Effect of Transorbital Electrical STIMulation of Optic Nerve on Remyelination After an Acute Optic Neuritis

NCT ID: NCT04042363

Last Updated: 2019-08-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-10
• Study Completion Date: 2022-07-31

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.

Conditions

Multiple Sclerosis; Optic Neuritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Active Transorbital electrical stimulation

Transorbital electrical stimulation of the optic nerve - 10 sessions during 2 consecutive weeks

Group Type: EXPERIMENTAL

Transorbital electrical stimulation (Eyetronic Next Wave 1.1)

Intervention Type: DEVICE

Calibration phase: The patient will use a response button to indicate the threshold from which he feels a luminous sensation (phosphene). In a second step, he will use the same answer button to indicate the stimulation frequency from which the phosphenes become continuous.

Stimulation phase: From these 2 parameters (amplitude and frequency), the stimulation session will begin for a duration of approximately 40 to 50 minutes, the settings being dependent of the individual thresholds.

Sham Transorbital stimulation

Sham stimulation - 10 sessions during 2 consecutive weeks

Group Type: SHAM_COMPARATOR

Transorbital electrical stimulation (Eyetronic Next Wave 1.1) - Sham stimulation

Intervention Type: DEVICE

The calibration phase is identical to the active stimulation. During the stimulation phase, the operator will manually interrupt the stimulation 60 seconds after the start of the session.

Interventions

Transorbital electrical stimulation (Eyetronic Next Wave 1.1)

Calibration phase: The patient will use a response button to indicate the threshold from which he feels a luminous sensation (phosphene). In a second step, he will use the same answer button to indicate the stimulation frequency from which the phosphenes become continuous.

Stimulation phase: From these 2 parameters (amplitude and frequency), the stimulation session will begin for a duration of approximately 40 to 50 minutes, the settings being dependent of the individual thresholds.

Intervention Type: DEVICE

Transorbital electrical stimulation (Eyetronic Next Wave 1.1) - Sham stimulation

The calibration phase is identical to the active stimulation. During the stimulation phase, the operator will manually interrupt the stimulation 60 seconds after the start of the session.

Intervention Type: DEVICE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Fondation ARSEP

UNKNOWN

Sponsor Role: collaborator

APHP

OTHER

Sponsor Role: collaborator

Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Céline Louapre

Role: PRINCIPAL_INVESTIGATOR

Institut du Cerveau et de la Moelle Epiniere, Pitie Salpetriere Hospital, Paris

Saddek Mohand-Said

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris

Locations

Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts

Paris, , France

Site Status: RECRUITING

Institut du Cerveau et de la Moelle epiniere - Hopital Pitie Salpetriere

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Hayet Serhane

Role: CONTACT

hserhane@15-20.fr

+33 140021144

Celine Louapre

Role: CONTACT

celine.louapre@aphp.fr

+ 33 1 42 16 57 66

Facility Contacts

Michel PAQUES, PU-PH

Role: primary

mpaques@15-20.fr

01 40 02 14 15

Celine Louapre

Role: primary

Other Identifiers

2018-A03138-47

Identifier Type: OTHER

Identifier Source: secondary_id

P18-03

Identifier Type: -

Identifier Source: org_study_id