Clinical trial NCT03758118: Citicoline in Non-Arteritic Ischemic Optic Neuropathy
Official title: Neuroprotection and Neuroenhancement in a Model of Optic Nerve Neurodegeneration (Non Arteritic Ischemic Optic Neuropathy): Study of Morpho-functional Changes Related to Treatment With Citicoline Oral Solution
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-arteritic Ischemic Optic Neuropathy
Keywords: Citicoline
Non-arteritic ischemic optic neuropathy
Neuroprotection
Neuroenhancement
Lead sponsor: Fondazione G.B. Bietti, IRCCS
Sponsor class: OTHER
First posted: 2018-11-29
Enrollment: 40
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Visual Acuity at 9 Month
timeFrame: 9 months vs baseline
Secondary outcomes:
measure: Change From Baseline in Retinal Ganglion Cells Function at 9 Month
timeFrame: 9 months vs Baseline
measure: Change From Baseline in Optic Nerve Function at 9 Months
timeFrame: 9 months vs baseline
measure: Change From Baseline in Optic Nerve Morphology at 9 Months
timeFrame: 9 months vs baseline
measure: Change From Baseline in Visual Field Defects at 9 Months
timeFrame: 9 months vs baseline
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Britannico Hospital
Study officials:
affiliation: Fondazione Bietti- IRCCS
name: Vincenzo MF Parisi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Carelli V, La Morgia C, Ross-Cisneros FN, Sadun AA. Optic neuropathies: the tip of the neurodegeneration iceberg. Hum Mol Genet. 2017 Oct 1;26(R2):R139-R150. doi: 10.1093/hmg/ddx273.
citation: Cho YS. The role of necroptosis in the treatment of diseases. BMB Rep. 2018 May;51(5):219-224. doi: 10.5483/bmbrep.2018.51.5.074.
citation: Hayreh SS, Zimmerman B. Visual field abnormalities in nonarteritic anterior ischemic optic neuropathy: their pattern and prevalence at initial examination. Arch Ophthalmol. 2005 Nov;123(11):1554-62. doi: 10.1001/archopht.123.11.1554.
citation: Patel HR, Margo CE. Pathology of Ischemic Optic Neuropathy. Arch Pathol Lab Med. 2017 Jan;141(1):162-166. doi: 10.5858/arpa.2016-0027-RS.
citation: Parisi V, Gallinaro G, Ziccardi L, Coppola G. Electrophysiological assessment of visual function in patients with non-arteritic ischaemic optic neuropathy. Eur J Neurol. 2008 Aug;15(8):839-45. doi: 10.1111/j.1468-1331.2008.02200.x. Epub 2008 Jun 28.
citation: Balducci N, Morara M, Veronese C, Barboni P, Casadei NL, Savini G, Parisi V, Sadun AA, Ciardella A. Optical coherence tomography angiography in acute arteritic and non-arteritic anterior ischemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol. 2017 Nov;255(11):2255-2261. doi: 10.1007/s00417-017-3774-y. Epub 2017 Aug 31.
citation: Khalilpour S, Latifi S, Behnammanesh G, Majid AMSA, Majid ASA, Tamayol A. Ischemic optic neuropathy as a model of neurodegenerative disorder: A review of pathogenic mechanism of axonal degeneration and the role of neuroprotection. J Neurol Sci. 2017 Apr 15;375:430-441. doi: 10.1016/j.jns.2016.12.044. Epub 2016 Dec 26.
citation: Parisi V, Barbano L, Di Renzo A, Coppola G, Ziccardi L. Neuroenhancement and neuroprotection by oral solution citicoline in non-arteritic ischemic optic neuropathy as a model of neurodegeneration: A randomized pilot study. PLoS One. 2019 Jul 26;14(7):e0220435. doi: 10.1371/journal.pone.0220435. eCollection 2019.