Assessment of the Efficacy and Safety of EESS in Patients With Incomplete Spinal Cord Injuries

Study Overview
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Brief Summary
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Neurological disability caused by traumatic lesions of the spinal cord is a significant challenge for medicine and society. These lesions, leading to sublesional central nervous system dysfunction, include sensorimotor, vesico-sphincter and genito-sexual disorders. To date, there is no treatment that enables spinal cord function to be restored. Preclinical studies have been able to demonstrate the recovery of locomotor activity with a combination of locomotor training, pharmacological intervention and epidural electrical stimulation of the lumbosacral spinal cord (EESS) in adult rats with spinal cord transection. An American team have recently been able to show that EESS, combined with locomotor training, caused neurological improvement in four paraplegic patients, with electromyographic muscular activation patterns similar to those observed during walking. In fact, these authors also showed an improvement, under stimulation, of the VS and GS functions, but with no detailed documentation. Starting with a conceptual and preclinical rationale, and with proof of clinical concept demonstrated in several reported cases, we propose a clinical trial with an original cross-over design to validate the hypothesis that EESS combined with training in patients with incomplete spinal cord injuries would, with a good tolerance profile, allow motor, vesico-sphincter (VS) and genito-sexual (GS) disorders to be restored in patients with incomplete spinal cord injuries.

Official Title
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Assessment of the Efficacy and Safety of Epidural Electrical Stimulation of the Lumbosacral Spinal Cord in the Symptomatic Treatment of Motor, Vesico-sphincter and Genito-sexual Disorders in Patients With Incomplete Spinal Cord Injuries

Conditions
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Spinal Cord Injuries

