Protocol to test the efficacy and safety of frequent applications of skin electrical stimulation for Leber hereditary optic neuropathy: a single-arm, open-label, non-randomised prospective study

Abstract

Introduction: Leber hereditary optic neuropathy (LHON) is an acute or subacute inherited optic neuropathy caused by mitochondrial mutations. More than 90% of patients with LHON have one of three point mutations (ie, G3460A, G11778A and T14484C). We previously reported that a 12-week session of skin electrical stimulation (SES) with a 2-week interval significantly improved visual acuity and field tests 1 week after the last stimulation and without adverse effects in 10 cases of LHON carrying the mt DNA G11778A mutation. In the present study, we will examine the magnitude and persistence of the efficacy and presence or absence of adverse events using SES with a more frequent stimulation protocol.

Methods and analysis: This study will be a single-arm, open-labelled, non-randomised clinical study that analyses 15 cases of LHON with G11778A mutation. All participants will take a portable SES device home and perform SES by themselves every other day for 12 weeks. The logarithm for the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) at 1 week after the last SES will be measured as the primary outcome. LogMAR BCVA will be measured at four and 8 weeks after the last SES treatment. The Humphrey visual field sensitivity test using size V stimulation and critical fusion frequency at 1, 4 and 8 weeks after the last SES session will be secondary outcome measurements. Slit-lamp examination, optical coherence tomography and specular microscopy will also be performed to verify the safety of SES.

Ethics and dissemination: The protocol was approved by the Institutional Review Board at Kobe University, Japan (Approval No.C190030). This study is in progress and deserves Pre-result. All documents communicating with the ethics committee will be reposited by the researcher. Modifications to the protocol will be reviewed by the ethics committee and implemented after approval. Data monitoring will be performed by a researcher who is not involved in the study every 6 months after approval. The research summary results will be registered in the Japan Registry of Clinical Trials (jRCTs) and made available to participants in accordance with the terms described in the documents. In addition, the results of this study will be presented at domestic and international meetings and published in peer-reviewed journals within a year after data is fixed.

Trial registration number: jRCTs052200033.

Keywords: clinical trials; neuro-ophthalmology; neurogenetics.

Figure 1

The portable device used for skin electrical stimulation. Each number indicates the components of the portable device. ① the button for the selection of the stimulated eye: R, right eye, RL, both eyes, L, left eye. ② The button for the emergency stop. ③ The power indicator. ④ Adjustment knob for the amount of current. ⑤ The menu button to manipulate the conditions of electrical stimulation. ⑥ The button to start electrical stimulation. ⑦ The pause button to temporarily stop electrical stimulation. If the button is hit once more, electrical stimulation will restart from the time point of the pause.

Figure 2

Study flow chart.