Multimodal Morpho-functional Study in Glaucoma Patients-Citicoline Oral Solution

NCT05315206 | Active Not Recruiting

• 1 other identifier: 128/21/FB
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

A prospective, multicentre, randomized, blinded, masked study that involves the enrollment of 60 patients affected by open angle glaucoma (OAG). Patients selected according to the inclusion / exclusion criteria, after signing the informed consent, will be randomized into two groups:

1. 1.In a group of patients with OAG, Citicoline in oral solution (10 ml / day, Neurotidine®) will be administered for 12 months (Citicoline Treated Group, TC Group)
2. 2.in another group of patients with OAG will be administered Placebo (Containing all excipients of Neurotidine ®) (10 ml / day) for 12 months (Placebo Treated Group, TP Group) Randomization will be done by dividing the selected patients into two groups based on similar characteristics of: age, perimetric defect and, mainly, retinal-cortical time (RCT) values.

Conditions

Primary Open Angle Glaucoma

Outcome Measures

Primary Outcomes (1)

• Retino-cortical time (RCT) changes after treatment with citicoline in oral solution.

  The changes of the retino-cortical time (RCT) in patients affected by open angle glaucoma after one years of treatment with Citicoline in oral solution compared to patients affected by open angle glaucoma treated with placebo.

  One year

Secondary Outcomes (1)

• Correlation between RCT changes and morpho-functional parameters changes after treatment with citicoline in oral solution.

  one year

Study Arms (2)

Citicoline Treated Group, TC Group

EXPERIMENTAL

In a group of patients with open angle glaucoma (OAG), Citicoline in oral solution (10 ml / day) will be administered for 12 months (Citicoline Treated Group, TC Group)

Dietary Supplement: Citicoline

Placebo Treated Group, TP Group

PLACEBO COMPARATOR

in another group of patients with open angle glaucoma (OAG) will be administered Placebo (Containing all excipients of Citicoline in oral solution) (10 ml / day) for 12 months (Placebo Treated Group, TP Group)

Dietary Supplement: Placebo

Interventions

Citicoline DIETARY_SUPPLEMENT

The patient will be given 10 ml of Citicoline oral solution (Neurotidine ®) once a day in the morning for 1 year. To patients will be given 4 bottles containing 500 ml of Citicoline and the relative instructions for administration. After 6 months, the patient will bring back the used bottles and will be given additional 4 bottles containing Citicoline (Neurotidine ®). Again at the end of this 6 month period the patient will bring back the used bottles. Each bottle of Neurotidine will contain: water; fructose; Citicoline (500 mg per 10 ml); acidity regulators: sodium citrate, sodium hydroxide; preservative: potassium sorbate; dye: riboflavine.

Citicoline Treated Group, TC Group

Placebo DIETARY_SUPPLEMENT

The patient will be given 10 ml of an oral solution of Placebo. Each bottle of Placebo, the solution of which will be indistinguishable from the active product in terms of appearance and flavor, will contain: water; fructose; acidity regulators: sodium citrate, sodium hydroxide; preservative: potassium sorbate; dye: riboflavin

Placebo Treated Group, TP Group

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 20 and 70 years old
• Diagnosis of glaucoma. Glaucoma is defined as: glaucomatous damage of the CV (Humphrey 24-2 standard SITA with mean deviation between -6 and -25 dB) and glaucomatous appearance of the optic nerve
• Visual acuity not less than 5/10
• Eye pressure below 21 mmHg with the use of ocular hypotonizing drugs including sympathomimetics, beta-blockers, prostaglandins, beta-adrenergics, carbonic anhydrase inhibitors. Such drugs can be used both alone and in combination with each other.
• Documented post-retinal nerve conduction delay through simultaneous recording of VEP and PERG showing an increase in RCT

You may not qualify if:

• Ocular surgery in the 3 months preceding the study, including surgery for cataracts in the previous three months.
• Cataract or maculopathy
• Argon laser trabeculoplasty (ALT) within the previous 6 months
• Known hypersensitivity to the study product
• Secondary causes of ocular hypertension, including systemic or topical use of steroids
• Positive history of ocular or systemic diseases that could preclude enrollment in the study in the opinion of the investigators
• Changes in systemic therapies that could compromise intraocular pressure values (beta-blockers, alpha and beta adrenergics, calcium inhibitors, ACE inhibitors) in the 30 days prior to enrollment
• Pregnancy, breastfeeding
• Diabetes
• Systemic lupus erythematosus, rheumatoid arthritis, connectivitis
• Concomitant use of anticoagulants and lithium

Sponsors & Collaborators

• Fondazione G.B. Bietti, IRCCS: lead

Study Sites (2)

Fondazione BIetti, Britannico Hospital

Roma, 00184, Italy

Location

Fondazione G.B. Bietti-IRCCS

Rome, 00199, Italy

Location

Related Publications (22)

• Quigley HA, McKinnon SJ, Zack DJ, Pease ME, Kerrigan-Baumrind LA, Kerrigan DF, Mitchell RS. Retrograde axonal transport of BDNF in retinal ganglion cells is blocked by acute IOP elevation in rats. Invest Ophthalmol Vis Sci. 2000 Oct;41(11):3460-6.

