- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03862313
Repetitive Transorbital Alternating Current Stimulation in Acute Autoimmune Optic Neuritis (ACSON)
March 25, 2021 updated by: University of Zurich
Assessing Repetitive Transorbital Alternating Current Stimulation in Acute Autoimmune Inflammatory Optic Neuritis Using the NextWave® 1.1 System: A Prospective, Randomized, Patient-blinded, Sham-controlled Pilot Study
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
2
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Zurich, Switzerland, 8091
- Department of Neurology and Department of Ophthalmology, University Hospital Zurich
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 50 years (ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 exclusion criteria will lead to exclusion of the participant:
- Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial
- Women who are pregnant or have the intention to become pregnant during the course of the study (For women who can get pregnant, pregnancy will be omitted using a pregnancy test when checking for inclusion and exclusion criteria. Patients will be informed that they must use contraception during the study)
- Patients with a previous clinical history of ON in the respective eye
- Patients with obvious retinal pathology other than that associated with ON
- Patients who are unable to perform the study assessments (e.g. OCT examination) because of a severe nystagmus (repetitive, uncontrolled eye movements causing unsteady fixation)
- Patients with a recent eye surgery
- Patients with known anti-aquaporin-4- or myelin oligodendrocyte glycoprotein- antibody seropositivity
- Patients with contraindications to the class of device under study (for rtACS): implanted electronic devices, metallic artefacts in the head (excluding dentition), epilepsy, brain cancer, pregnancy, breastfeeding, increased intraocular pressure without appropriate treatment, arterial hypertension without appropriate treatment, skin irritations at intended positions of electrodes, cognitive deficits (unable to provide written informed consent or follow the instructions)
- Known or suspected non-compliance, drug or alcohol abuse
- Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
- Participation in another study with investigational drug/device within the 30 days preceding and during the present study
- Previous enrolment into the current study
- Enrolment of the investigator, his/her family members, employees and other dependent persons
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: SINGLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: active-rtACS arm
Active rtACS on 10 consecutive working days, in addition to standard-of-care corticosteroid treatment.
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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.
Other Names:
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SHAM_COMPARATOR: sham-rtACS arm
Sham rtACS on 10 consecutive working days, in addition to standard-of-care corticosteroid treatment.
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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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome 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.
Time Frame: 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day)
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3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day)
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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).
Time Frame: 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)
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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)
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The primary safety outcome measure will be the total number of adverse events during the entire study period
Time Frame: up to 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day)
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up to 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Low-contrast visual acuity [LogMAR] at 4 (post-treatment) weeks in ON eyes.
Time Frame: post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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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).
Time Frame: Baseline (pre-treatment, i.e. 1 week after recruitment), post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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Baseline (pre-treatment, i.e. 1 week after recruitment), post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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High-contrast visual acuity [LogMAR] at 16 weeks (3 month follow-up) in ON eyes.
Time Frame: 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day)
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3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day)
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High-contrast visual acuity [LogMAR] at 4 weeks (post-treatment) in ON eyes.
Time Frame: post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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Colour vision [tritan] at 16 weeks (3 month follow-up) in ON eyes.
Time Frame: 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day)
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3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day)
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Colour vision [tritan] at 4 weeks (post-treatment) in ON eyes.
Time Frame: post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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Visual field testing [dB] at 16 weeks (3 month follow-up) in ON eyes.
Time Frame: 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day)
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3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day)
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Visual field testing [dB] at 4 weeks (post-treatment) in ON eyes.
Time Frame: post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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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).
Time Frame: 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)
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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)
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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).
Time Frame: 3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day)
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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.
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3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day)
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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).
Time Frame: post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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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.
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post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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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.
Time Frame: 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)
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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)
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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.
Time Frame: Baseline (pre-treatment, i.e. 1 week after recruitment), post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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Baseline (pre-treatment, i.e. 1 week after recruitment), post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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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.
Time Frame: 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)
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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)
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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.
Time Frame: Baseline (pre-treatment, i.e. 1 week after recruitment), post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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Baseline (pre-treatment, i.e. 1 week after recruitment), post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Andreas Lutterotti, Prof. Dr. med., Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
October 14, 2019
Primary Completion (ACTUAL)
December 27, 2019
Study Completion (ACTUAL)
December 27, 2019
Study Registration Dates
First Submitted
February 14, 2019
First Submitted That Met QC Criteria
March 4, 2019
First Posted (ACTUAL)
March 5, 2019
Study Record Updates
Last Update Posted (ACTUAL)
March 30, 2021
Last Update Submitted That Met QC Criteria
March 25, 2021
Last Verified
March 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 201802353
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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