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

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ClinicalTrials.gov Identifier: NCT03862313
Recruitment Status : Recruiting
First Posted : March 5, 2019
Last Update Posted : February 17, 2020
Sponsor:
Collaborators:
University Hospital, Zürich
Swiss MS Society
Data Management, Clinical Trials Center, Zurich, Switzerland
Information provided by (Responsible Party):
University of Zurich

Tracking Information
First Submitted Date  ICMJE February 14, 2019
First Posted Date  ICMJE March 5, 2019
Last Update Posted Date February 17, 2020
Actual Study Start Date  ICMJE October 14, 2019
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 4, 2019)
  • 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) ]
  • 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) ]
  • 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) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2019)
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
    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). [ Time Frame: 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. [ 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Repetitive Transorbital Alternating Current Stimulation in Acute Autoimmune Optic Neuritis
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Acute Autoimmune Inflammatory Optic Neuritis
Intervention  ICMJE
  • Device: active-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.
    Other Name: NextWave® 1.1 system, EBS Technologies GmbH, Germany
  • Device: sham-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.
    Other Name: NextWave® 1.1 system, EBS Technologies GmbH, Germany
Study Arms  ICMJE
  • Experimental: active-rtACS arm
    Active rtACS on 10 consecutive working days, in addition to standard-of-care corticosteroid treatment.
    Intervention: Device: active-rtACS treatment
  • Sham Comparator: sham-rtACS arm
    Sham rtACS on 10 consecutive working days, in addition to standard-of-care corticosteroid treatment.
    Intervention: Device: sham-rtACS treatment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 4, 2019)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Gender Based Eligibility: 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.
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Andreas Lutterotti, Prof. Dr. med. +41 44 255 49 84 Andreas.Lutterotti@usz.ch
Contact: Carla A Wicki, MSc +41 44 253 78 98 Carla.Wicki@usz.ch
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03862313
Other Study ID Numbers  ICMJE 201802353
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Zurich
Study Sponsor  ICMJE University of Zurich
Collaborators  ICMJE
  • University Hospital, Zürich
  • Swiss MS Society
  • Data Management, Clinical Trials Center, Zurich, Switzerland
Investigators  ICMJE
Principal Investigator: Andreas Lutterotti, Prof. Dr. med. Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
PRS Account University of Zurich
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP