Ignite Creation Date:
2024-07-17 @ 11:45 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06463418
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-08
First Post:
2024-05-22
Brief Title:
Exoskeleton Training for Spinal Cord Injury Neuropathic Pain ExSCIP
Sponsor:
University College Dublin
Organization:
University College Dublin
Study Overview
Official Title:
Exoskeleton Training for Spinal Cord Injury Neuropathic Pain ExSCIP Protocol for a Phase 2 Feasibility Randomised Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ExSCIP
Brief Summary:
The goal of this feasibility trial is to learn if exoskeleton or robotic walking works to reduce nerve neuropathic pain after spinal cord injury
This study asks is
Providing walking practice through use of a robotic device exoskeleton three times per week for twelve weeks possible to deliver
Would people sign up and stick to the programme
And will it help to reduce neuropathic pain levels after spinal injury
Researchers will compare robotic walking and a relaxation program to see if robotic walking works to reduce neuropathic pain levels after spinal injury
Participants will
Complete a number of questionnaires and tests related to their pain before the trial
Complete robotic walking or a relaxation program three times per week for twelve weeks
Complete the same questionnaires and tests after the trial finishes and 6 months after
Complete an interview telling researchers about their experiences of the trial
This study asks is
Providing walking practice through use of a robotic device exoskeleton three times per week for twelve weeks possible to deliver
Would people sign up and stick to the programme
And will it help to reduce neuropathic pain levels after spinal injury
Researchers will compare robotic walking and a relaxation program to see if robotic walking works to reduce neuropathic pain levels after spinal injury
Participants will
Complete a number of questionnaires and tests related to their pain before the trial
Complete robotic walking or a relaxation program three times per week for twelve weeks
Complete the same questionnaires and tests after the trial finishes and 6 months after
Complete an interview telling researchers about their experiences of the trial
Detailed Description:
Background and Rationale
Following SCI approximately 53 of people develop neuropathic pain NP Irish SCI data identifies high pain intensity and pain interference levels with NP and significantly poorer quality of life QoL than other pain phenotypes Individuals can describe NP as more debilitating than the other consequences of SCI as their most persistent health issue and adequate pain relief as an unmet need
International data identify the proportional burden of NP following SCI as significant Ninety-four percent of individuals are prescribed 1 medication the mean number of physician office visits in a 6-month period due to SCI NP is reported as 2 and the total annualised cost of NP per subject in the United States US is reported as 26270 direct 8636 indirect 17634
The presence of pain is further associated with lower return to work rates following injury and more than a third of individuals with SCI in employment report frequent pain interference with their work Pain interference with function health status and work are noted to be significantly worse in individuals with more severe NP where overall work impairment is reported at 38
NP after SCI is multi-faceted and heterogenous making isolation of specific mechanisms more challenging Mechanisms hypothesised for NP after SCI include neuronal hyperexcitability central and peripheral sensitisation and corticothalamic maladaptive neuroplasticity Additionally NP symptom severity post SCI has been reported to be associated with a combination of residual spinothalamic tract STT function below the level of injury and with catastrophising pain coping mechanisms
The mechanistic effects of sensorimotor stimulation on NP stem from Phantom Limb Pain research PLP with significant reversal of cortical dysfunction in the primary somatosensory cortex of individuals with PLP evident Similar maladaptive cortical reorganisation is hypothesised to be associated with NP in SCI
This is further supported by data garnered from electroencephalography EEG studies showing that changes in oscillatory brain activity known as thalamo-cortical dysrhythmia are associated with the presence of NP NP in SCI is associated with an EEG power signal increase in the theta band and possibly high beta band but a decrease in the high-alpha-low-beta band In addition NP in SCI is associated with decreased reactivity of alpha band power signals in response to eye opening Thus it has applications as a biomarker for current NP and as a predictor of development of future NP
The mainstay of NP treatment after SCI is pharmacotherapy with anticonvulsants and antidepressants to reduce pain intensity Pregabalingabapentin duloxetine amitriptyline andor opioids are the first- and second-line treatments recommended although severe pain remains refractory to these treatments in 23 of sufferers Survey data report high use of non-steroidal anti-inflammatories and paracetamol
Significant side-effects of medications are reported SCI patients are particularly prone to central nervous system related side effects which are often intolerable These together with fear of medication dependency result in poor adherence to pharmacological regimens leading to a call for non-pharmacological treatment options for people with NP after SCI