  PMID: 11006239 RESULT

• Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med. 1994 Mar 3;330(9):613-22. doi: 10.1056/NEJM199403033300907. No abstract available.

  PMID: 7905600 RESULT

• Oddone F, Lucenteforte E, Michelessi M, Rizzo S, Donati S, Parravano M, Virgili G. Macular versus Retinal Nerve Fiber Layer Parameters for Diagnosing Manifest Glaucoma: A Systematic Review of Diagnostic Accuracy Studies. Ophthalmology. 2016 May;123(5):939-49. doi: 10.1016/j.ophtha.2015.12.041. Epub 2016 Feb 15.

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• Parisi V. Impaired visual function in glaucoma. Clin Neurophysiol. 2001 Feb;112(2):351-8. doi: 10.1016/s1388-2457(00)00525-3.

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• Burgoyne CF, Downs JC, Bellezza AJ, Suh JK, Hart RT. The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage. Prog Retin Eye Res. 2005 Jan;24(1):39-73. doi: 10.1016/j.preteyeres.2004.06.001.

  PMID: 15555526 RESULT

• Furlanetto RL, Teixeira SH, Gracitelli CPB, Lottenberg CL, Emori F, Michelan M, Amaro E Jr, Paranhos A Jr. Structural and functional analyses of the optic nerve and lateral geniculate nucleus in glaucoma. PLoS One. 2018 Mar 23;13(3):e0194038. doi: 10.1371/journal.pone.0194038. eCollection 2018.

  PMID: 29570721 RESULT

• Schmidt MA, Knott M, Heidemann R, Michelson G, Kober T, Dorfler A, Engelhorn T. Investigation of lateral geniculate nucleus volume and diffusion tensor imaging in patients with normal tension glaucoma using 7 tesla magnetic resonance imaging. PLoS One. 2018 Jun 7;13(6):e0198830. doi: 10.1371/journal.pone.0198830. eCollection 2018.

  PMID: 29879191 RESULT

• Aksoy DO, Umurhan Akkan JC, Alkan A, Aralasmak A, Otcu Temur H, Yurtsever I. Magnetic Resonance Spectroscopy Features of the Visual Pathways in Patients with Glaucoma. Clin Neuroradiol. 2019 Dec;29(4):615-621. doi: 10.1007/s00062-018-0728-7. Epub 2018 Oct 5.

  PMID: 30291364 RESULT

• Wang Y, Wang X, Zhou J, Qiu J, Yan T, Xie Y, Li L, Lu W. Brain morphological alterations of cerebral cortex and subcortical nuclei in high-tension glaucoma brain and its associations with intraocular pressure. Neuroradiology. 2020 Apr;62(4):495-502. doi: 10.1007/s00234-019-02347-1. Epub 2019 Dec 23.

  PMID: 31872278 RESULT

• Gracitelli CPB, Duque-Chica GL, Sanches LG, Moura AL, Nagy BV, Teixeira SH, Amaro E Jr, Ventura DF, Paranhos A Jr. Structural Analysis of Glaucoma Brain and its Association With Ocular Parameters. J Glaucoma. 2020 May;29(5):393-400. doi: 10.1097/IJG.0000000000001470.

  PMID: 32079996 RESULT

• Parisi V, Manni G, Colacino G, Bucci MG. Cytidine-5'-diphosphocholine (citicoline) improves retinal and cortical responses in patients with glaucoma. Ophthalmology. 1999 Jun;106(6):1126-34. doi: 10.1016/S0161-6420(99)90269-5.

  PMID: 10366081 RESULT

• Parisi V, Centofanti M, Ziccardi L, Tanga L, Michelessi M, Roberti G, Manni G. Treatment with citicoline eye drops enhances retinal function and neural conduction along the visual pathways in open angle glaucoma. Graefes Arch Clin Exp Ophthalmol. 2015 Aug;253(8):1327-40. doi: 10.1007/s00417-015-3044-9. Epub 2015 May 26.

