UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000017939 |
|---|---|
| Receipt number | 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 | 2020/12/20 09:57:47 |
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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
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
ohmyeye@hyo-med.ac.jp
Sponsor or person
Institute
Hyogo College of Medicine
Institute
Department
Personal name
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
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
https://link.springer.com/article/10.1007/s10384-020-00789-2
Publication of results
Published
Result
URL related to results and publications
https://link.springer.com/article/10.1007/s10384-020-00789-2
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
Results Delay Reason
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
Completed
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
| 2020 | Year | 12 | Month | 20 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000020747
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