hypothesize that acute TSCS will reproducibly and safely improve voiding and storage functions in LUT and elicit pelvic floor EMG without any cardiovascular adverse events
Specific Aim 3 - Effect of Long-Term TSCS To investigate the efficacy of long-term TSCS in mitigating the NLUTD in the sub-acute period following SCI
Primary Outcomes Neurogenic Bladder Symptom Score NBSS Secondary outcomes UDI and TNFBM Ancillary Outcomes Neurogenic Bowel Dysfunction NBD Score sexual function screening tool Sexual Health Inventory for Men SHIM Questionnaire IIEF FSFI FSDS 24hr ABPM International Standards for Neurological Classification of SCI ISNCSCI Patient Health Questionnaire -9 PHQ-9 PTSD Checklist for DSM-5 PCL-5 WHO Quality of Life-BREF WHOQOL-BREF and modified Ashworth Score MAS Outcomes will be performed at baseline 8- and 16-weeks post TSCS Follow-up assessments will be performed 8 weeks after cessation of treatment to assess the persisting effects of TCS
Hypothesis Long-term TSCS will promote bladderbowel voiding and storage functions as well as improvements in sexual function
Specific Aim 4 - Effect of Delayed Onset TSCS To investigate the efficacy of delayed long-term TSCS in mitigating NLUTD in the sub-acute period following SCI
Primary Outcomes NBSS Secondary Outcomes UDI and TNFBM Ancillary Outcomes NBD Score sexual function screening tool SHIM Questionnaire IIEF FSFI FSDS 24hr ABPM ISNCSCI PHQ-9 PCL-5 WHOQOL-BREF and MAS Outcomes will be performed at baseline 8 weeks sham and 16 weeks after 8 weeks of TSCS therapy Follow-up assessments will be performed after cessation of TCS to assess the persisting effects of TSCS
Hypothesis Based on our promising preliminary findings in chronic SCI the investigators hypothesize that even with delayed onset TSCS will promote bladderbowel voiding and storage functions as well as boost sexual function
Primary Efficacy Endpoint Reduction in NBSS score by 10 points at 8 weeks of therapy
Secondary Efficacy Endpoint Mean improvement in voiding efficiency by at least 50 Mean reduction in TNFBM by at least 50
RESEARCH DESIGN
Overall Research Design
The study will include sixty adults 19 - 65 years n50 in Ukraine and n10 in Canada with a sub-acute time since injury of 3-6 months motor-complete SCI ASIA Impairment Scale AIS A or B at spinal segments C5-T10 with documented impaired bladder function The expected duration of study participation for each participant will be 33 weeks Eligible Canadian participants enrolled into the study will attend 58 visits at ICORD
Detailed Research Design
The investigators propose a phase II randomized single-blinded sham-controlled clinical trial to examine the effect of non-invasive TCS on LUT function in people with SCI The investigators will include sixty adults 19 - 65 years n50 in Ukraine and n10 in Canada with a sub-acute time since injury of 3-6 months motor-complete SCI AIS A or B at spinal cord segments C5-T10 with documented impaired LUT function Individuals with SCI will be recruited at Rivne Regional War Veterans Hospital for the Ukrainian site and at ICORD for the Canadian site The rationale for including the Canadian cohort n10 is to control for the environmental impact such as potential differences in intensity of sub-acute rehabilitation and severity of war-related psychological impact on functional recovery Furthermore participants will be instructed to adhere to established bowel and LUT routines and refrain from initiation of new medications for bowel and LUT management without notifying the Principal Investigator of this study
Secondary and ancillary outcomes will include assessments of bowel function sexual functions cardiovascular function and spasticity Group 1 G1 n25 in Ukraine and n5 in Canada will receive therapeutic TSCS for 8 weeks 3 times per week 1 hour per session in conjunction with conventional rehabilitation 3-4 hours per day 5 days per week G2 n25 in Ukraine and n5 in Canada will receive 8 weeks of sham stimulation in conjunction with conventional rehabilitation After 8 weeks G2 will switch to therapeutic TSCS for 8 weeks ie delayed onset of TSCS G1 will continue to receive TSCS therapy for another 8 weeks for a total of 16 weeks
STATISTICAL PLAN DATA ANALYSIS
Short term changes in voiding efficiency and BP will be analyzed using paired t-tests Aim 2 Primary and secondary outcome responder rates ie proportion of participants realizing 10-point improvement from baseline in NBSS 50 improvement in voiding efficiency 50 reduction in TNFBM will be analyzed using logistic regression Aims 3 and 4 Primary secondary and ancillary outcomes will also be analyzed directly using mixed effects repeated measures models including fixed effects for treatment arm and country and a random effect to account for nonindependence of repeated measurements within participants Treatment-arm specific 95 confidence intervals will be constructed for all outcomes Logistic mixed effect models and analysis of variance ANOVA for short term changes in voiding efficiency and BP will also incorporate interaction terms to examine differential effects associated with Ukraine-based vs Canada-based participants Since the study is not powered for this assessment interaction p020 will be taken as evidence of possible differential effects and analyses limited to Ukraine-based participants only will be conducted separately Interaction terms will also be included in mixed effects models to examine differential time trends between treatment arms baseline to 8-week and 8-week to 16-week Sham group 16-week outcomes will also be compared to experimental group 8-week outcomes both having undergone 8 weeks of therapy to that point Data transformations or nonparametric methods eg Wilcoxon signed-rank test for paired data Friedman test for nonparametric repeated measures will be substituted in cases where distributional assumptions are not met Analyses will include all participants completing each phase of the study sensitivity analyses and multiple imputation will also be conducted as appropriate to examine the possible impact of attrition which is expected to be low in this inpatient study Analyses will not be corrected for multiple comparisons in view of the exploratory nature of many of the other outcomes
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None