  PMID: 26004075 RESULT

• 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.

  PMID: 16249960 RESULT

• Parisi V, Coppola G, Centofanti M, Oddone F, Angrisani AM, Ziccardi L, Ricci B, Quaranta L, Manni G. Evidence of the neuroprotective role of citicoline in glaucoma patients. Prog Brain Res. 2008;173:541-54. doi: 10.1016/S0079-6123(08)01137-0.

  PMID: 18929133 RESULT

• 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.

  PMID: 31348806 RESULT

• Parisi V, Oddone F, Ziccardi L, Roberti G, Coppola G, Manni G. Citicoline and Retinal Ganglion Cells: Effects on Morphology and Function. Curr Neuropharmacol. 2018;16(7):919-932. doi: 10.2174/1570159X15666170703111729.

  PMID: 28676014 RESULT

• Oddone F, Rossetti L, Parravano M, Sbardella D, Coletta M, Ziccardi L, Roberti G, Carnevale C, Romano D, Manni G, Parisi V. Citicoline in Ophthalmological Neurodegenerative Disease: A Comprehensive Review. Pharmaceuticals (Basel). 2021 Mar 20;14(3):281. doi: 10.3390/ph14030281.

  PMID: 33804675 RESULT

• Rejdak R, Toczolowski J, Kurkowski J, Kaminski ML, Rejdak K, Stelmasiak Z, Grieb P. Oral citicoline treatment improves visual pathway function in glaucoma. Med Sci Monit. 2003 Mar;9(3):PI24-8.

  PMID: 12640353 RESULT

• Virno M, Pecori-Giraldi J, Liguori A, De Gregorio F. The protective effect of citicoline on the progression of the perimetric defects in glaucomatous patients (perimetric study with a 10-year follow-up). Acta Ophthalmol Scand Suppl. 2000;(232):56-7. doi: 10.1111/j.1600-0420.2000.tb01107.x. No abstract available.

  PMID: 11235540 RESULT

• Roberti G, Tanga L, Parisi V, Sampalmieri M, Centofanti M, Manni G. A preliminary study of the neuroprotective role of citicoline eye drops in glaucomatous optic neuropathy. Indian J Ophthalmol. 2014 May;62(5):549-53. doi: 10.4103/0301-4738.133484.

  PMID: 24881599 RESULT

• 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.

  PMID: 18557920 RESULT

• Parisi V, Miglior S, Manni G, Centofanti M, Bucci MG. Clinical ability of pattern electroretinograms and visual evoked potentials in detecting visual dysfunction in ocular hypertension and glaucoma. Ophthalmology. 2006 Feb;113(2):216-28. doi: 10.1016/j.ophtha.2005.10.044. Epub 2006 Jan 10.

  PMID: 16406535 RESULT

MeSH Terms

Conditions

Glaucoma, Open-Angle

Interventions

Cytidine Diphosphate Choline

Condition Hierarchy (Ancestors)

Glaucoma; Ocular Hypertension; Eye Diseases

Intervention Hierarchy (Ancestors)

Choline; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Cytidine Diphosphate; Cytosine Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Officials

• Vincenzo VP Parisi, MD

  IRCSS Fondazione Bietti

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Only after the signing of the informed consent, a single investigator ("enrolling physician"), not involved in the clinical and instrumental evaluations, will decide whether to assign the selected patient to one of two groups: treated-Citicoline or treated-Placebo. Randomization will be done by dividing the selected patients into two groups based on similar characteristics of: age, perimetric defect and, mainly,retinal cortical time (RCT) values.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Neurophysiology and Neurophthalmology Research Unit

Model Details: Patients selected according to the inclusion / exclusion criteria, after signing the informed consent, will be randomized into two groups: 1. In a group of patients with open angle glaucoma (OAG), Citicoline in oral solution (10 ml / day, Neurotidine®) will be administered for 12 months (Citicoline Treated Group, TC Group) 2. in another group of patients with OAG will be administered Placebo (Containing all excipients of Neurotidine ®) (10 ml / day) for 12 months (Placebo Treated Group, TP Group)

Study Record Dates

• First Submitted: February 4, 2022
• First Posted: April 7, 2022
• Study Start: January 25, 2022
• Primary Completion: December 31, 2023
• Study Completion: July 1, 2025
• Last Updated: February 26, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: As soon as possible when the study will be completed. About 6 months after the end of the data collection
• Access Criteria: The results of this study will be avaiable after end of the study ( 18-24 months) and their publication on a scientific journal.

Locations

IT (2)