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

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ClinicalTrials.gov Identifier: NCT04042363
Recruitment Status : Recruiting
First Posted : August 1, 2019
Last Update Posted : August 26, 2019
Sponsor:
Collaborators:
Fondation ARSEP
APHP
Information provided by (Responsible Party):
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts

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.


Condition or disease Intervention/treatment Phase
Multiple Sclerosis Optic Neuritis Device: Transorbital electrical stimulation (Eyetronic Next Wave 1.1) Device: Transorbital electrical stimulation (Eyetronic Next Wave 1.1) - Sham stimulation Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes 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).

Primary Purpose: Treatment
Official Title: Effect of Transorbital Electrical STIMulation of Optic Nerve on Remyelination After an Acute Optic Neuritis
Actual Study Start Date : July 10, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Active Transorbital electrical stimulation
Transorbital electrical stimulation of the optic nerve - 10 sessions during 2 consecutive weeks
Device: 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.


Sham Comparator: Sham Transorbital stimulation
Sham stimulation - 10 sessions during 2 consecutive weeks
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.




Primary Outcome Measures :
  1. P100 latency (VEP) after treatment [ Time Frame: 24 weeks ]
    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 :
  1. Change of P100 amplitude (VEP) after treatment [ Time Frame: 24 weeks ]
    Modification of the amplitude of P100 wave measured by Visual Evoked Potential (VEP) after 24 weeks of treatment with electrical or sham stimulation.

  2. Change of P100 latency and amplitude (VEP) after treatment [ Time Frame: 12 and 48 weeks ]
    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.

  3. Evolution of macular volume after treatment [ Time Frame: 12, 24 and 48 weeks ]
    Evolution since inclusion of macular volume (with Optical Coherence Tomography) at weeks 12, 24 and 48 after transorbital electrical treatment or sham stimulation.

  4. Change of mean and temporal Retinal Nerve Fiber Layer (RNFL) thickness and average thickness of macular ganglion cell layer after treatment [ Time Frame: 12, 24 and 48 weeks ]
    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.

  5. Change of average thickness of macular ganglion cell layer after treatment [ Time Frame: 12, 24 and 48 weeks ]
    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.

  6. Change of mean deflection of visual field 24-2 after treatment [ Time Frame: 12, 24 and 48 weeks ]
    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.

  7. Occurrence of adverse events related or not to the stimulation [ Time Frame: through study completion, an average of 3 years ]
    Reporting of adverse events related or not to the stimulation



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04042363


Contacts
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Contact: Hayet Serhane +33 140021144 hserhane@15-20.fr
Contact: Celine Louapre + 33 1 42 16 57 66 celine.louapre@aphp.fr

Locations
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France
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts Recruiting
Paris, France, 75012
Contact: Michel PAQUES, PU-PH    01 40 02 14 15    mpaques@15-20.fr   
Institut du Cerveau et de la Moelle epiniere - Hopital Pitie Salpetriere Recruiting
Paris, France
Contact: Celine Louapre         
Sponsors and Collaborators
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
Fondation ARSEP
APHP
Investigators
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Principal Investigator: Céline Louapre Institut du Cerveau et de la Moelle Epiniere, Pitie Salpetriere Hospital, Paris
Principal Investigator: Saddek Mohand-Said Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris

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Responsible Party: Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
ClinicalTrials.gov Identifier: NCT04042363     History of Changes
Other Study ID Numbers: P18-03
2018-A03138-47 ( Other Identifier: ID RCB )
First Posted: August 1, 2019    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts:
multiple sclerosis
optic neuritis
transorbital stimulation
remyelination
nervous system disease
peripheral nervous system disease
optic nerve disease
adaptive optic
Additional relevant MeSH terms:
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Multiple Sclerosis
Neuritis
Optic Neuritis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Optic Nerve Diseases
Cranial Nerve Diseases
Eye Diseases