Virtual reality immersive virtual walking virtual illusionimagined walking has shown promise for reducing NP intensity and interference after SCI Virtual illusion interventions show evidence of direct and corrective stimulation to the reorganised sensorimotor areas in SCI patients with NP supporting the theory that NP mechanisms are reversible However actual sensorimotor intervention studies are inconclusive in SCI at this point with limited focus on walking despite compelling preclinical studies showing prevention andor reversal of SCI neuropathic pain Notably in animal studies other exercise paradigms including swimming and stance training had only transient or no effects on SCI-induced NP suggesting that the rhythmic stimulation of proprioceptive and mechanosensory afferents together with weight bearing experienced in walking might be necessary to reduce NP
The exoskeleton intervention itself is not new within the neurorehabilitation space for SCI However no RCTs to date have specifically recruited participants with moderate-to-severe NP in order to assess its mechanistic effects on NP The ExSCIP randomised feasibility trial addresses this current knowledge gap examining exoskeleton-based walking 3 times per week as a mechanistic-based intervention for NP after SCI It will test the feasibility and acceptability of an exoskeleton and whether it demonstrates positive signals in reduction of NP intensity and interference levels to warrant onward progression to a definitive trial
Aims and Objectives
The overall aim of this study is to examine the feasibility and acceptability of an exoskeleton mechanistic-targeted walking intervention for NP in people with SCI
The primary objectives for the study are
1 Implement an exoskeleton training programme for people with below level NP 6 months after a traumatic SCI
2 Pilot and assess the impact of an exoskeleton-based walking intervention in NP 6 months after SCI examining feasibility outcomes and short and long-term 6 months changes in pain intensity and pain interference
The ExSCIP study is a phase 2 randomised single blinded feasibility trial with the aim of examining progression criteria for a definitive trial
Progression criteria are based on consideration of the primary objectives around feasibility and the potential for effectiveness and implementation in clinical practice Quantitative and qualitative process evaluation data will be analysed to consider the following continuation criteria
Successful uptake recruitment and retention
Successful implementation of the ExSCIP intervention
Process evaluation indicates that ExSCIP is acceptable to people with NP after SCI and to staff delivering the intervention
A positive effect on pain and pain interference outcomes are identified and are meaningful
Cost analysis indicates that the ExSCIP intervention might be cost effective The intervention will be delivered in the Motion Analysis Laboratory at University College Dublin UCD
Participant Screening
Stage 1 Phone Screening
NP will be screened for as a minimum criterion initially by phone This phone screening will do the following
Confirm their SCI diagnosis eg traumatic aetiology and 6 months post injury
Confirm they are on a stable medication regimen
Confirm they are exoskeleton naïve
Screen for the presence of NP using the Spinal Cord Injury Pain Instrument SCIPI
Inquire into anthropometric details eg the candidates height and weight to give further indication relating to their potential suitabilitycompatibility with the exoskeleton
Once the phone screening has been completed candidates deemed to be potentially suitable to participate in the trial will be booked in for an in-person assessment Potential participants will be provided with a study information leaflet at this point and informed consent will be sought from participants to complete an in-person assessment A 1 week grace period will be given to participants between provision of the study information leaflet and obtaining informed consent
Stage 2 In-Person Assessment
An in-person assessment to confirm participant suitability will be performed by an independent assessor The assessment will entail the following steps
Confirmation of presence of moderate to severe below level NP
NP will be confirmed based on a neurological examination a score of 4 on the Douleur Neuropathique 4 DN4 and a comprehensive pain history
This will be supported by the use of the ISCIP Pain Classification
Moderate and severe NP as confirmed above will be described as pain 3 and 6 on the 0-10 Numerical Rating Scale NRS for NP averaged over a week
Anthropometric and clinical assessment for compatibility for use of exoskeleton
- Participants will undergo an anthropometric assessment to ensure no height weight joint range of movement or muscle spasticity restrictions to exoskeleton use apply
Stage 3 Informed consent and data collection
Candidates who meet inclusion criteria will be provided with a study information leaflet see Figure 2 and asked to provide written informed consent that they agree to participate in the study via a consent form
The independent assessor will then collect data at baseline for the outcome measures outlined Please refer to outcomes section for full details
Datastatistical analysis
Descriptive statistics and estimation using 95 CIs will be the main focus of the analysis The number of participants recruited and retained and information on missing or incomplete data from all outcome measures will be explored Baseline demographics and outcome variables will be compared at all assessment times within groups
For categorical measures frequencies and percentages will be presented and for continuous measures the mean and standard deviation SD will be reported For continuous measures which show evidence of some skew a median and interquartile range may also be presented or substituted for the mean and SD Within group change scores and their 95 CI will be examined in relation to the MCID Repeated measures ANOVAs will be used to compare between group differences of continuous variables across the three time points Statistical significance will be determined α-priori at an alpha level of 005