Intervention / Treatment
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* Device: Stimulation and automated rehabilitation / automated rehabilitation
* Device: Automated rehabilitation / Stimulation and automated rehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 18 and 65 years inclusive Male or female Incomplete ASIA B or C spinal cord lesion with level of lesion located above T10 (sensation preserved below level of lesion) Absence of significant motor deficit of the upper limbs or recovered motor deficit (muscular score ≥ 4/5) Patient with spinal cord injury at least 2 years old and considered stable not walking Spinal cord lesion determined by spinal cord MRI (intramedullary hypersignal) Patient who can benefit from an iterative rehabilitation programme Patient with stable health condition with no cardiopulmonary disease Patient with orthopaedic condition compatible with verticality and walking Persistence of adductor reflexes up to L2 Patient with no current neuromodulation implant: spinal cord neurostimulator, brain, peripheral nerve or intrathecal treatment Patient with no coagulopathy, cardiac risk factors or other medical risk factors significant for surgery Local anatomical conditions compatible with implantation of the epidural electrode (determined by MRI of the spinal cord) Person who benefits from or is entitled to a social security scheme Having provided signed informed consent Exclusion Criteria: Significant cerebral lesion on a previous cerebral MRI Psychiatric or cognitive disorder history (known or detected during the consultation with the psychologist) Protected adult patients Pregnant (determined by a negative pregnancy test) or breastfeeding women Respiratory failure (vital capacity < 50%) (surgery in prone position) Repeated urinary infections (≥3 per year) Planned absence that may hinder participation in the study (travelling abroad, relocation, imminent moving) Patients with spasms (PENN scale > 2) Cauda equina syndrome Patients presenting with a contraindication to an MRI being carried out: i) pacemaker, ii) non-MRI-compatible heart valve, iii) clips, stents, coils, etc. that are not MRI-compatible, iv) cochlear implant, v) metal foreign body, etc.) Patients presenting with a contraindication to MEPs being carried out (notably wearing of ferromagnetic material, heart stimulator) Patients on oral anticoagulants Patients with botulinic toxin injection Patients with bedsore Undernourished patients (BMI < 19)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stimulation-automated rehabilitation/automated rehabilitation<br>Stimulation and automated rehabilitation (2 sessions of 45 minutes per day) for 40 working days Washout 30 days Automated rehabilitation (2 sessions of 45 minutes per day) for 40 working days | Device: Stimulation and automated rehabilitation / automated rehabilitation<br>* Stimulation and automated rehabilitation for 40 working days, then washout during 30 days, then automated rehabilitation for 40 working days<br>|
| Experimental: Automated rehabilitation/Stimulation-automated rehabilitation<br>Automated rehabilitation (2 sessions of 45 minutes per day) for 40 working days Washout 30 days Stimulation and automated rehabilitation (2 sessions of 45 minutes per day) for 40 working days | Device: Automated rehabilitation / Stimulation and automated rehabilitation<br>* Automated rehabilitation for 40 working days, then washout during 30 days, then automated rehabilitation for 40 working days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of number of patients able to move over a distance of 5 metres | Determined by a capability to move over a distance of 5 metres with or without technical aid, with the option of stopping on the way | through study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients capable of moving at the end of treatment | Based on the rehabilitation programme over a distance of 5 metres with or without technical aid, with the option of stopping on the way, Surface EMG, Bipodal balance measurement | 1 hour | 
| Assessment of vesico-sphincter function | Measurement using cystomanometry, flow measurement and assessment of post-micturition residue by means of a bladder scan | 1 hour | 
| Assessment of the genito-sexual function | Measurement with MSHQ (Male Sexual Health Questionnaire) scale in men and FSFI (Female Sexual Function Index) in women MSHQ scale: minimum value (worse outcome): 7 - maximum value (better outcome): 80 FSFI scale: minimum value:2 (worse outcome) - maximum value: 36 (better outcome) | 30 minutes | 
| Assessment of the excitability of the spinal neuronal circuits | Measurement of the reciprocal inhibition directed from the tibialis anterior to the soleus and the presynaptic inhibition applied to the fibres of the soleus by modifying the range of the soleus H-reflex obtained by percutaneous peripheral nerve electrical stimulation | 1 hour | 
| Assessment of the kinetics of action of the induced effects | Assessment according to the epidural electrical stimulation paradigms | 1 hour | 
| Assessment of capability to move over a distance of 5 metres at the end of washout period for treatment combining EESS and rehabilitation program | Measurement of covered distance at the end of washout period for treatment combining EESS and rehabilitation program | throughout the study | 
| Assessment of capability to move over a distance of 5 metres at the end of washout period for rehabilitation program | Measurement of covered distance at the end of washout period for rehabilitation program | 30 minutes | 
| Assessment of capability to move over a distance of 5 metres after 6 months of treatment | Measurement of covered distance after 6 months of treatment | Month 6 | 
| Assessment of vesico-sphincter function at the end of washout period for treatment combining EESS and rehabilitation program | Measurement using cystomanometry, flow measurement and assessment of post-micturition residue by means of a bladder scan | 1 hour | 
| Assessment of vesico-sphincter function at the end of washout period for rehabilitation program | Measurement using cystomanometry, flow measurement and assessment of post-micturition residue by means of a bladder scan | 1 hour | 
| Assessment of vesico-sphincter function after 6 months of treatment | Measurement using cystomanometry, flow measurement and assessment of post-micturition residue by means of a bladder scan | Month 6 | 
| Assessment of the genito-sexual function at the end of washout period for treatment combining EESS and rehabilitation program | Measurement with MSHQ (Male Sexual Health Questionnaire) scale in men and FSFI (Female Sexual Function Index) in women MSHQ scale: minimum value (worse outcome): 7 - maximum value (better outcome): 80 FSFI scale: minimum value:2 (worse outcome) - maximum value: 36 (better outcome) | 30 minutes | 
| Assessment of the genito-sexual function at the end of washout period for rehabilitation program | Measurement with MSHQ (Male Sexual Health Questionnaire) scale in men and FSFI (Female Sexual Function Index) in women MSHQ scale: minimum value (worse outcome): 7 - maximum value (better outcome): 80 FSFI scale: minimum value:2 (worse outcome) - maximum value: 36 (better outcome) | 30 minutes | 
| Assessment of the genito-sexual function after 6 months of treatment | Measurement with MSHQ (Male Sexual Health Questionnaire) scale in men and FSFI (Female Sexual Function Index) in women MSHQ scale: minimum value (worse outcome): 7 - maximum value (better outcome): 80 FSFI scale: minimum value:2 (worse outcome) - maximum value: 36 (better outcome) | Month 6 | 
| Assessment of the excitability of the spinal neuronal circuits at the end of washout period for treatment combining EESS and rehabilitation program | Measurement of the reciprocal inhibition directed from the tibialis anterior to the soleus and the presynaptic inhibition applied to the fibres of the soleus by modifying the range of the soleus H-reflex obtained by percutaneous peripheral nerve electrical stimulation | 1 hour | 
| Assessment of the excitability of the spinal neuronal circuits at the end of washout period for rehabilitation program | Measurement of the reciprocal inhibition directed from the tibialis anterior to the soleus and the presynaptic inhibition applied to the fibres of the soleus by modifying the range of the soleus H-reflex obtained by percutaneous peripheral nerve electrical stimulation | 1 hour | 
| Assessment of the excitability of the spinal neuronal circuits after 6 months of treatment | Measurement of the reciprocal inhibition directed from the tibialis anterior to the soleus and the presynaptic inhibition applied to the fibres of the soleus by modifying the range of the soleus H-reflex obtained by percutaneous peripheral nerve electrical stimulation | 1 hour | 
| Assessment of quality of life | Measurement with EQ5D-3L (EuroQol 5 Dimensions - 3 Levels) scale | 30 minutes | 
| Number of patient with AE/SAE related to tolerance | Reporting of AE and SAE | through study completion | 
| Number of patient with AE/SAE related to safety | Reporting of AE and SAE | through study completion |