Neural Conduction Along the Visual Pathways After Oral Treatment With Citicoline in Patients With Optic Nerve Diseases

Phase 4 Study of Evaluation of Neural Conduction Along the Visual Pathways Before and After Oral Treatment With Citicoline in Patients With Optic Nerve Diseases

In the management of glaucoma, as for as in other optic nerve diseases, an important goal of ophthalmologists is represented by the possibility of influencing visual function.

In this regard, Parisi et al [Ophthalmology 1999; 106:1126-1134.] suggested the intramuscular treatment with Cytidine-5-diphosphocholine (CDP-Choline or citicoline) to improve glaucomatous visual defects. In particular, recent studies reported the effects of citicoline on glaucomatous retinal and postretinal visual structures evaluated by electrophysiological examinations (PERG and VEP). It was observed that a 2-month period of treatment with citicoline may induce improvement in both ganglion cell function (PERGs with increase in amplitudes and shortening in times-to-peak) and in neural conduction along postretinal visual pathways (VEPs with increase in amplitudes and shortening in times-to-peak). The effects of citicoline on glaucomatous retinal and postretinal structures were not present 8 months after the end of treatment. However, performing several 2-month period of treatment with citicoline during a total period of 8 years, it was found a additional improvement of the glaucomatous retinal and postretinal impairment [Parisi V. Doc Ophthalmol. 2005 Jan;110:91-102). In this work, the investigators aimed to assess whether there similar visual function outcomes can be reached by the oral treatment with citicoline in patients affected by glaucomatous optic nerve disease as of as in other optic nerve diseases (i.e. non-arteritic ischemic optic neuropathy)

Study Overview

• Status: Completed
• Conditions: Glaucoma; Optic Neuropathy, Ischemic; Optic Nerve; Visual Pathway Disorder; Neural Conduction
• Intervention / Treatment: Drug: Citicoline

Detailed Description

Participants: 30 patients with open-angle glaucoma (OAG) and 15 patients (mean age 64.6±3.3ys) with non-arteritic ischemic optic neuropathy (NION) were enrolled enrolled.

Ten OAG patients will be untreated (NT-AOG, 10 eyes), while 20 OAG patients (T-AOG, 20 eyes) and 15 NION patients (T-NION, 14 eyes) were treated with Citicoline (oral treatment:1600 mg/die per 60 days) (Cebrolux®, Tubilux, Italy).

Methods: In T-OAG, NT-OAG and T-NION patients, Visual Evoked Potentials (VEPs)were recorded in response to 15' checkerboard pattern stimuli.

VEPs were assessed 5 times during a total period of 360 days: at baseline conditions (0 day), after two different cycles of 60 days of treatment (days 0-60 and days 180-240), and after two different cycles of 120 days of wash out (days 60-180 and 240-360). In NT-AOG patients, VEPs were assessed at baseline conditions (0 day) and after 60, 180, 240 and 360 days.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00199
    • Fondazione G.B. Bietti- IRCCS
  • Rome, Italy, 00199
    • Fondazione G.B. Bietti-IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Glaucoma Patients:

• IOP > 23 mmHg and < 28 mmHg (average of the two highest readings of the daily curve, from 8:00 a.m. to 6:00 p.m., six independent readings, one every two hours) without medical treatment;
• HFA with MD < - 2 dB; CPSD > +2 dB; fixation losses, false positive rate and false negative rate each less than 20%;
• best corrected visual acuity of 20/20 or better;
• one or more papillary signs on conventional color stereo-slides: the presence of a localized loss of neuroretinal rim (notch), thinning of the neuroretinal rim, generalized loss of optic rim tissue, optic disc excavation, vertical or horizontal cup/disc ratio greater than 0.5, cup-disc asymmetry between the two eyes greater than 0.2, peripapillary splinter hemorrhages;
• refractive error (when present) between -1.00 and +1.00 spherical equivalent;
• no previous history or presence of any disease involving cornea, lens, macula or retina;
• no previous history or presence of diabetes, optic neuritis, any disease involving the visual pathways;
• pupil diameter > 3 mm without mydriatic or miotic drugs.

Patients with non-arteritic ischemic optic neuropathy:

• IOP < 21 mmHg HFA with MD < - 2 dB; CPSD > +2 dB; fixation losses, false positive rate and false negative rate each less than 20%;
• refractive error (when present) between -1.00 and +1.00 spherical equivalent;
• no previous history or presence of any disease involving cornea, lens, macula or retina;
• no previous history or presence of diabetes of any further disease involving the visual pathways;
• pupil diameter > 3 mm without mydriatic or miotic drugs.

Exclusion Criteria:

All other condition that may influence Visual Evoked Potentials:

- previous history or presence of any disease involving cornea, lens, macula or retina or optic nerve (i.e inflammatory diseases)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Citicoline treatment; Ten OAG patients will be untreated (NT-AOG, 10 eyes), while 20 OAG patients (T-AOG, 20 eyes) and 15 NION patients (T-NION, 14 eyes) were treated with Citicoline (oral treatment:1600 mg/die per 60 days)	Drug: Citicoline; Ten OAG patients will be untreated (NT-AOG, 10 eyes), while 20 OAG patients (T-AOG, 20 eyes) and 15 NION patients (T-NION, 14 eyes) were treated with Citicoline (oral treatment:1600 mg/die per 60 days)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VEPs responses	P100 Implicit time and N75-P100 Amplitude	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Field Defects	Humphrey 24/1: Mean Deviation and Corrected Pattern Standard Deviation	24 months

Collaborators and Investigators

• Sponsor: Fondazione G.B. Bietti, IRCCS
• Investigators: Study Director: Vincenzo Parisi, MD, Fondazione G.B. Bietti-IRCCS, Rome, Italy

Publications and helpful links

General Publications

• Parisi V. Electrophysiological assessment of glaucomatous visual dysfunction during treatment with cytidine-5'-diphosphocholine (citicoline): a study of 8 years of follow-up. Doc Ophthalmol. 2005 Jan;110(1):91-102. doi: 10.1007/s10633-005-7348-7.

Helpful Links

• Fondazione G.B. Bietti-IRCCS activity (in italian language)

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2005
• Primary Completion (Actual): February 28, 2006
• Study Completion (Actual): July 30, 2006

Study Registration Dates

• First Submitted: November 28, 2006
• First Submitted That Met QC Criteria: November 28, 2006
• First Posted (Estimate): November 29, 2006

Study Record Updates

• Last Update Posted (Actual): February 3, 2021
• Last Update Submitted That Met QC Criteria: February 1, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Glaucoma; Optic nerve; Optic Neuropathy, Ischemic; Visual Pathways,; Neural conduction
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Eye Diseases; Ocular Hypertension; Cranial Nerve Diseases; Glaucoma; Optic Nerve Diseases; Optic Neuropathy, Ischemic; Nootropic Agents; Cytidine Diphosphate Choline
• Other Study ID Numbers: 86216880; 85356727 (FGBBIETTI)