Alternating and Direct Current Stimulation for Neuropathic Eye Pain

Alternating and Direct Current Stimulation for the Treatment of Chronic Neuropathic Eye Pain and Cerebral Symptoms: a Pilot Study

The goal of this clinical intervention is to test if two forms of transcranial current stimulation, transcranial direct current stimulation (tDCS) or transcranial alternating current stimulation (tACS) can alleviate neuropathic eye pain in a sample of 20 patients.

The main aims are:

• Test if tDCS/tACS can alleviate neuropathic eye pain and/or other cerebral symptoms: brain fatigue, migraine, light sensitivity, etc.
• Test if one stimulation method is superior to the other Patients will be treated for a total of fifteen 30-minute stimulation sessions, three times a day over a five-day period, each stimulation separated by approximately 4 hours, with either active tACS or tDCS over the scalp corresponding to primary sensory and motor areas.

The patients will have questionnaires to monitor subjective experiences and pupillometry before and after treatment to monitor experimental outcomes.

Study Overview

• Status: Recruiting
• Conditions: Eye Pain; Cerebral Injury; Neuropathy, Optic
• Intervention / Treatment: Device: DC-Stimulator Plus (NeuroConn GmbH, Germany); Device: Sooma direct current stimulator (Sooma, Finland)

Detailed Description

Brief Summary sufficient

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Neil Lagali, PhD; Phone Number: +4613286680; Email: neil.lagali@liu.se
• Study Contact Backup: Name: Magnus Thordstein, MD; Email: magnus.thordstein@liu.se

Study Locations

• Sweden
  • Other / Non-US
    • Linköping, Other / Non-US, Sweden, 58183
      • Recruiting
      • Eye Clinic, University Hospital in Linköping
      • Contact: Neil Lagali; Phone Number: +4613286680; Email: neil.lagali@liu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• persistent eye pain for at least 6 months
• average eye pain intensity of 4 or more on a 0-10 numerical rating scale
• naive to transcranial stimulation
• eye pain having neuropathic-like characteristics

Exclusion Criteria:

• contraindication to transcranial stimulation (i.e., pacemaker, cardioverter defibrillator, neuro-stimulation (brain or spinal cord), bone growth stimulations, indwelling blood pressure monitors, epilepsy, pregnancy)
• presence of ocular diseases that are the likely cause of pain (i.e., corneal and conjunctival scarring, corneal edema, uveitis, iris transillumination defects, etc.)
• current participation in another study with an investigational drug or device within one month prior to screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transcranial alternating current stimulation; Transcranial alternating current stimulation (tACS) device using 50x70 mm electrodes that are placed bilaterally between EEG coordinates C3/C5 for left hemisphere and C4/C6 for right hemisphere (corresponding to S1 and M1 of the eye). The alternating current electrodes are in-phase and have the same peak to peak stimulation 3mA, for 30 minutes duration at 10Hz. An impedance value under 15 ohms is required at all times to ensure patient comfort and safety.	Device: DC-Stimulator Plus (NeuroConn GmbH, Germany); Transcranial alternating current stimulation
Experimental: Transcranial direct current stimulation; Transcranial direct current stimulation (tDCS) device using 50x70 mm electrodes that has the anodal electrode placed contralateral to most prominent ocular pain or, in the case of bilateral pain symptoms, contralateral to the dominant hand between EEG coordinates C3/C5 for left hemisphere and C4/C6 for right hemisphere (corresponding to S1 and M1 of the eye), and the cathode placed on the patient's upper arm. A current peaking at 3mA will ramp up for 20 secs and be delivered for a total of 20 minutes, thereafter, ramping down for 20s. An impedance value under 15 ohms is required at all times to ensure patient comfort and safety.	Device: Sooma direct current stimulator (Sooma, Finland); Transcranial direct current stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline pupil diameter in millimeters at 1 week	Minimum and maximum pupil diameter in millimeters	through treament completion, 1 week
Change from baseline pupil velocity in millimeters per second at 1 week	Pupil change velocity in millimeters per second	through treament completion, 1 week
Change from baseline pupil latency in milliseconds at 1 week	Pupil latency latency in milliseconds	through treament completion, 1 week
Change from baseline subjective pain via neuropathic pain symptom inventory for the eye (NPSI-eye) at 1 week	Assesses pain related symptoms on a scale from 0 indicating no pain (better outcome) to10 indicating worst pain imaginable (worse outcome)	through treatment completion, 1 week
Change from baseline subjective pain via neuropathic pain symptom inventory for the eye (NPSI-eye) at 2 weeks	Assesses pain related symptoms on a scale from 0 indicating no pain (better outcome) to10 indicating worst pain imaginable (worse outcome)	through treatment completion, 2 weeks
Change from baseline subjective pain via neuropathic pain symptom inventory for the eye (NPSI-eye) at 1 month	Assesses pain related symptoms on a scale from 0 indicating no pain (better outcome) to10 indicating worst pain imaginable (worse outcome)	through treatment completion, 1 month
Change from baseline subjective pain effect experiences via Defense and Veteran Pain Rating Scale (DVPRS) at 1 week	Assesses pain related symptoms effecting sleep, stress, disposition, life quality, on a scale from 0 indicating no effect (better outcome) to10 indicating maximum effect (worse outcome)	through treatment completion, 1 week
Change from baseline subjective pain effect experiences via Defense and Veteran Pain Rating Scale (DVPRS) at 2 weeks	Assesses pain related symptoms effecting sleep, stress, disposition, life quality, on a scale from 0 indicating no effect (better outcome) to10 indicating maximum effect (worse outcome)	through treatment completion, 2 weeks
Change from baseline subjective pain effect experiences via Defense and Veteran Pain Rating Scale (DVPRS) at 1 month	Assesses pain related symptoms effecting sleep, stress, disposition, life quality, on a scale from 0 indicating no effect (better outcome) to10 indicating maximum effect (worse outcome)	through treatment completion, 1 month
Change from baseline subjective mental symptoms via Mental Fatigue Scale (MFS) at 1 week	Assesses mental symptoms on a scale from 0 indicating no effect (better outcome) to 3 indicating extreme effect (worse outcome)	through treatment completion, 1 week
Change from baseline subjective mental symptoms via Mental Fatigue Scale (MFS) at 2 weeks	Assesses mental symptoms on a scale from 0 indicating no effect (better outcome) to 3 indicating extreme effect (worse outcome)	through treatment completion, 2 weeks
Change from baseline subjective mental symptoms via Mental Fatigue Scale (MFS) at 1 month	Assesses mental symptoms on a scale from 0 indicating no effect (better outcome) to 3 indicating extreme effect (worse outcome)	through treatment completion, 1 month
Change from baseline subjective ocular symptoms and symptom frequency via custom ocular pain questionnaire at 1 week	Ocular pain questionnaire using a visual analog scale with 0 indicating no pain (better outcome) and 10 indicating extreme pain (worse outcome) and frequency measure from 0% indicating never occurring (better outcome) to 100% indicating always occurring (worse outcome)	through treatment completion, 1 week
Change from baseline subjective ocular symptoms and symptom frequency via custom ocular pain questionnaire at 2 weeks	Ocular pain questionnaire using a visual analog scale with 0 indicating no pain (better outcome) and 10 indicating extreme pain (worse outcome) and frequency measure from 0% indicating never occurring (better outcome) to 100% indicating always occurring (worse outcome)	through treatment completion, 1 month
Change from baseline subjective ocular symptoms and symptom frequency via custom ocular pain questionnaire at 1 month	Ocular pain questionnaire using a visual analog scale with 0 indicating no pain (better outcome) and 10 indicating extreme pain (worse outcome) and frequency measure from 0% indicating never occurring (better outcome) to 100% indicating always occurring (worse outcome)	through treatment completion, 1 month
Number of patients with treatment-related adverse events as assessed by ocular pain questionnaire	Ocular pain questionnaire using a visual analog scale with 0 indicating no pain (better outcome) and 10 indicating extreme pain (worse outcome) and frequency measure from 0% indicating never occurring (better outcome) to 100% indicating always occurring (worse outcome)	through treatment completion, 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment compliance rate	Evaluation of completed treatment from a total of 15	through study completion, 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beta coefficients for participant demographics (sex, age, race/ethnicity) in regression model predicting adherence to treatment protocol	Exploratory regression analysis to identify associations between demographic variables and number of treatment sessions completed	through study completion, 1 year
Beta coefficients for participant demographics (sex, age, race/ethnicity) in regression model predicting change in pain (Numerical Rating Scale)	Exploratory regression analysis to identify associations between demographic variables and change in pain ratings (before vs. after stimulation treatment)	through study completion, 1 year

Collaborators and Investigators

• Sponsor: Neil Lagali
• Collaborators: Linkoeping University
• Investigators: Principal Investigator: Neil Lagali, PhD, RegionÖstergötland

Publications and helpful links

General Publications

• Qazi Y, Hurwitz S, Khan S, Jurkunas UV, Dana R, Hamrah P. Validity and Reliability of a Novel Ocular Pain Assessment Survey (OPAS) in Quantifying and Monitoring Corneal and Ocular Surface Pain. Ophthalmology. 2016 Jul;123(7):1458-68. doi: 10.1016/j.ophtha.2016.03.006. Epub 2016 Apr 16.
• Farhangi M, Feuer W, Galor A, Bouhassira D, Levitt RC, Sarantopoulos CD, Felix ER. Modification of the Neuropathic Pain Symptom Inventory for use in eye pain (NPSI-Eye). Pain. 2019 Jul;160(7):1541-1550. doi: 10.1097/j.pain.0000000000001552.
• Sivanesan E, Levitt RC, Sarantopoulos CD, Patin D, Galor A. Noninvasive Electrical Stimulation for the Treatment of Chronic Ocular Pain and Photophobia. Neuromodulation. 2018 Dec;21(8):727-734. doi: 10.1111/ner.12742. Epub 2017 Dec 28.

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: June 16, 2023
• First Submitted That Met QC Criteria: June 26, 2023
• First Posted (Actual): July 5, 2023

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 4, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Pain; Neurologic Manifestations; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Cranial Nerve Diseases; Eye Manifestations; Brain Injuries; Optic Nerve Diseases; Eye Pain
• Other Study ID Numbers: 20220727401

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