For analysis of EEG data this will be an exploratory analysis using a multilevel linear mixed model LMM approach to examine differences between the intervention groups over time in the EEG alpha beta and theta band power Repeated measures within participants will be modelled as a random effect Fixed effects in the model will include group assignment and time The moderating effects of pain intensity and interference will also be evaluated The LMM will study both main effects and interaction effects using the R package lme4 to fit the models Models will be compared using Likelihood Ratio Tests LRT to assess the significance of effects Statistical significance will be determined α-priori at an alpha level of 005
When all data is collected data analysis will be conducted by a data processor blinded to group allocation A full statistical analysis plan will be prepared prior to final analysis Statistical analysis will be conducted using SPSS version 29 software and analysis will be conducted as intention to treat ITT and per protocol
Following SCI approximately 53 of people develop neuropathic pain NP Irish SCI data identifies high pain intensity and pain interference levels with NP and significantly poorer quality of life QoL than other pain phenotypes Individuals can describe NP as more debilitating than the other consequences of SCI as their most persistent health issue and adequate pain relief as an unmet need
International data identify the proportional burden of NP following SCI as significant Ninety-four percent of individuals are prescribed 1 medication the mean number of physician office visits in a 6-month period due to SCI NP is reported as 2 and the total annualised cost of NP per subject in the United States US is reported as 26270 direct 8636 indirect 17634
The presence of pain is further associated with lower return to work rates following injury and more than a third of individuals with SCI in employment report frequent pain interference with their work Pain interference with function health status and work are noted to be significantly worse in individuals with more severe NP where overall work impairment is reported at 38
NP after SCI is multi-faceted and heterogenous making isolation of specific mechanisms more challenging Mechanisms hypothesised for NP after SCI include neuronal hyperexcitability central and peripheral sensitisation and corticothalamic maladaptive neuroplasticity Additionally NP symptom severity post SCI has been reported to be associated with a combination of residual spinothalamic tract STT function below the level of injury and with catastrophising pain coping mechanisms
The mechanistic effects of sensorimotor stimulation on NP stem from Phantom Limb Pain research PLP with significant reversal of cortical dysfunction in the primary somatosensory cortex of individuals with PLP evident Similar maladaptive cortical reorganisation is hypothesised to be associated with NP in SCI
This is further supported by data garnered from electroencephalography EEG studies showing that changes in oscillatory brain activity known as thalamo-cortical dysrhythmia are associated with the presence of NP NP in SCI is associated with an EEG power signal increase in the theta band and possibly high beta band but a decrease in the high-alpha-low-beta band In addition NP in SCI is associated with decreased reactivity of alpha band power signals in response to eye opening Thus it has applications as a biomarker for current NP and as a predictor of development of future NP
The mainstay of NP treatment after SCI is pharmacotherapy with anticonvulsants and antidepressants to reduce pain intensity Pregabalingabapentin duloxetine amitriptyline andor opioids are the first- and second-line treatments recommended although severe pain remains refractory to these treatments in 23 of sufferers Survey data report high use of non-steroidal anti-inflammatories and paracetamol
Significant side-effects of medications are reported SCI patients are particularly prone to central nervous system related side effects which are often intolerable These together with fear of medication dependency result in poor adherence to pharmacological regimens leading to a call for non-pharmacological treatment options for people with NP after SCI
Virtual reality immersive virtual walking virtual illusionimagined walking has shown promise for reducing NP intensity and interference after SCI Virtual illusion interventions show evidence of direct and corrective stimulation to the reorganised sensorimotor areas in SCI patients with NP supporting the theory that NP mechanisms are reversible However actual sensorimotor intervention studies are inconclusive in SCI at this point with limited focus on walking despite compelling preclinical studies showing prevention andor reversal of SCI neuropathic pain Notably in animal studies other exercise paradigms including swimming and stance training had only transient or no effects on SCI-induced NP suggesting that the rhythmic stimulation of proprioceptive and mechanosensory afferents together with weight bearing experienced in walking might be necessary to reduce NP
The exoskeleton intervention itself is not new within the neurorehabilitation space for SCI However no RCTs to date have specifically recruited participants with moderate-to-severe NP in order to assess its mechanistic effects on NP The ExSCIP randomised feasibility trial addresses this current knowledge gap examining exoskeleton-based walking 3 times per week as a mechanistic-based intervention for NP after SCI It will test the feasibility and acceptability of an exoskeleton and whether it demonstrates positive signals in reduction of NP intensity and interference levels to warrant onward progression to a definitive trial
