A study protocol for evaluating the efficacy and safety of skin electrical stimulation for Leber hereditary optic neuropathy: a single-arm, open-label, non-randomized prospective exploratory study

Abstract

Background: Leber hereditary optic neuropathy (LHON) is a maternally inherited disease caused by three missense mutations of mitochondrial (mt) DNA, ie, m 3460 G>A, m 11778 G>A, or m 14484 T>C in the greater portion of LHON. m 11778 G>A mutation is especially observed in >90% of the cases in Japanese families. Although spontaneous remission of visual function infrequently occurs, effective treatment for LHON remains unestablished. Transcorneal electrical stimulation has been shown to be efficacious in individuals with optic neuropathy. However, due to potential risk of corneal damage, repeated treatments are not permissible. In this exploratory study, we will be conducting skin electrical stimulation (SES) as an intervention for patients with LHON having 11778 missense mutation and investigate effectiveness and safety of SES.

Methods: This is a single-arm, prospective, open-label exploratory trial focused on patients with LHON having 11778 missense mutation. Eleven patients will be enrolled and receive six consecutive SES once every 2 weeks up to 10 weeks. The safety of the SES will be monitored with specular microscopy, slit-lamp biomicroscopy, fundus examinations, and the observation of facial skin. The primary outcome measure will be the averaged l ogarithm of minimum angle resolution (logMAR) converted visual acuity 1 week after the last SES. Secondary outcome measures include changes, in logMAR at 4 and 8 weeks after the last SES, such as visual field indices measured using Humphrey visual field and microperimetry-3, the thickness of peripapillary retinal fiber and macular ganglion cell complex, multifocal visual evoked potentials, critical flicker frequency, and color vision.

Discussion: The results of this proposed proof-of-concept feasibility trial will help plan and execute a larger definitive trial to test SES as an effective strategy for LHON and related optic neuropathies and help establish a beneficial treatment for LHON.

Keywords:

• skin electrical stimulation
• Leber hereditary optic neuropathy
• logarithm of minimum angle resolution
• single-arm study

Abbreviation list

LogMAR, logarithm of minimum angle resolution; SES, skin electrical stimulation; BCVA, best corrected visual acuity; mtDNA, mitochondrial DNA; LHON, Leber hereditary optic neuropathy; TES, Transcorneal electrical stimulation; HVF, Humphrey visual field; CFF, critical fusion frequency; MP-3, microperimetry-3; cpRNFL, circumpapillary retinal nerve fiber layer; GCC, ganglion cell complex; OCT, Optical coherence tomography.

Availability of data and material

Data from the trial will be made available for the institutional policies.

Consent for publication

The consent for publication will be obtained from eligible patients before they participate in the trial.

Ethics approval and consent to participate

The present study’s protocol received approval from the Institutional Review Board at Kobe University, Japan (approval No. 290080) and will be conducted in accordance with the current Declaration of Helsinki. Eligible patients will undergo informed consent before participating in the trial.

Author contributions

TK and MN contributed to the study concept. KU contributed to the analytic plan. SM and TK drafted the first paper and wrote revision and the final manuscript. All authors made substantial contributions to the concept and design of the trial. All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.