Non-arteritic Ischemic Optic Neuropathy
Conditions
Keywords
Citicoline, Non-arteritic ischemic optic neuropathy, Neuroprotection, Neuroenhancement
Brief summary
The investigators tested the hypothesis whether the treatment with Citicoline in oral solution (OS-Citicoline) would increase or stabilize visual acuity, retinal ganglion cells (RGCs) function and neural conduction along the visual pathways (neuroenhancement), and/or induce preservation of RGCs fibers' loss (neuroprotection) in an human model of neurodegeneration: non-arteritic ischemic optic neuropathy (NAION).
Detailed description
The investigators enrolled 40 patients with bilateral or monolateral NAION and 20 age similar controls Twenty NAION patients received 500 mg/day of OS-Citicoline for a 6-months period followed by 3-months of wash-out (19 patients completed the study, NC Group); 20 NAION patients were not treated (19 patients completed the studyNN Group) from baseline up to 9 months. In all subjects, at baseline, at 6 and 9-months of follow-up: Visual acuity (VA), Pattern Electroretinogram (PERG), Visual Evoked Potentials (VEP), retinal nerve fiber layer thickness (RNFL-T) and Humphrey 24-2 visual field mean deviation (HFA MD) were assessed. Mean differences were statistically evaluated by ANOVA between Groups, and correlations were verified by Pearson's test.
Interventions
DIETARY_SUPPLEMENTCiticoline
Citicoline administered in oral solution
Sponsors
Fondazione G.B. Bietti, IRCCS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
1. Acute visual reduction episode from NAION occurring for more than 6 months 2. Typical defects of the visual field evidenced with the Goldmann perimetry or with Humphrey perimetry 30-2 3. Visual acuity not less than 1/10 4. Having suspended any potential neuroprotective therapies (e.g., Coenzyme Q10) for at least 6 months.
Exclusion criteria
* Ocular surgery in the 3 months preceding the study, including surgery for cataracts in the previous three months. * Cataract or maculopathy * Known hypersensitivity to the study product * Positive history for diseases of the optic nerve (retrobulbar optic neuropathy, glaucoma) or systemic diseases which could preclude the enrolment in the study according to the investigators' judgement * Pregnant or nursing women, or women of potential childbearing age not using adequate contraception. * Diabetes, SLE, rheumatoid arthritis, mixed connective tissue disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Visual Acuity at 9 Month | 9 months vs baseline | Increase of Visual Acuity evaluated by Early Treatment Diabetic Retinopathy Study (ETDRS) charts and measured as a logarithm of the minimum angle of resolution (LogMAR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Retinal Ganglion Cells Function at 9 Month | 9 months vs Baseline | Pattern-Electroretinogram recordings. Increase of P50-N95 amplitude (measured in microvolt) |
| Change From Baseline in Optic Nerve Function at 9 Months | 9 months vs baseline | Visual Evoked Potentials recordings. Shortening of the main parameter P100 Implicit time measured in milliseconds |
| Change From Baseline in Optic Nerve Morphology at 9 Months | 9 months vs baseline | Reduction of Overall Retinal Nerve Fiber Thickness by Optical Coherence Tomography measured in micron |
| Change From Baseline in Visual Field Defects at 9 Months | 9 months vs baseline | improvement of the visual field by static perimetry (increase of the main indexes Mean Deviation measured in dB). |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NAION Patients OS-Citicoline Treated In 20 patients with NAION, OS-Citicoline will be administered (500 mg/day) for 6 months followed by three months of suspension (NC Group) | 20 |
| NAION Patients OS-Citicoline Treated In 20 patients with NAION, OS-Citicoline will be administered (500 mg/day) for 6 months followed by three months of suspension (NC Group) | 20 |
| NAION Patients Untreated In 20 patients with NAION, no type of treatment will be performed during 9 months of observation (NN Group) | 20 |
| NAION Patients Untreated In 20 patients with NAION, no type of treatment will be performed during 9 months of observation (NN Group) | 20 |
| Total | 80 |
Baseline characteristics
| Characteristic | NAION Patients OS-Citicoline Treated | NAION Patients Untreated | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 8 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 12 Participants | 23 Participants |
| Number of Participants with NAION diagnosis in the last 6 - 12 months | 20 Participants | 20 Participants | 40 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 20 Participants | 40 Participants |
| Region of Enrollment Italy | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 12 Participants | 13 Participants | 25 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 17 |
| other Total, other adverse events | 0 / 19 | 0 / 17 |
| serious Total, serious adverse events | 0 / 19 | 0 / 17 |
Outcome results
Primary
Change From Baseline in Visual Acuity at 9 Month
Increase of Visual Acuity evaluated by Early Treatment Diabetic Retinopathy Study (ETDRS) charts and measured as a logarithm of the minimum angle of resolution (LogMAR)
Time frame: 9 months vs baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NAION Patients OS-Citicoline Treated | Change From Baseline in Visual Acuity at 9 Month | -0.0574 LogMAR | Standard Deviation 0.1147 |
| NAION Patients Untreated | Change From Baseline in Visual Acuity at 9 Month | 0.0535 LogMAR | Standard Deviation 0.0914 |
Secondary
Change From Baseline in Optic Nerve Function at 9 Months
Visual Evoked Potentials recordings. Shortening of the main parameter P100 Implicit time measured in milliseconds
Time frame: 9 months vs baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NAION Patients OS-Citicoline Treated | Change From Baseline in Optic Nerve Function at 9 Months | 127.05 milliseconds | Standard Deviation 8.35 |
| NAION Patients Untreated | Change From Baseline in Optic Nerve Function at 9 Months | 126.88 milliseconds | Standard Deviation 6.5 |
Secondary
Change From Baseline in Optic Nerve Morphology at 9 Months
Reduction of Overall Retinal Nerve Fiber Thickness by Optical Coherence Tomography measured in micron
Time frame: 9 months vs baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NAION Patients OS-Citicoline Treated | Change From Baseline in Optic Nerve Morphology at 9 Months | 57.71 micron | Standard Deviation 9.43 |
| NAION Patients Untreated | Change From Baseline in Optic Nerve Morphology at 9 Months | 63.99 micron | Standard Deviation 8.44 |
Secondary
Change From Baseline in Retinal Ganglion Cells Function at 9 Month
Pattern-Electroretinogram recordings. Increase of P50-N95 amplitude (measured in microvolt)
Time frame: 9 months vs Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NAION Patients OS-Citicoline Treated | Change From Baseline in Retinal Ganglion Cells Function at 9 Month | 1.32 microvolt | Standard Deviation 0.39 |
| NAION Patients Untreated | Change From Baseline in Retinal Ganglion Cells Function at 9 Month | 1.38 microvolt | Standard Deviation 0.28 |
Secondary
Change From Baseline in Visual Field Defects at 9 Months
improvement of the visual field by static perimetry (increase of the main indexes Mean Deviation measured in dB).
Time frame: 9 months vs baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NAION Patients OS-Citicoline Treated | Change From Baseline in Visual Field Defects at 9 Months | -15.61 dB | Standard Deviation 6.43 |
| NAION Patients Untreated | Change From Baseline in Visual Field Defects at 9 Months | -13.02 dB | Standard Deviation 7.15 |