NCT04042363

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
45

participants targeted

Target at P50-P75 for not_applicable multiple-sclerosis

Timeline
Completed

Started Jul 2019

Typical duration for not_applicable multiple-sclerosis

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 10, 2019

Completed
6 days until next milestone

First Submitted

Initial submission to the registry

July 16, 2019

Completed
16 days until next milestone

First Posted

Study publicly available on registry

August 1, 2019

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2021

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2022

Completed
Last Updated

August 28, 2019

Status Verified

July 1, 2019

Enrollment Period

2 years

First QC Date

July 16, 2019

Last Update Submit

August 23, 2019

Conditions

Keywords

multiple sclerosisoptic neuritistransorbital stimulationremyelinationnervous system diseaseperipheral nervous system diseaseoptic nerve diseaseadaptive optic

Outcome Measures

Primary Outcomes (1)

  • 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.

    24 weeks

Secondary Outcomes (7)

  • Change of P100 amplitude (VEP) after treatment

    24 weeks

  • Change of P100 latency and amplitude (VEP) after treatment

    12 and 48 weeks

  • Evolution of macular volume after treatment

    12, 24 and 48 weeks

  • Change of mean and temporal Retinal Nerve Fiber Layer (RNFL) thickness and average thickness of macular ganglion cell layer after treatment

    12, 24 and 48 weeks

  • Change of average thickness of macular ganglion cell layer after treatment

    12, 24 and 48 weeks

  • +2 more secondary outcomes

Study Arms (2)

Active Transorbital electrical stimulation

EXPERIMENTAL

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

Device: Transorbital electrical stimulation (Eyetronic Next Wave 1.1)

Sham Transorbital stimulation

SHAM COMPARATOR

Sham stimulation - 10 sessions during 2 consecutive weeks

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

Interventions

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.

Active Transorbital electrical 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.

Sham Transorbital stimulation

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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)
  • 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

You may not qualify if:

  • For patients:
  • Differential diagnosis of Optic neuritis:
  • 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
  • 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
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts

Paris, 75012, France

RECRUITING

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

Paris, France

RECRUITING

MeSH Terms

Conditions

Multiple SclerosisOptic NeuritisNervous System DiseasesPeripheral Nervous System DiseasesOptic Nerve Diseases

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemDemyelinating DiseasesAutoimmune DiseasesImmune System DiseasesCranial Nerve DiseasesEye DiseasesNeuromuscular Diseases

Study Officials

  • 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

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Masking Details
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).
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 16, 2019

First Posted

August 1, 2019

Study Start

July 10, 2019

Primary Completion

July 1, 2021

Study Completion

July 1, 2022

Last Updated

August 28, 2019

Record last verified: 2019-07

Locations