Clinical trial NCT04496609: Assessment of the Efficacy and Safety of EESS in Patients With Incomplete Spinal Cord Injuries
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Spinal Cord Injuries
Lead sponsor: Hopital Foch
Sponsor class: OTHER
First posted: 2020-08-03
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Assessment of number of patients able to move over a distance of 5 metres
timeFrame: through study completion
Secondary outcomes:
measure: Percentage of patients capable of moving at the end of treatment
timeFrame: 1 hour
measure: Assessment of vesico-sphincter function
timeFrame: 1 hour
measure: Assessment of the genito-sexual function
timeFrame: 30 minutes
measure: Assessment of the excitability of the spinal neuronal circuits
timeFrame: 1 hour
measure: Assessment of the kinetics of action of the induced effects
timeFrame: 1 hour
measure: Assessment of capability to move over a distance of 5 metres at the end of washout period for treatment combining EESS and rehabilitation program
timeFrame: throughout the study
measure: Assessment of capability to move over a distance of 5 metres at the end of washout period for rehabilitation program
timeFrame: 30 minutes
measure: Assessment of capability to move over a distance of 5 metres after 6 months of treatment
timeFrame: Month 6
measure: Assessment of vesico-sphincter function at the end of washout period for treatment combining EESS and rehabilitation program
timeFrame: 1 hour
measure: Assessment of vesico-sphincter function at the end of washout period for rehabilitation program
timeFrame: 1 hour
measure: Assessment of vesico-sphincter function after 6 months of treatment
timeFrame: Month 6
measure: Assessment of the genito-sexual function at the end of washout period for treatment combining EESS and rehabilitation program
timeFrame: 30 minutes
measure: Assessment of the genito-sexual function at the end of washout period for rehabilitation program
timeFrame: 30 minutes
measure: Assessment of the genito-sexual function after 6 months of treatment
timeFrame: Month 6
measure: Assessment of the excitability of the spinal neuronal circuits at the end of washout period for treatment combining EESS and rehabilitation program
timeFrame: 1 hour
measure: Assessment of the excitability of the spinal neuronal circuits at the end of washout period for rehabilitation program
timeFrame: 1 hour
measure: Assessment of the excitability of the spinal neuronal circuits after 6 months of treatment
timeFrame: 1 hour
measure: Assessment of quality of life
timeFrame: 30 minutes
measure: Number of patient with AE/SAE related to tolerance
timeFrame: through study completion
measure: Number of patient with AE/SAE related to safety
timeFrame: through study completion
Other outcomes:
Locations:
city: Garches
country: France
facility: Hôpital Raymond Poincaré
city: Suresnes
country: France
facility: Hôpital Foch
Study officials:
affiliation: Hôpital Foch
name: Béchir Jarraya, MD
role: PRINCIPAL_INVESTIGATOR
References: