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Recruitment status No longer recruiting
Unique ID issued by UMIN UMIN000017939
Receipt No. R000020747
Scientific Title Multicenter study of therapeutic effects of Idebenone in patients with Leber hereditary optic neuropathy
Date of disclosure of the study information 2015/06/20
Last modified on 2019/12/20

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Basic information
Public title Multicenter study of therapeutic effects of Idebenone in patients with Leber hereditary optic neuropathy
Acronym Clinical trial of Idebenone in patients with LHON
Scientific Title Multicenter study of therapeutic effects of Idebenone in patients with Leber hereditary optic neuropathy
Scientific Title:Acronym Clinical trial of Idebenone in patients with LHON
Region
Japan

Condition
Condition Leber hereditary optic neuropathy
Classification by specialty
Ophthalmology
Classification by malignancy Others
Genomic information YES

Objectives
Narrative objectives1 Leber hereditary optic neuropathy (LHON) is caused by mitochondrial DNA point mutations, presenting clinically an acute onset of visual loss. There is no effective therapies in patients with LHON that the 3 mitochondrial mutations (3460G>A, 11778G>A, 14484T>C) account for over 90% of cases. The mitochondrial mutations may lead to inhibit ATP synthesis in the mitochondria, resulting retinal ganglion cells death and the optic nerve atrophy or neuropathy.
Idebenone was investigated by Takeda Pharmaceutical Company Limited in Japan for dementia, cerebral infarction sequelae and Alzheimer's disease in 1986. Idebenone may be suitable logically as a medicine for mitochondrial disease, because Idebenone have effects of the metabolic improvement in the mitochondria and the protection of mitochondrial inner membrane. Actually, Angebault C and colleagues reported in vitro study that Idebenone affected the fibroblasts derived from patients with LHON, to increase the activity of mitochondrial complex I.
Recently, in vivo study showed that Idebenone had neuroprotective effects in animal models of LHON, and some pilot studies suggested Idebenone had the therapeutic effects in patients with LHON. Furthermore, the big cohort study (103 cases) and the randomized prospective study (RHODOS: 85 cases) showed that Idebenone improved the visual acuity in patients with LHON, especially in cases at the initial stage of onset.
In the present study, we investigate the therapeutic effects of Idebenone in patients with LHON, contributing both the quality of life and vision to patients with LHON.
Basic objectives2 Safety,Efficacy
Basic objectives -Others
Trial characteristics_1 Confirmatory
Trial characteristics_2 Pragmatic
Developmental phase Phase I,II

Assessment
Primary outcomes Visual acuity (at 12 months after the start of the study drug)
Key secondary outcomes Visual acuity (at 6 months after the start of the study drug), Visual field (at 6 and 12 months after the start of the study drug), Critical flicker frequency (at 6 and 12 months after the start of the study drug), central retinal thickness (at 6 and 12 months after the start of the study drug)

Base
Study type Interventional

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

Intervention
No. of arms 1
Purpose of intervention Treatment
Type of intervention
Medicine
Interventions/Control_1 1. Clinical trial medicine: Idebenone 900mg/day
2. Objectives: 50 patients with LHON
3. Exclusion criteria:
a) A smoker
b) A patient with abnormality of hepatic function
c) A patient who present seizures, delirium and hallucination
d) Pregnancy or Lactation
e) A patient who is associated with agranulocytosis
f) A patient with chronic renal failure
g) A patient with anaphylactic shock against Idebenone
4. Duration of drug administration: 6 months
5. Examinations schedules: Both subjective and objective examinations are performed as following schedules;
a) At the base line: Visual acuity (VA), Critical flicker frequency (CFF), Visual field (VF: Humphry 30-2), central retinal thickness (CRT), functional MRI (f-MRI), searching the mitochondrial mutation
b) 8 weeks: VA, CFF, VF, CRT, f-MRI
c) 16 weeks: VA, CFF, VF, CRT, f-MRI
d) 24 weeks: VA, CFF, VF, CRT, f-MRI
e) 32 weeks: VA, CFF, VF, CRT, f-MRI
f) 40 weeks: VA, CFF, VF, CRT, f-MRI
g) 48 weeks: VA, CFF, VF, CRT, f-MRI
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
10 years-old <=
Age-upper limit
80 years-old >=
Gender Male and Female
Key inclusion criteria 50 patients with LHON
Key exclusion criteria a) A smoker
b) A patient with abnormality of hepatic function
c) A patient who present seizures, delirium and hallucination
d) Pregnancy or Lactation
e) A patient who is associated with agranulocytosis
f) A patient with chronic renal failure
g) A patient with anaphylactic shock against Idebenone
Target sample size 50

