Transcorneal Electrical Stimulation for the Treatment of Retinitis Pigmentosa - a Safety and Efficacy Multicenter Study (TES/RP)

Transcorneal Electrical Stimulation for the Treatment of Retinitis Pigmentosa - a Safety and Efficacy NSR Device Study - A Multicenter Study

Several studies have shown that TES in RP patients may help to slow the progressive deterioration of this degenerative disease. The end point of this clinical trial is to slow or stop disease progression with weekly treatment using TES for 1 year.

Study Overview

• Status: Withdrawn
• Conditions: Retinitis Pigmentosa
• Intervention / Treatment: Device: Transcorneal Electrical Stimulation using Okustim device

Detailed Description

The following proposed study (ICM1TES/RP) will investigate the therapeutic aspects of transcorneal electrical stimulation (TES) on the eye in patients with retinitis pigmentosa (RP). It will utilize the Okuvision TES system, a Wills Eye Hospital-sponsored FDA non-significant risk (NSR) medical device, OkuStim® (CE-marked OkuStim®) for the application of electrical stimulation directly to the eye via a corneal contact electrode.

Study Design - Multi-center, prospective, randomized sham controlled 1:1 Clinical trial.

Study treatments - Patients will be randomized in a 1:1 ratio. Patients in treatment group will have TES at 200% of phosphene threshold for 30 minutes once weekly for 52 weeks in both eyes. Patients in sham group will also wear electrodes on both eyes, but no energy is turned on and both eyes are sham.

Duration of study - anticipated duration is 36 months, 12 months for recruitment, 12 months for treatment and sham groups and followed for 18 months, plus 6 months for analysis.

Inclusion Criteria - Diagnosis of RP, 22-80 years of age, no other ocular disease, able to complete all visits.

Treatments - TES, 30 minute treatment weekly for 52 weeks at 0.8mA

Number of patients - 90 patients in treatment arm and 90 patients in sham arm. Electrodes will be placed on both eyes, both eyes will be treated in treatment group and in the sham group both eyes will be considered. However due to the possibility of drop out using 15% we will recruit 210 patients (15 patients per center).

Screening -

1. VA & Phosphene threshold evaluation
2. Vfiii4e, vfVe, Octopus 900, complete eye exam, fundus photo, OCT and Contrast sensitivity, electro-physiology.
3. Eligibility requirements met, then schedule baseline.

Tests - Base Line: VA, vfiii4e, vfVe, Octopus 900, complete eye exam, fundus photo, OCT, Contrast sensitivity, NEI VFQ-25, Photopic B-wave ERG, blood draw for genetic test (unless genetic profile has been done).

3 Month visit: VA, eye exam, Phosphene threshold, OCT & Photopic B-wave.

6 Month visit: VA, vfiii4e, vfVe, Octopus 900, complete eye exam, OCT & Contrast sensitivity, phosphine threshold & Photopic B-wave.

9 Month visit: VA, eye exam, Phosphene threshold, OCT & Photopic B-wave.

12 Month visit: VA, vfiii4e, vfVe, Octopus 900, complete eye exam, OCT & Contrast sensitivity, NEI VFQ-25, phosphene threshold & Photopic B-wave

18 Month visit: VA, vfiii4e, vfVe, Octopus 900, complete eye exam, OCT & Contrast sensitivity, NEI VFQ-25 & phosphene threshold & Photopic B-wave.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Wills Eye Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with Retinitis Pigmentosa.
2. Adult patients, 22-80 years of age, having provided written informed consent and HIPAA authorization.
3. LogMAR VA 1.00 or better in both eyes.
4. Octopus 900 Central Visual Field ≥10 degrees diameter around central fixation using stimulus sizes III4e and V4e in both eyes on kinetic testing.
5. Agree to discontinue Vitamin A use and no intake for at least 2 months prior to baseline visit.

Exclusion Criteria:

