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

Primary Purpose

Multiple Sclerosis, Optic Neuritis

Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Transorbital electrical stimulation (Eyetronic Next Wave 1.1)
Transorbital electrical stimulation (Eyetronic Next Wave 1.1) - Sham stimulation
Sponsored by
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring multiple sclerosis, optic neuritis, transorbital stimulation, remyelination, nervous system disease, peripheral nervous system disease, optic nerve disease, adaptive optic

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Centre Hospitalier National d'Ophtalmologie des Quinze-VingtsRecruiting
  • Institut du Cerveau et de la Moelle epiniere - Hopital Pitie SalpetriereRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Active Transorbital electrical stimulation

Sham Transorbital stimulation

Arm Description

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

Sham stimulation - 10 sessions during 2 consecutive weeks

Outcomes

Primary Outcome Measures

P100 latency (VEP) after treatment
Modification of the latency of P100 wave measured by Visual Evoked Potential (VEP) after 24 weeks of treatment with electrical or sham stimulation.

Secondary Outcome Measures

Change of P100 amplitude (VEP) after treatment
Modification of the amplitude of P100 wave measured by Visual Evoked Potential (VEP) after 24 weeks of treatment with electrical or sham stimulation.
Change of P100 latency and amplitude (VEP) after treatment
Modification of the latency and amplitude of P100 wave measured by Visual Evoked Potential (VEP) after 12 and 48 weeks of treatment with electrical or sham stimulation.
Evolution of macular volume after treatment
Evolution since inclusion of macular volume (with Optical Coherence Tomography) at weeks 12, 24 and 48 after transorbital electrical treatment or sham stimulation.
Change of mean and temporal Retinal Nerve Fiber Layer (RNFL) thickness and average thickness of macular ganglion cell layer after treatment
Evolution since inclusion of mean and temporal Retinal Nerve Fiber Layer (RNFL) thickness and average thickness of macular ganglion cell layer (with Optical Coherence Tomography) at weeks 12, 24 and 48 after transorbital electrical treatment or sham stimulation.
Change of average thickness of macular ganglion cell layer after treatment
Evolution since inclusion of average thickness of macular ganglion cell layer (with Optical Coherence Tomography) at weeks 12, 24 and 48 after transorbital electrical treatment or sham stimulation.
Change of mean deflection of visual field 24-2 after treatment
Change in the mean deflection of visual field 24-2 (24-2 Humphrey visual field analyser) at weeks 12, 24 and 48 compared to inclusion after electrical treatment or sham stimulation.
Occurrence of adverse events related or not to the stimulation
Reporting of adverse events related or not to the stimulation

Full Information

First Posted
July 16, 2019
Last Updated
August 23, 2019
Sponsor
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
Collaborators
Fondation ARSEP, APHP
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1. Study Identification

Unique Protocol Identification Number
NCT04042363
Brief Title
Effect of Transorbital Electrical STIMulation of Optic Nerve on Remyelination After an Acute Optic Neuritis
Acronym
ONSTIM
Official Title
Effect of Transorbital Electrical STIMulation of Optic Nerve on Remyelination After an Acute Optic Neuritis
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Unknown status
Study Start Date
July 10, 2019 (Actual)
Primary Completion Date
July 2021 (Anticipated)
Study Completion Date
July 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
Collaborators
Fondation ARSEP, APHP

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Optic Neuritis
Keywords
multiple sclerosis, optic neuritis, transorbital stimulation, remyelination, nervous system disease, peripheral nervous system disease, optic nerve disease, adaptive optic

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Masking Description
Patients as well as ophthalmologists will be subject to the procedure of masking and will keep the blinding for the duration of the study. As a result, ophthalmologists examiners will not perform electrical stimulation sessions. The persons in charge of the stimulation will be in "open label" and will ensure the inclusion, the follow-up of the patient throughout the study, the stimulation (SHAM or stimulation), the clinical and neurological examination as well as the collection of the treatments and the notification of the Adverse Events/Serious Adverse Events (AE/SAE).
Allocation
Randomized
Enrollment
45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active Transorbital electrical stimulation
Arm Type
Experimental
Arm Description
Transorbital electrical stimulation of the optic nerve - 10 sessions during 2 consecutive weeks
Arm Title
Sham Transorbital stimulation
Arm Type
Sham Comparator
Arm Description
Sham stimulation - 10 sessions during 2 consecutive weeks
Intervention Type
Device
Intervention Name(s)
Transorbital electrical stimulation (Eyetronic Next Wave 1.1)
Intervention Description
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
Intervention Name(s)
Transorbital electrical stimulation (Eyetronic Next Wave 1.1) - Sham stimulation
Intervention Description
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.
Primary Outcome Measure Information:
Title
P100 latency (VEP) after treatment
Description
Modification of the latency of P100 wave measured by Visual Evoked Potential (VEP) after 24 weeks of treatment with electrical or sham stimulation.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Change of P100 amplitude (VEP) after treatment
Description
Modification of the amplitude of P100 wave measured by Visual Evoked Potential (VEP) after 24 weeks of treatment with electrical or sham stimulation.
Time Frame
24 weeks
Title
Change of P100 latency and amplitude (VEP) after treatment
Description
Modification of the latency and amplitude of P100 wave measured by Visual Evoked Potential (VEP) after 12 and 48 weeks of treatment with electrical or sham stimulation.
Time Frame
12 and 48 weeks
Title
Evolution of macular volume after treatment
Description
Evolution since inclusion of macular volume (with Optical Coherence Tomography) at weeks 12, 24 and 48 after transorbital electrical treatment or sham stimulation.
Time Frame
12, 24 and 48 weeks
Title
Change of mean and temporal Retinal Nerve Fiber Layer (RNFL) thickness and average thickness of macular ganglion cell layer after treatment
Description
Evolution since inclusion of mean and temporal Retinal Nerve Fiber Layer (RNFL) thickness and average thickness of macular ganglion cell layer (with Optical Coherence Tomography) at weeks 12, 24 and 48 after transorbital electrical treatment or sham stimulation.
Time Frame
12, 24 and 48 weeks
Title
Change of average thickness of macular ganglion cell layer after treatment
Description
Evolution since inclusion of average thickness of macular ganglion cell layer (with Optical Coherence Tomography) at weeks 12, 24 and 48 after transorbital electrical treatment or sham stimulation.
Time Frame
12, 24 and 48 weeks
Title
Change of mean deflection of visual field 24-2 after treatment
Description
Change in the mean deflection of visual field 24-2 (24-2 Humphrey visual field analyser) at weeks 12, 24 and 48 compared to inclusion after electrical treatment or sham stimulation.
Time Frame
12, 24 and 48 weeks
Title
Occurrence of adverse events related or not to the stimulation
Description
Reporting of adverse events related or not to the stimulation
Time Frame
through study completion, an average of 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hayet Serhane
Phone
+33 140021144
Email
hserhane@15-20.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Celine Louapre
Phone
+ 33 1 42 16 57 66
Email
celine.louapre@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Céline Louapre
Organizational Affiliation
Institut du Cerveau et de la Moelle Epiniere, Pitie Salpetriere Hospital, Paris
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Saddek Mohand-Said
Organizational Affiliation
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
City
Paris
ZIP/Postal Code
75012
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michel PAQUES, PU-PH
Phone
01 40 02 14 15
Email
mpaques@15-20.fr
Facility Name
Institut du Cerveau et de la Moelle epiniere - Hopital Pitie Salpetriere
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Celine Louapre

12. IPD Sharing Statement

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

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