Clinical trial NCT04042363: Effect of Transorbital Electrical STIMulation of Optic Nerve on Remyelination After an Acute Optic Neuritis
Official title: Effect of Transorbital Electrical STIMulation of Optic Nerve on Remyelination After an Acute Optic Neuritis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Multiple Sclerosis
Optic Neuritis
Keywords: multiple sclerosis
optic neuritis
transorbital stimulation
remyelination
nervous system disease
peripheral nervous system disease
optic nerve disease
adaptive optic
Lead sponsor: Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
Sponsor class: OTHER
Collaborators: name: Fondation ARSEP
name: APHP
First posted: 2019-08-01
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In light of experimental models showing that neuronal electrical activity is crucial for the remyelination process, we hypothesize that maintenance of electrical axonal activity in the early stages of optic neuritis may promote myelin repair, limiting thereby axonal degeneration.

In humans, electrical stimulation of the optic nerve has been tested mainly in ischemic neuropathy and retinitis pigmentosa, which are both associated with severe axonal/retinal pathology and poor visual prognosis. In contrast, the inflammation of the optic nerve in optic neuritis is generally transient, with less severe axonal damage at the acute phase, which would allow for better efficacy of electrical stimulation as a strategy to promote remyelination and neuroprotection.In light of experimental models showing that neuronal electrical activity is crucial for the remyelination process, we hypothesize that maintenance of electrical axonal activity in the early stages of optic neuritis may promote myelin repair, limiting thereby axonal degeneration.

In humans, electrical stimulation of the optic nerve has been tested mainly in ischemic neuropathy and retinitis pigmentosa, which are both associated with severe axonal/retinal pathology and poor visual prognosis. In contrast, the inflammation of the optic nerve in optic neuritis is generally transient, with less severe axonal damage at the acute phase, which would allow for better efficacy of electrical stimulation as a strategy to promote remyelination and neuroprotection.

Detailed description: This is a randomized, controlled, prospective, interventional, blinded trial which aims to evaluate the safety and efficacy of transorbital electrical nerve stimulation on remyelination and neuroprotection after an acute episode of retrobulbar optic neuritis in patients with multiple sclerosis (MS).

Expected Explorations: The study is composed of 14 visits: a screening/inclusion visit with neurological and ophthalmological evaluation, electrophysiology, MRI and Magnetoencephalography (MEG), 10 transorbital electrical stimulation or sham stimulation visits and finally 3 follow-up visits and evaluations (neurological and ophthalmological). Patient's participation will last 49 weeks (inclusion visit and 48 weeks of follow-up). Participation of healthy volunteers will last one day.

MS patients diagnosed with an optic neuritis will be randomized either in the active arm (transorbital electrical stimulation of the optic nerve - 10 sessions during 2 consecutive weeks) or in the placebo arm (sham stimulation - 10 sessions during 2 consecutive weeks) Expected benefits: Electrical stimulation of the optic nerve after an acute episode of retrobulbar optic neuritis may promote remyelination in the optic nerve and a better long-term visual outcome.

Eligibility criteria: Inclusion Criteria:

* For MS patients:
* Age between 18 and 60 years old.
* Relapsing Remitting MS (criteria of McDonald 2017) evolving for less than 10 years or Clinically Isolated Syndrome (CIS)-MS with criteria of spatial dissemination on MRI
* Subject presenting an acute unilateral episode of optic neuritis treated optimally (bolus of corticosteroids and plasma exchanges if considered necessary)
* Last medical treatment for optic neuritis received between 30 and 90 days before inclusion
* Visual acuity \<7/10 of the affected eye at the time of inclusion
* Social security scheme or beneficiary of such a scheme

For Healthy Volunteers:

* Age between 18 and 60 years old.
* No history of neurological or ophthalmological diseases
* Corrected visual acuity ≥ 8/10
* Scheme or beneficiary of such a scheme

Exclusion Criteria:

For patients:

* Differential diagnosis of Optic neuritis:

  i) Atypical acute optic neuritis (papillitis, severe papilledema, initial optic atrophy) ii) Optic neuromyelitis iii) Normal VEP during the inclusion visit iv) No detection of VEP during the inclusion visit
* Impossibility to perform MRI, MEG, or electrical stimulation:

Pacemaker or neurosensory stimulator or implantable defibrillator Clip on an aneurysm or clip on a vascular malformation of the brain Cochlear implants Ocular or cerebral ferromagnetic foreign bodies Metal prostheses or metal clips or splinters Ventriculoperitoneal neurosurgical bypass valves Permanent makeup of the eyelids or lips Black tattoo, important and close to the cranio-facial sphere. Copper Intrauterine Device Person with proven claustrophobia Epilepsy Brain tumor Intraocular pressure without specific treatment Hypertension without treatment Acute retinal hemorrhage Periorbital skin irritation Significant cognitive deficit Known gadolinium allergy

* Person with severe or uncontrolled symptoms of kidney, liver, hematological, gastrointestinal, pulmonary or cardiac disease or any uncontrolled intercurrent disease at the time of inclusion.
* Pregnant or breath-feeding woman.
* Refusal of the participant to be informed in case of fortuitous discoveries having a direct impact on his health and requiring appropriate care
* person under judicial protection or deprived of liberty

For healthy volunteers:

* Contraindication to MRI or MEG
* Person with severe or uncontrolled symptoms of kidney, liver, hematological disease, gastrointestinal, pulmonary or cardiac disease or any uncontrolled intercurrent pathology at the time of inclusion.
* Pregnant or breath-feeding woman.
* Refusal of the participant to be informed in case of fortuitous discoveries having a direct impact on his health and requiring appropriate care
* Person under the protection of justice or deprived of liberty

Primary outcomes:
measure: P100 latency (VEP) after treatment
timeFrame: 24 weeks
Secondary outcomes:
measure: Change of P100 amplitude (VEP) after treatment
timeFrame: 24 weeks
measure: Change of P100 latency and amplitude (VEP) after treatment
timeFrame: 12 and 48 weeks
measure: Evolution of macular volume after treatment
timeFrame: 12, 24 and 48 weeks
measure: Change of mean and temporal Retinal Nerve Fiber Layer (RNFL) thickness and average thickness of macular ganglion cell layer after treatment
timeFrame: 12, 24 and 48 weeks
measure: Change of average thickness of macular ganglion cell layer after treatment
timeFrame: 12, 24 and 48 weeks
measure: Change of mean deflection of visual field 24-2 after treatment
timeFrame: 12, 24 and 48 weeks
measure: Occurrence of adverse events related or not to the stimulation
timeFrame: through study completion, an average of 3 years
Other outcomes:
Locations:
city: Paris
country: France
facility: Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
city: Paris
country: France
facility: Institut du Cerveau et de la Moelle epiniere - Hopital Pitie Salpetriere
Study officials:
affiliation: Institut du Cerveau et de la Moelle Epiniere, Pitie Salpetriere Hospital, Paris
name: Céline Louapre
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris
name: Saddek Mohand-Said
role: PRINCIPAL_INVESTIGATOR
References: