Multiple SclerosisONSTIMNCT04042363
Effect of Transorbital Electrical STIMulation of Optic Nerve on Remyelination After an Acute Optic Neuritis
A study testing Transorbital electrical stimulation (Eyetronic Next Wave 1.1) in people with Multiple Sclerosis and Optic Neuritis, run by Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts at 2 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis, Optic Neuritis
- What is being tested?
- Transorbital electrical stimulation (Eyetronic Next Wave 1.1)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 2 sitesFrance
- Study dates
- 10 Jul 2019to Jul 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- For patients:
- Differential diagnosis of Optic neuritis:
- 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.
Show all 15Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
France2 sites, 2 recruiting
- Recruiting
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
Paris, 75012
Michel PAQUES, PU-PH, 01 40 02 14 15, mpaques@15-20.fr
- Recruiting
Institut du Cerveau et de la Moelle epiniere - Hopital Pitie Salpetriere
Paris
Celine Louapre
About this study
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.
Read the 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
- Being tested
- Transorbital electrical stimulation (Eyetronic Next Wave 1.1), Transorbital electrical stimulation (Eyetronic Next Wave 1.1) - Sham stimulation
- Keywords
- multiple sclerosis, optic neuritis, transorbital stimulation, remyelination, nervous system disease, peripheral nervous system disease, optic nerve disease, adaptive optic
- Medical subject headings
- Multiple Sclerosis, Optic Neuritis, Nervous System Diseases, Peripheral Nervous System Diseases, Optic Nerve Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transorbital electrical stimulation (Eyetronic Next Wave 1.1)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.
Transorbital electrical stimulation (Eyetronic Next Wave 1.1) - Sham stimulationDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Active Transorbital electrical stimulation | Experimental | Transorbital electrical stimulation of the optic nerve - 10 sessions during 2 consecutive weeks Receives: Device: Transorbital electrical stimulation (Eyetronic Next Wave 1.1) |
| Sham Transorbital stimulation | Sham comparator | Sham stimulation - 10 sessions during 2 consecutive weeks Receives: Device: Transorbital electrical stimulation (Eyetronic Next Wave 1.1) - Sham stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 weeks
Secondary outcomes (7)
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.
Measured: 24 weeks
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.
Measured: 12 and 48 weeks
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.
Measured: 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
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.
Measured: 12, 24 and 48 weeks
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.
Measured: 12, 24 and 48 weeks
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.
Measured: 12, 24 and 48 weeks
Occurrence of adverse events related or not to the stimulation
Reporting of adverse events related or not to the stimulation
Measured: through study completion, an average of 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2019
- Study start10 Jul 2019
- Primary completionJul 2021 (estimated)
- Study completionJul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
- Sponsor type
- University, hospital or other
- Collaborators
- Fondation ARSEP, APHP
- Responsible party
- Sponsor
- Investigators
- Céline Louapre, Principal investigator, Institut du Cerveau et de la Moelle Epiniere, Pitie Salpetriere Hospital, ParisSaddek Mohand-Said, Principal investigator, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04042363
- Sponsor's protocol ID
- P18-03
- Other IDs
- 2018-A03138-47
- Acronym
- ONSTIM
- Status last verified
- Jul 2019
- First submitted
- 16 Jul 2019
- Last updated
- 28 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Transorbital Electrical STIMulation of Optic Nerve on Remyelination After an Acute Optic Neuritis
- ClinicalTrials.gov ID
- NCT04042363
- Acronym / sponsor ID
- ONSTIM / P18-03
- 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
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Centre Hospitalier National d'Ophtalmologie des Quinze-VingtsUniversity, hospital or other
- Collaborators
- Fondation ARSEP, APHP
- Study start
- 10 Jul 2019 (actual)
- Primary completion
- Jul 2021 (estimated)
- Study completion
- Jul 2022 (estimated)
- First posted
- 1 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Transorbital electrical stimulation | Experimental | Device: Transorbital electrical stimulation (Eyetronic Next Wave 1.1)Transorbital electrical stimulation of the optic nerve - 10 sessions during 2 consecutive weeks |
| Sham Transorbital stimulation | Sham comparator | Device: Transorbital electrical stimulation (Eyetronic Next Wave 1.1) - Sham stimulationSham stimulation - 10 sessions during 2 consecutive weeks |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (15 listed)
- 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
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Device | Active Transorbital electrical stimulation |
| Transorbital electrical stimulation (Eyetronic Next Wave 1.1) - Sham stimulationThe 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. | Device | Sham Transorbital stimulation |
Primary outcome
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.
7 secondary outcomes
Change of P100 amplitude (VEP) after treatment
Time frame: 24 weeks
Change of P100 latency and amplitude (VEP) after treatment
Time frame: 12 and 48 weeks
Evolution of macular volume after treatment
Time frame: 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
Time frame: 12, 24 and 48 weeks
Change of average thickness of macular ganglion cell layer after treatment
Time frame: 12, 24 and 48 weeks
Change of mean deflection of visual field 24-2 after treatment
Time frame: 12, 24 and 48 weeks
Occurrence of adverse events related or not to the stimulation
Time frame: through study completion, an average of 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Céline Louapre principal investigator
Institut du Cerveau et de la Moelle Epiniere, Pitie Salpetriere Hospital, Paris
Saddek Mohand-Said principal investigator
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Paris
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transorbital electrical stimulation (Eyetronic Next Wave 1.1) in people with Multiple Sclerosis and Optic Neuritis, run by Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hayet Serhane (+33 140021144, hserhane@15-20.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
P100 latency (VEP) after treatment (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2019.