Clinical trial NCT01267422: Safety and Efficacy Study of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy (LHON)
Official title: Safety and Efficacy Study of a Single Intravitreal Injection of rAAV2-ND4 Treatment of Leber Hereditary Optic Neuropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Leber Hereditary Optic Neuropathy
Keywords: Leber's Hereditary Optic Neuropathy,11778 LHON mutation,
rAAV2-ND4,triamcinolone acetonide
Lead sponsor: Huazhong University of Science and Technology
Sponsor class: OTHER
Collaborators: name: Huazhong University of Science and Technology
First posted: 2010-12-28
Enrollment: 9
Sex: ALL
Minimum age (years): 8
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is meant to assess the safety and efficacy of rAAV2-ND4 treatment of Leber hereditary optic neuropathy with 11778 LHON mutation.

Detailed description: Leber's Hereditary Optic Neuropathy (LHON) is a maternally inherited ocular disorder associated with a mutation in mtDNA . The common manifestation is visual loss which caused by the respiratory chain enzymes complex dysfunction resulting in increased oxidative stress enzymes production.

Material and Method Seven patients with 11778 LHON mutation were randomly treated with a Single IVT Injection of recombinant Adeno-Associated Virus-NADH dehydrogenase, subunit 4 (complex I)（rAAV2-ND4)（0.05ml).The dose was 5 × 10\^9 vg/0.05 mL for patients younger than 12 years old, and 1 × 10\^10 vg/0.05 mL for patients older than 12 years old. The visual acuity, visual evoked potential （VEP）,optical coherence tomography（ OCT）, computerized visual field, electroretinograms(ERG), retinal nerve fiber layer(RNFL)and Liver and kidney function in plasma were compared before and after treatment at 1,3,and 6, months interval.

Eligibility criteria: Inclusion Criteria:

1. comply with Leber hereditary optic neuropathy diagnostic criteria.
2. in patients with informed consent, voluntary participation.
3. signed informed consent.
4. 8 ≤ Age ≤ 60 years old, good health, the patient can tolerate local anesthesia surgery.
5. to comply with doctor's instructions, can in the time of referral.

Exclusion Criteria:

1. Cardiopulmonary and renal function in severe weakness, cancer, a variety of bleeding disorders, acute sensing disease, high fever, high fever disease, women during pregnancy, heart disease, such as post-operative recovery period.
2. Are participating in other clinical studies of patients.
3. Patients with mental disorders.

Primary outcomes:
measure: The Best Corrected Visual Acuity(BCVA)
timeFrame: Up to 3 years
measure: Results of CD3/CD4/CD8 Test
timeFrame: up to 6 months
Secondary outcomes:
measure: Intraocular Pressure;
timeFrame: Up to 3 years
measure: Neutralizing Antibody Assay
timeFrame: up to 3 years
measure: Average RNFL Thickness Througth Optical Coherence Tomography(OCT) Test
timeFrame: Up to 3 years
measure: Computerized Visual Field(MD: Mean Deviation, the Value Close to 0 Regarded Normal)
timeFrame: up to 3 years
measure: Computerized Visual Field(VFI: Visual Field Index ,the Value Close to 100% Regarded Normal)
timeFrame: up to 3 years
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Department of Ophthalmology ，Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
Study officials:
affiliation: Deputy Director of Ophthalmology
name: bin Li, PhD,MD
role: STUDY_CHAIR
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