Acute Autoimmune Inflammatory Optic Neuritis
Conditions
Keywords
optic neuritis, multiple sclerosis, repetitive transorbital alternating current stimulation, optical coherence tomography, low-contrast visual acuity
Brief summary
Optic neuritis (ON) is an acute inflammatory, demyelinating attack of the optic nerve that triggers neurodegeneration in the entire visual pathway; translating into visual dysfunction. Currently, no neuroprotective therapy with satisfying evidence can be offered to patients. Repetitive transorbital alternating current stimulation (rtACS) is a methodology applied to electrically stimulate the retina and the optic nerve and is considered having neuroprotective- and restorative potential. The goal of this pilot study is to assess safety, tolerability and preliminary efficacy of rtACS as a treatment to improve visual functional as well as structural retinal outcomes in patients with a first-ever episode of autoimmune acute ON.
Interventions
DEVICEactive-rtACS treatment
For the active-rtACS treatment arm, a CE-certificated proprietary class IIa medical device will be used to apply transorbital symmetrical rectangular current pulses in bursts (NextWave® 1.1 system; EBS Technologies GmbH, Germany). The stimulation protocol will be patient-individualized, with a stimulation current strength of 125% of the phosphene threshold recorded during 5Hz stimulation and stimulation frequencies between the individual's EEG alpha frequency and their flicker fusion frequency.
DEVICEsham-rtACS treatment
For the sham-rtACS treatment arm, exactly the same medical device, setup, time schedule, etc. will be used as for the patients of the active-rtACS arm. However, sham-treated patients will receive no actual current stimulation during the therapy sessions.
Sponsors
University Hospital, Zürich
Swiss MS Society
Data Management, Clinical Trials Center, Zurich, Switzerland
University of Zurich
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
Participants fulfilling all of the following inclusion criteria are eligible for the study: * Informed Consent as documented by signature * Participants are capable of giving informed consent * Participant who have a good knowledge of German (patient information and consent must be understood) * Patients, presenting with typical signs and symptoms suggestive of a first-ever episode of unilateral acute autoimmune, inflammatory, demyelinating ON, including idiopathic ON and ON suggestive of multiple sclerosis (MS) (typical clinically isolated syndrome, or with an established diagnosis of relapsing-remitting MS according to latest panel criteria and no better explanation) * Patients with high-contrast visual acuity of ≤ 0.63 (decimal system) corresponding to a LogMAR value of ≥ 0.2 on the affected eye (assessed using a Snellen chart during clinical routine) * Patients presenting in clinics within 14 days of symptom onset * In principle 18-50 year old female and male patients may be recruited. However, since the randomization of patients will be controlled for gender and participants will be enrolled one at a time on a continuous basis, the gender might become relevant late in the study (e.g. if the female block has already been fully recruited and only males might still be enrolled). * Patients are receiving standard-of-care treatment for ON (cortisone therapy)
Exclusion criteria
The presence of any one of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary functional outcome measure will be low-contrast visual acuity [LogMAR] at 16 weeks (3 month follow-up) in ON eyes. | 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day) |
| The primary structural outcome measure will be the mean change in macular ganglion cell and inner plexiform layer thickness [µm] of the affected ON eye at 16 weeks in comparison to baseline of the unaffected contralateral NON eye (pre-treatment). | Baseline (pre-treatment, i.e. 1 week after recruitment), 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day) |
| The primary safety outcome measure will be the total number of adverse events during the entire study period | up to 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| High-contrast visual acuity [LogMAR] at 4 weeks (post-treatment) in ON eyes. | post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day) | — |
| Colour vision [tritan] at 16 weeks (3 month follow-up) in ON eyes. | 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day) | — |
| Colour vision [tritan] at 4 weeks (post-treatment) in ON eyes. | post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day) | — |
| Visual field testing [dB] at 16 weeks (3 month follow-up) in ON eyes. | 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day) | — |
| Visual field testing [dB] at 4 weeks (post-treatment) in ON eyes. | post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day) | — |
| Recovery of pattern-reversal visual evoked potential conduction velocity of the affected optic nerve [ms] compared to the intra-individual baseline of the unaffected optic nerve at 16 weeks (3 month follow-up). | Baseline (pre-treatment, i.e. 1 week after recruitment), 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day) | — |
| Low-contrast visual acuity [LogMAR] at 4 (post-treatment) weeks in ON eyes. | post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day) | — |
| Patient-reported vision-related quality of life assessed by the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) at 4 weeks (post-treatment). | post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day) | The questionnaire contains the following 12 sub-scales: general health, general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, colour vision and peripheral vision. The mean VFQ-25 composite score (calculated as an unweighted average of responses to all items except for the general health sub-scale) and selected sub-scale scores will be analysed. Each sub-scale, and also the composite score, will be quantified with values between 0-100, with zero being the worst and 100 being the best. |
| The mean change in peripapillary retinal nerve fibre layer (pRNFL) thickness [µm] of the affected ON eye at 16 weeks (3 month follow-up) in comparison to baseline of the contralateral NON eye. | Baseline (pre-treatment, i.e. 1 week after recruitment), 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day) | — |
| The mean change in peripapillary retinal nerve fibre layer (pRNFL) thickness [µm] of the affected ON eye at 4 weeks (post-treatment) in comparison to baseline of the contralateral NON eye. | Baseline (pre-treatment, i.e. 1 week after recruitment), post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day) | — |
| The mean change in macular inner nuclear layer (INL) thickness [µm] of the affected ON eye at 16 weeks (3 month follow-up) in comparison to baseline of the contralateral NON eye. | Baseline (pre-treatment, i.e. 1 week after recruitment), 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day) | — |
| The mean change in macular inner nuclear layer (INL) thickness [µm] of the affected ON eye at 4 (post-treatment) weeks in comparison to baseline of the contralateral NON eye. | Baseline (pre-treatment, i.e. 1 week after recruitment), post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day) | — |
| Patient-reported vision-related quality of life assessed by the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) at 16 weeks (3 month follow-up). | 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day) | The questionnaire contains the following 12 sub-scales: general health, general vision, ocular pain, near activities, distance activities, vision-specific social functioning, vision-specific mental health, vision-specific role difficulties, vision-specific dependency, driving, colour vision and peripheral vision. The mean VFQ-25 composite score (calculated as an unweighted average of responses to all items except for the general health sub-scale) and selected sub-scale scores will be analysed. Each sub-scale, and also the composite score, will be quantified with values between 0-100, with zero being the worst and 100 being the best. |
| The mean change in macular ganglion cell and inner plexiform layer thickness [µm] of the affected ON eye at 4 weeks in comparison to baseline of the unaffected contralateral NON eye (pre-treatment). | Baseline (pre-treatment, i.e. 1 week after recruitment), post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day) | — |
| High-contrast visual acuity [LogMAR] at 16 weeks (3 month follow-up) in ON eyes. | 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day) | — |
Countries
Switzerland
Outcome results
None listed