Long-term Retinal Changes After Topical Citicoline Administration in Patients With Mild Signs of Diabetic Retinopathy in Type 1 Diabetes Mellitus.

Diabetic Retinopathy Clinical Trial

Official title:

Long-term Morphological and Functional Retinal Changes After Topical Citicoline Administration in Patients With Mild Signs of Diabetic Retinopathy in Type 1 Diabetes Mellitus: Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04009980
• Other study ID #: RET04/2015
• Status: Completed
• Phase: N/A
• Start date: September 23, 2015
• Est. completion date: June 7, 2019

Study information

• Verified date: July 2019
• Source: Fondazione G.B. Bietti, IRCCS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Citicoline (cytidine-5'-diphosphocholine) is an essential precursor in the synthesis of phosphatidylcholine, a component of cell membranes. Several experimental in vitro and in vivo studies have suggested that citicoline plays a neuroprotective role.

A recent clinical study has shown that treatment with topical citicoline induces, after 60 days of therapy, a significant improvement in the ganglion cell function .In addition topical citicoline has been demonstrated in vivo a neuroprotective effect in preventing diabetic retinopathy .

The Investigators want to evaluate if citicoline may reduce the progression of retinal damage in patients with mild diabetic retinopathy.

Description:

The investigators evaluated patients with mild signs of diabetic retinopathy (DR) treated with eye-drop solution with citicoline ( OMk2 ophthalmic solution).

All patients was randomized in two groups (10:10), one receiving topical administration of OMk2 ophthalmic solution for 36 months and one group receiving only the excipients of OMk2 (placebo).

Omk2 ophthalmic solution and the placebo will be used for 36 months three times/day.

They will undergo a complete ocular examination at baseline and at 6-, 12-, 18-, 24-, 30- and 36- months after treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 7, 2019
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Diagnosis of type 1 DM

• Diagnosis of mild Diabetic rethnopathy (DR)

• Retinal sensitivity impairment evaluated by means of frequency doubling technology (Matrix FDT) with a mean deviation (MD) p value <5% or with two locations with p <5% and one location with p<1% in the total or pattern deviation plots.

Exclusion Criteria:

• Hyperopia higher than +5 diopter (D)

• myopia higher than -8 D

• astigmatism higher than 2 D

• Visual acuity below 20/25

• significant media opacity

• previous ocular surgery

• previous diagnosis of glaucoma

• uveitis

• retinal disease other than mild diabetic retinopathy

• patients with any ocular disease

• systemic disease other than diabetes

• Any signs of diabetic retinopathy more advanced than mild as coded by ICDRSS (e.g. macular edema or any sign of proliferative DR)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetic Retinopathy
• Retinal Diseases

Intervention

Other:
• OMK2 group
topical administration of OMk2 ophthalmic solution for 36 months three times/day
• Placebo group
topical administration of ophthalmic placebo solution for 36 months three times/day

Locations

Country	Name	City	State
Italy	Fondazione G.B.Bietti	Roma

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione G.B. Bietti, IRCCS

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Diederich K, Frauenknecht K, Minnerup J, Schneider BK, Schmidt A, Altach E, Eggert V, Sommer CJ, Schäbitz WR. Citicoline enhances neuroregenerative processes after experimental stroke in rats. Stroke. 2012 Jul;43(7):1931-40. doi: 10.1161/STROKEAHA.112.654806. Epub 2012 May 10. Erratum in: Stroke. 2012 Nov;43(11):e169. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

van Dijk HW, Verbraak FD, Kok PH, Garvin MK, Sonka M, Lee K, Devries JH, Michels RP, van Velthoven ME, Schlingemann RO, Abràmoff MD. Decreased retinal ganglion cell layer thickness in patients with type 1 diabetes. Invest Ophthalmol Vis Sci. 2010 Jul;51(7):3660-5. doi: 10.1167/iovs.09-5041. Epub 2010 Feb 3. — View Citation

Vujosevic S, Midena E. Retinal layers changes in human preclinical and early clinical diabetic retinopathy support early retinal neuronal and Müller cells alterations. J Diabetes Res. 2013;2013:905058. doi: 10.1155/2013/905058. Epub 2013 Jun 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes of Retinal sensitivity and contrast sensitivity function after topical citicoline use in patients with diabetic retinopathy	To evaluate functional retinal parameters : retinal sensitivity by Humphrey Matrix and contrast sensitivity function by Pelli Robson in patients with diabetic retinopathy	Functional retinal changes at 36 months
Secondary	Morphological retinal changes after topical citicoline use in patients with diabetic retinopathy	To evaluate morphological retinal parameters by Spectral Domain OCT( SD-OCT ) and by Adaptive Optics (AO) at each time point of follow up : retinal thickness, RNFL thickness, inner retinal thickness and outer retinal thickness.	Morphological retinal changes at 36 months