Research contact person
Name of lead principal investigator
1st name Hiroto
Middle name
Last name Ishikawa
Organization Hyogo College of Medicine
Division name Ophthalmology
Zip code 6638501
Address 1-1, Mukogawa-cho, Nishinomiya, Hyogo, Japan 663-8501
TEL 0798-45-6462
Email ohmyeye@hyo-med.ac.jp

Public contact
Name of contact person
1st name Hiroto
Middle name
Last name Ishikawa
Organization Hyogo College of Medicine
Division name Ophthalmology
Zip code 6638501
Address 1-1, Mukogawa-cho, Nishinomiya, Hyogo, Japan 663-8501
TEL 0798-45-6462
Homepage URL
Email ohmyeye@hyo-med.ac.jp

Sponsor
Institute Hyogo College of Medicine
Institute
Department

Funding Source
Organization Hyogo College of Medicine
Organization
Division
Category of Funding Organization Self funding
Nationality of Funding Organization

Other related organizations
Co-sponsor Kitasato University
Jikei University School of Medicine
Tokyo Medical University
Name of secondary funder(s)

IRB Contact (For public release)
Organization IRB, Hyogo College of Medicine
Address 1-1, Mukogawa-cho, Nishinomiya
Tel +81798456066
Email rinri@hyo-med.ac.jp

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 兵庫医科大学病院(兵庫県)

Other administrative information
Date of disclosure of the study information
2015 Year 06 Month 20 Day

Related information
URL releasing protocol
Publication of results Partially published

Result
URL related to results and publications
Number of participants that the trial has enrolled 57
Results
Almost 30% of patients with LHON who received LHON for 6 months improved their visual function.
Results date posted
2019 Year 12 Month 20 Day
Results Delayed
Delay expected
Results Delay Reason The manuscript is under submit.
Date of the first journal publication of results
Baseline Characteristics
Mean patient age was 28.9 years. Patients were predominantly male (52 cases, 91.2%) and 54 cases (94.7%) had a mt. 11778 G>A mutation. The time after disease onset was 6.4 years. There were 25 patients (43.9%) in whom more than one year had passed since disease onset. When patients presented disease onset, 35 patients (61.4%) developed unilaterally, and then all patients developed bilaterally 10.5 weeks after the onset.
Participant flow
In the present study, three patients dropped-out prematurely because they reported no favourable therapeutic effects of the study drug. Thus, we evaluated safety and tolerability in the remaining 54 patients. We selected patients with mitochondrial mutation 11778 for further analyses; therefore, 51 patients were analysed.
Adverse events
Those 54 patients completed the study and none showed any clinically significant adverse events, as categorized by the Common Terminology Criteria for Adverse Events ver. 4.0 (grade 3 or more) for vital signs, clinical symptoms and other biochemical and haematological parameters.
Outcome measures
For the primary end-point (percentage of patients with BCVA improvement at 48 weeks), significant improvement at least one eye was observed in 17 patients (33.3%), whereas worsened BCVA was observed in 15 (29.4%). In addition, significant improvement was observed in 13 patients (25.5%) at 24 weeks, whereas worsened BCVA was observed in 16 (31.4%) at that time. The mean of the BCVA values for all eyes at baseline, 24 weeks and 48 weeks were 1.441, 1.47 and 1.442 logMAR, respectively.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status No longer recruiting
Date of protocol fixation
2013 Year 10 Month 01 Day
Date of IRB
2013 Year 09 Month 10 Day
Anticipated trial start date
2013 Year 10 Month 01 Day
Last follow-up date
2017 Year 09 Month 30 Day
Date of closure to data entry
2017 Year 09 Month 30 Day
Date trial data considered complete
2017 Year 09 Month 30 Day
Date analysis concluded
2017 Year 09 Month 30 Day

Other
Other related information

Management information
Registered date
2015 Year 06 Month 17 Day
Last modified on
2019 Year 12 Month 20 Day


Link to view the page
URL(English) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000020747

Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name


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