search
Back to results

Repetitive Transorbital Alternating Current Stimulation in Acute Autoimmune Optic Neuritis (ACSON)

Primary Purpose

Acute Autoimmune Inflammatory Optic Neuritis

Status
Terminated
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
active-rtACS treatment
sham-rtACS treatment
Sponsored by
University of Zurich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Autoimmune Inflammatory Optic Neuritis focused on measuring optic neuritis, multiple sclerosis, repetitive transorbital alternating current stimulation, optical coherence tomography, low-contrast visual acuity

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Neurology and Department of Ophthalmology, University Hospital Zurich

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

active-rtACS arm

sham-rtACS arm

Arm Description

Active rtACS on 10 consecutive working days, in addition to standard-of-care corticosteroid treatment.

Sham rtACS on 10 consecutive working days, in addition to standard-of-care corticosteroid treatment.

Outcomes

Primary Outcome Measures

The primary functional outcome measure will be low-contrast visual acuity [LogMAR] at 16 weeks (3 month follow-up) in ON eyes.
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).
The primary safety outcome measure will be the total number of adverse events during the entire study period

Secondary Outcome Measures

Low-contrast visual acuity [LogMAR] at 4 (post-treatment) weeks in ON eyes.
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).
High-contrast visual acuity [LogMAR] at 16 weeks (3 month follow-up) in ON eyes.
High-contrast visual acuity [LogMAR] at 4 weeks (post-treatment) in ON eyes.
Colour vision [tritan] at 16 weeks (3 month follow-up) in ON eyes.
Colour vision [tritan] at 4 weeks (post-treatment) in ON eyes.
Visual field testing [dB] at 16 weeks (3 month follow-up) in ON eyes.
Visual field testing [dB] at 4 weeks (post-treatment) in ON eyes.
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).
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).
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.
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).
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.
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.
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.
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.

Full Information

First Posted
February 14, 2019
Last Updated
March 25, 2021
Sponsor
University of Zurich
Collaborators
University Hospital, Zürich, Swiss MS Society, Data Management, Clinical Trials Center, Zurich, Switzerland
search

1. Study Identification

Unique Protocol Identification Number
NCT03862313
Brief Title
Repetitive Transorbital Alternating Current Stimulation in Acute Autoimmune Optic Neuritis
Acronym
ACSON
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Terminated
Why Stopped
Primarily due to insufficient recruitment (n = 2 instead of n = 30), the study was prematurely discontinued for feasibility reasons. Neither any meaningful results on safety nor on efficacy can be reported.
Study Start Date
October 14, 2019 (Actual)
Primary Completion Date
December 27, 2019 (Actual)
Study Completion Date
December 27, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Zurich
Collaborators
University Hospital, Zürich, Swiss MS Society, Data Management, Clinical Trials Center, Zurich, Switzerland

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Autoimmune Inflammatory Optic Neuritis
Keywords
optic neuritis, multiple sclerosis, repetitive transorbital alternating current stimulation, optical coherence tomography, low-contrast visual acuity

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
active-rtACS arm
Arm Type
Experimental
Arm Description
Active rtACS on 10 consecutive working days, in addition to standard-of-care corticosteroid treatment.
Arm Title
sham-rtACS arm
Arm Type
Sham Comparator
Arm Description
Sham rtACS on 10 consecutive working days, in addition to standard-of-care corticosteroid treatment.
Intervention Type
Device
Intervention Name(s)
active-rtACS treatment
Other Intervention Name(s)
NextWave® 1.1 system, EBS Technologies GmbH, Germany
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
sham-rtACS treatment
Other Intervention Name(s)
NextWave® 1.1 system, EBS Technologies GmbH, Germany
Intervention Description
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.
Primary Outcome Measure Information:
Title
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)
Title
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)
Title
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)
Secondary Outcome Measure Information:
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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)
Title
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).
Description
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.
Time Frame
3 month follow-up (16 weeks after recruitment, i.e. 3 months after the last treatment day)
Title
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).
Description
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.
Time Frame
post-treatment (4 weeks after recruitment, i.e. one week after the last treatment day)
Title
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)
Title
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)
Title
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)
Title
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)

10. Eligibility

Sex
All
Gender Based
Yes
Gender Eligibility Description
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 continuously in an unbiased fashion, gender might become relevant in an advanced phase of the study (e.g. if the female block has already been fully recruited and only males might still be enrolled). As female preponderance is a well-known fact in multiple sclerosis, the investigators anticipate that approximately 2/3 of the patients will be females.
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreas Lutterotti, Prof. Dr. med.
Organizational Affiliation
Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Neurology and Department of Ophthalmology, University Hospital Zurich
City
Zurich
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Repetitive Transorbital Alternating Current Stimulation in Acute Autoimmune Optic Neuritis

We'll reach out to this number within 24 hrs