Aims and Objectives
The overall aim of this study is to examine the feasibility and acceptability of an exoskeleton mechanistic-targeted walking intervention for NP in people with SCI
The primary objectives for the study are
1 Implement an exoskeleton training programme for people with below level NP 6 months after a traumatic SCI
2 Pilot and assess the impact of an exoskeleton-based walking intervention in NP 6 months after SCI examining feasibility outcomes and short and long-term 6 months changes in pain intensity and pain interference
The ExSCIP study is a phase 2 randomised single blinded feasibility trial with the aim of examining progression criteria for a definitive trial
Progression criteria are based on consideration of the primary objectives around feasibility and the potential for effectiveness and implementation in clinical practice Quantitative and qualitative process evaluation data will be analysed to consider the following continuation criteria
Successful uptake recruitment and retention
Successful implementation of the ExSCIP intervention
Process evaluation indicates that ExSCIP is acceptable to people with NP after SCI and to staff delivering the intervention
A positive effect on pain and pain interference outcomes are identified and are meaningful
Cost analysis indicates that the ExSCIP intervention might be cost effective The intervention will be delivered in the Motion Analysis Laboratory at University College Dublin UCD
Participant Screening
Stage 1 Phone Screening
NP will be screened for as a minimum criterion initially by phone This phone screening will do the following
Confirm their SCI diagnosis eg traumatic aetiology and 6 months post injury
Confirm they are on a stable medication regimen
Confirm they are exoskeleton naïve
Screen for the presence of NP using the Spinal Cord Injury Pain Instrument SCIPI
Inquire into anthropometric details eg the candidates height and weight to give further indication relating to their potential suitabilitycompatibility with the exoskeleton
Once the phone screening has been completed candidates deemed to be potentially suitable to participate in the trial will be booked in for an in-person assessment Potential participants will be provided with a study information leaflet at this point and informed consent will be sought from participants to complete an in-person assessment A 1 week grace period will be given to participants between provision of the study information leaflet and obtaining informed consent
Stage 2 In-Person Assessment
An in-person assessment to confirm participant suitability will be performed by an independent assessor The assessment will entail the following steps
Confirmation of presence of moderate to severe below level NP
NP will be confirmed based on a neurological examination a score of 4 on the Douleur Neuropathique 4 DN4 and a comprehensive pain history
This will be supported by the use of the ISCIP Pain Classification
Moderate and severe NP as confirmed above will be described as pain 3 and 6 on the 0-10 Numerical Rating Scale NRS for NP averaged over a week
Anthropometric and clinical assessment for compatibility for use of exoskeleton
- Participants will undergo an anthropometric assessment to ensure no height weight joint range of movement or muscle spasticity restrictions to exoskeleton use apply
Stage 3 Informed consent and data collection
Candidates who meet inclusion criteria will be provided with a study information leaflet see Figure 2 and asked to provide written informed consent that they agree to participate in the study via a consent form
The independent assessor will then collect data at baseline for the outcome measures outlined Please refer to outcomes section for full details
Datastatistical analysis
Descriptive statistics and estimation using 95 CIs will be the main focus of the analysis The number of participants recruited and retained and information on missing or incomplete data from all outcome measures will be explored Baseline demographics and outcome variables will be compared at all assessment times within groups
For categorical measures frequencies and percentages will be presented and for continuous measures the mean and standard deviation SD will be reported For continuous measures which show evidence of some skew a median and interquartile range may also be presented or substituted for the mean and SD Within group change scores and their 95 CI will be examined in relation to the MCID Repeated measures ANOVAs will be used to compare between group differences of continuous variables across the three time points Statistical significance will be determined α-priori at an alpha level of 005
For analysis of EEG data this will be an exploratory analysis using a multilevel linear mixed model LMM approach to examine differences between the intervention groups over time in the EEG alpha beta and theta band power Repeated measures within participants will be modelled as a random effect Fixed effects in the model will include group assignment and time The moderating effects of pain intensity and interference will also be evaluated The LMM will study both main effects and interaction effects using the R package lme4 to fit the models Models will be compared using Likelihood Ratio Tests LRT to assess the significance of effects Statistical significance will be determined α-priori at an alpha level of 005
When all data is collected data analysis will be conducted by a data processor blinded to group allocation A full statistical analysis plan will be prepared prior to final analysis Statistical analysis will be conducted using SPSS version 29 software and analysis will be conducted as intention to treat ITT and per protocol
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None