Clinical trial NCT04009980: Long-term Retinal Changes After Topical Citicoline Administration in Patients With Mild Signs of Diabetic Retinopathy in Type 1 Diabetes Mellitus.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetic Retinopathy
Keywords: citicoline
neuropathy
Lead sponsor: Fondazione G.B. Bietti, IRCCS
Sponsor class: OTHER
First posted: 2019-07-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, interventional, randomized, double-masked, monocentric pilot study
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Changes of Retinal sensitivity and contrast sensitivity function after topical citicoline use in patients with diabetic retinopathy
timeFrame: Functional retinal changes at 36 months
Secondary outcomes:
measure: Morphological retinal changes after topical citicoline use in patients with diabetic retinopathy
timeFrame: Morphological retinal changes at 36 months
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Fondazione G.B.Bietti
Study officials:
References:
citation: van Dijk HW, Verbraak FD, Kok PH, Garvin MK, Sonka M, Lee K, Devries JH, Michels RP, van Velthoven ME, Schlingemann RO, Abramoff 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.
citation: Vujosevic S, Midena E. Retinal layers changes in human preclinical and early clinical diabetic retinopathy support early retinal neuronal and Muller cells alterations. J Diabetes Res. 2013;2013:905058. doi: 10.1155/2013/905058. Epub 2013 Jun 12.
citation: Diederich K, Frauenknecht K, Minnerup J, Schneider BK, Schmidt A, Altach E, Eggert V, Sommer CJ, Schabitz 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.
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.
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. doi: 10.1016/S0161-6420(99)90269-5.
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.
citation: Parravano M, Scarinci F, Parisi V, Giorno P, Giannini D, Oddone F, Varano M. Citicoline and Vitamin B12 Eye Drops in Type 1 Diabetes: Results of a 3-year Pilot Study Evaluating Morpho-Functional Retinal Changes. Adv Ther. 2020 Apr;37(4):1646-1663. doi: 10.1007/s12325-020-01284-3. Epub 2020 Mar 16.