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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injuries
• Intervention / Treatment: Device: Stimulation and automated rehabilitation / automated rehabilitation; Device: Automated rehabilitation / Stimulation and automated rehabilitation

• Study Type: Interventional
• Enrollment (Anticipated): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Garches, France, 92380
    • Recruiting
    • Hopital Raymond Poincare
    • Contact: Nicolas Roche, MD; Phone Number: +33 1 47 10 79 00; Email: nicolas.roche@aphp.fr
    • Principal Investigator: Nicolas ROCHE, MD
  • Suresnes, France, 92150
    • Recruiting
    • Hopital Foch
    • Contact: Béchir Jarraya, MD; Phone Number: +33 1 46 25 29 66; Email: b.jarraya@hopital-foch.com
    • Principal Investigator: Béchir Jarraya, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stimulation-automated rehabilitation/automated rehabilitation; 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; Stimulation and automated rehabilitation for 40 working days, then washout during 30 days, then automated rehabilitation for 40 working days
Experimental: Automated rehabilitation/Stimulation-automated rehabilitation; 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; Automated rehabilitation for 40 working days, then washout during 30 days, then automated rehabilitation for 40 working days

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hopital Foch
• Investigators: Principal Investigator: Béchir Jarraya, MD, Hopital Foch

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Anticipated): July 15, 2023
• Study Completion (Anticipated): July 15, 2023

Study Registration Dates

• First Submitted: July 20, 2020
• First Submitted That Met QC Criteria: July 29, 2020
• First Posted (Actual): August 3, 2020

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 2, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Wounds and Injuries; Spinal Cord Injuries
• Other Study ID Numbers: 2016/50

Drug and device information, study documents

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