UMIN-CTR Clinical Trial

Basic information
Public title	An exploratory clinical trial on the effectiveness and safety of skin electrical stimulation for Leber hereditary optic neuropathy
Acronym	A clinical trial of skin electrical stimulation for Leber hereditary optic neuropathy
Scientific Title	An exploratory clinical trial on the effectiveness and safety of skin electrical stimulation for Leber hereditary optic neuropathy
Scientific Title:Acronym	A clinical trial of skin electrical stimulation for Leber hereditary optic neuropathy
Region	Japan

Condition
Condition	Leber hereditary optic neuropathy
Classification by specialty	Ophthalmology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	Leber hereditary optic neuropathy (LHON) is a disease, in which retinal ganglion cells falls into apoptotic cell death due to mainly one of three point mutations of mitochondrial DNA (mtDNA) at nucleotide positions 3460, 11778, 14484, characterized by acute or subacute vision loss of bilateral eyes with an inter-eye time lag in predominantly young males of second to fourth decade of life. Since LHON causes serious impairment of the central vision bilaterally and no effective treatment has been established, the development of a novel therapeutic approach is urgent. We will conduct an exploratory clinical trial to examine the effectiveness and safety of electric stimulation using skin electrical stimulation (SES) device for the improvement of the visual dysfunction in LHON patients. The clinical significance will be extremely high if the improvement of visual function is obtained by SES that can be easily and safely carried out.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Not applicable

Assessment
Primary outcomes	LogMAR visual acuity at 1 week after six consecutive skin electrical stimulation (once every two weeks for 10 weeks).
Key secondary outcomes	1. LogMAR visual acuity at 4 and 8 week after six consecutive skin electrical stimulation (once a week for 6 weeks). 2. Mean deviation and pattern standard deviation in Humphrey static visual field test (center 30-2, stimulus size 3 or 5), Foveal threshold value, total, the number of 1% and 5% of probability plot with pattern deviation 3. The value of critical fusion frequency 4. Color vision test (standard Pseudoisochromatic Plates Part 2 for Aquired Color Vision Defects (SPP-2)) 5. Thickness of peripapillary retinal nerve fiber and macular retinal ganglion cell complex detected by optical coherence tomography 6. The sensitivity of central visual field detected by Micrometry (MP-3) 7. The amplitude of visual evoked potential (Multifocal VEP)

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification	NO
Dynamic allocation	NO
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Device,equipment
Interventions/Control_1	Skin electrical stimulation (SES), The number of intervention is six times (single SES every two weeks for 10 weeks)
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	16 years-old <=
Age-upper limit	80 years-old >
Gender	Male and Female
Key inclusion criteria	Inclusion criteria Subjects should fulfill all conditions as follows: 1. Patients with ages ranging from 16 and 80 years of age. 2. Patients who provide written informed consent. In cases under 20 years, informed consent must be obtained from both patients themselves and guardians. 3. Patients with the disease more than 8 months since onset without visual improvement. 4. Patients with a missense mutation of mtDNA at the positon 11778. 5. Patients who show best corrected decimal visual acuity less than 0.1.
Key exclusion criteria	Exclusion criteria Patients who have at least one condition as below will be excluded. 1. Patients who had smoked until the last half of year 2. Patients with implantable electronic devices such as cardiac pacemakers etc. 3. Patients with a history of intraocular surgery within the past a year 4. Patients with other eye diseases except for the eyes with incipient cataract or intraocular lens 5. Patients who use idebenone and have past history of administration of idebenone within 1 year 6. Patients who use either ethambutol, chloramphenicol, linezolid, erythromycin, streptomycin, antiretroviral drugs, amiodarone, infliximab, clioquinol, dapsone, quinine, pheniprazine, suramin sodium, or isoniazid. 7. Patients with a history of epilepsy 8. Pregnant individuals 9. Patients with severe allergic diseases including atopic dermatitis 10. Patients participating in other clinical studies 11. Patients judged inappropriate for other research responsible doctors
Target sample size	11

Research contact person
Name of lead principal investigator	1st name Middle name Last name Takuji Kurimoto
Organization	Kobe University Graduate School of Medicine
Division name	Ophthalmology
Zip code
Address	7-5-2 Kusunoki-cho Chuo-ku Kobe
TEL	078-382-5111
Email	kuri1201@med.kobe-u.ac.jp

Public contact
Name of contact person	1st name Middle name Last name Takuji Kurimoto
Organization	Kobe University Graduate School of Medicine
Division name	Ophthalmology
Zip code
Address	7-5-2 Kusunoki-cho Chuo-ku Kobe
TEL	078-382-5111
Homepage URL
Email	kuri1201@med.kobe-u.ac.jp

Sponsor
Institute	Department of Surgery, Devision of Ophthalmology, Kobe University Graduate School of Medicine
Institute
Department

Funding Source
Organization	Department of Surgery, Devision of Ophthalmology, Kobe University Graduate School of Medicine
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2018 Year 04 Month 01 Day

Related information
URL releasing protocol
Publication of results	Published

Result
URL related to results and publications
Number of participants that the trial has enrolled	11
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Main results already published
Date of protocol fixation	2018 Year 03 Month 20 Day
Date of IRB	2018 Year 03 Month 20 Day
Anticipated trial start date	2018 Year 03 Month 28 Day
Last follow-up date	2019 Year 09 Month 01 Day
Date of closure to data entry	2020 Year 03 Month 31 Day
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2018 Year 01 Month 30 Day
Last modified on	2020 Year 08 Month 02 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035434