1. Visual field loss as demonstrated by Octopus 900 kinetic perimetry as <10 deg of remaining central visual field using stimulus sizes III4e and V4e.
2. Due to distance or other reason, patients unable to travel to Philadelphia or respective centers for the treatment procedures and follow-up examinations.
3. Diabetic retinopathy
4. Ocular neovascularisation of any origin
5. After arterial or venous occlusion
6. After retinal detachment or any vitreoretinal surgery with or without implantation.
7. Silicone oil tamponade
8. Dry or exudative age-related macular degeneration
9. Macular edema involving the foveal center as determined by SD-OCT
10. All forms of glaucoma
11. Any form of corneal degeneration that reduces visual acuity
12. Systemic diseases that are difficult to control or manage, which could hinder regular attendance at follow-up examinations
13. Patients in a permanently poor general condition, which could hinder regular attendance at follow-up examinations
14. Patients in whom phosphenes are only inducible at greater than, but not including, 0.8 mA.
15. Forms of mental illness related to the bipolar affective and schizoid-affective disorders, epilepsy, and all forms of dementia
16. Simultaneous participation in another interventional study or history of interventions whose effect may still persist
17. Current pregnancy, or being a woman with childbearing potential who is unwilling to use medically acceptable means of birth control for the study duration, or a woman unwilling to perform a pregnancy test at study entry
18. Any patient can be excluded from the study as determined by the Principal Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; Subjects in the treatment group will undergo bilateral transcorneal electrical stimulation using OkuStim device once a week for fifty-two weeks	Device: Transcorneal Electrical Stimulation using Okustim device; The Okustim® stimulation device is a battery-powered electronic neuro-stimulator, which delivers a weak electrical pulse. This current is delivered to the eyes by the OkuStim® device using the "OkuEl®" electrodes, which are held in place via the "OkuSpex®" frame. In this study the treatment level will be held constant at 0.8 mA for all study subjects. After switching on the neuro-stimulator, the subject's retina will be stimulated through specific electrodes (OkuEl, held in position by the OkuSpex) worn on the face with the predetermined intensity and time period (delivered by the OkuStim device).
Placebo Comparator: Sham group; Subjects in the Sham group will wear the OkuSpex and OkuEl (applied to cornea upon the lower lid) and be attached to the OkuStim device in the same manner as the treatment group, but will receive no electrical stimulation for the 30 minutes that the TES fiber is applied to the cornea (even though the device has been turned on) once a week for fifty-two weeks	Device: Transcorneal Electrical Stimulation using Okustim device; The Okustim® stimulation device is a battery-powered electronic neuro-stimulator, which delivers a weak electrical pulse. This current is delivered to the eyes by the OkuStim® device using the "OkuEl®" electrodes, which are held in place via the "OkuSpex®" frame. In this study the treatment level will be held constant at 0.8 mA for all study subjects. After switching on the neuro-stimulator, the subject's retina will be stimulated through specific electrodes (OkuEl, held in position by the OkuSpex) worn on the face with the predetermined intensity and time period (delivered by the OkuStim device).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Octopus vfiii4e (Progressive slowing of Visual Field deterioration)	Octopus vfiii4e test will be done at Screening visit, Baseline visit, Week 26, Week 53 and Week 76 to analyze progressive slowing of Visual Field deterioration	76 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual acuity (VA)	VA testing will be done at all visits	76 weeks
Contrast sensitivity	Contrast sensitivity testing will be done at Baseline visit, Week 26, Week 53 and Week 76	76 weeks
NEI-VFQ-25 total score & subscores	NEI-VFQ-25 survey will be filled out at Baseline visit and at Week 53	53 weeks
Photopic b-wave ERG	Photopic b-wave ERG test will be done at Baseline visit, Week 13, Week 26, Week 39, Week 53 and Week 76	76 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in phosphene threshold detection levels	Change in phosphene threshold detection levels will be done at Screening visit, Baseline visit, Week 13, Week 26, Week 39, Week 53 and Week 76. This is an exploratory efficacy endpoint.	76 weeks
Octopus GATE (static)	Octopus GATE (static) test will be done at Screening visit, Baseline visit, Week 26, Week 53 and Week 76. This is an exploratory efficacy endpoint.	76 weeks
Octopus vf V4e (kinetic)	Octopus vf V4e (kinetic) test will be done at Screening visit, Baseline visit, Week 26, Week 53 and Week 76. This is an exploratory efficacy endpoint.	76 weeks
SD-OCT (ez analysis)	SD-OCT (ez analysis) test will be done at Screening visit, Baseline visit, Week 26, Week 53 and Week 76. This is an exploratory efficacy endpoint.	76 weeks

Collaborators and Investigators

• Sponsor: Wills Eye
• Collaborators: Okuvision GmbH
• Investigators: Study Director: Leslie Hyman, PhD, Wills Eye Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2019
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: September 9, 2015
• First Submitted That Met QC Criteria: September 11, 2015
• First Posted (Estimate): September 14, 2015

Study Record Updates

• Last Update Posted (Actual): May 1, 2019
• Last Update Submitted That Met QC Criteria: April 29, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: RP; Retinitis Pigmentosa; TES; Transcorneal Electrical Stimulation
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Retinal Dystrophies; Retinitis; Retinitis Pigmentosa
• Other Study ID Numbers: IMC1TES/RP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes