To evaluate the efficacy of citicoline eye drops 2% in reducing visual field deterioration in patients with progressing OAG treated according to best clinical practice. Secondary objectives are assessing the effect of citicoline eye drops 2% on changes in structural parameters measured by Spectral Domain Optical Coherence Tomography (SD-OCT) and evaluating the safety of citicoline eye drops 2%
Background: Primary open angle glaucoma (OAG) is a chronic progressive neurodegenerative disease where intraocular pressure (IOP) is the main and successfully treatable risk factor. Although the treatment effect is quite large, a significant proportion of patients show disease progression with apparently well controlled IOP. Given the similarities with other neurodegenerative diseases - particularly in the mechanisms of cell death - neuroprotective treatments have been tested also in glaucoma. Interesting results from experimental studies and first evidence from human glaucoma trials have been published in recent years. Citicoline is one of the promising molecules with a putative neuroprotective action and has been evaluated in patients with various neurodegenerative diseases with encouraging results. The mechanism of action of citicoline is multifarious and includes preservation of cardiolipin and sphingomyelin, restoration of phosphatidylcholine, stimulation of glutathione synthesis, lowering of glutamate concentration, rescuing mitochondrial function, and others. Pilot studies on glaucomatous patients showed a possible effect of citicoline as additive therapy in the treatment of glaucoma, in reducing progression of visual field changes, in protecting retinal nerve fiber layers and in improving vision related Quality of Life (QoL), though these findings are yet to be confirmed by a large randomized clinical trial.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
1,000
Eye drops containing Citicoline 2%
Eye drops containing placebo matching product
Presidio Ospedale San Paolo
Milan, MI, Italy
RECRUITINGProgression of visual field damage
Difference in the rate of progression of VF damage in the study eye between the two trial arms. This will be measured with repeated, planned visual field (VF) tests, all performed with a Humphrey Field Analyser (HFA, Zeiss Meditec, Dublin, CA) with the SITA Standard 24-2 strategy, over the span of three years.
Time frame: 3 years
Rate of progression in structural parameters
Difference in the rate of progression in structural parameters. These parameters focus on the ocular structures mostly damaged by glaucoma. The parameters of interest will be: * RNFL thickness measured with Optical Coherence Tomography (OCT). * Inner retina thickness in the macula (RNFL, Ganglion Cell Layer and Ganglion Cell + Inner Plexiform Layer complex).
Time frame: 3 years
Safety (IOP)
Safety will be assured by regular assessments of adverse events and IOP. IOP will be carefully monitored and managed as per standard clinical practice (detailed management of IOP is reported later). Side effects from the neuroprotective drops or any IOP lowering treatment, including allergic reactions, ocular surface toxicity and signs of extraocular or intraocular inflammation, will be carefully assessed by the examiners and reported in the case report form (CRF). Any significant discomfort or adverse reactions to the drops or clear signs of inflammation will be reasons for early withdrawal
Time frame: 3 years
Visual Field recovery
Evidence of neuro-recovery. The Visual field Mean Deviation values (2 tests) at Visit 2 will be compared between the two groups, after adjusting for the MD values at Visit 1 (baseline, 2 tests).
Time frame: 3 years
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