Diabetic RetinopathyNCT04009980
Long-term Retinal Changes After Topical Citicoline Administration in Patients With Mild Signs of Diabetic Retinopathy in Type 1 Diabetes Mellitus.
A study testing OMK2 group in people with Diabetic Retinopathy, run by Fondazione G.B. Bietti, IRCCS at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Diabetic Retinopathy
- What is being tested?
- OMK2 group
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 23 Sep 2015to 7 Jun 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Diabetic Retinopathy
- Being tested
- OMK2 group, Placebo group
- Keywords
- citicoline, neuropathy
- Medical subject headings
- Diabetic Retinopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OMK2 groupOther
topical administration of OMk2 ophthalmic solution for 36 months three times/day
Placebo groupOther
topical administration of ophthalmic placebo solution for 36 months three times/day
| Study group | Role | What they receive |
|---|---|---|
| OMK2 group | Experimental | Patients receiving topical administration of OMk2 ophthalmic solution for 36 months three times/day Receives: Other: OMK2 group |
| Placebo group | Placebo comparator | Patients receiving receiving only the excipients of OMk2 (placebo) for 36 months three times/day Receives: Other: Placebo group |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Functional retinal changes at 36 months
Secondary outcomes (1)
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.
Measured: Morphological retinal changes at 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2019
- Study start23 Sep 2015
- Primary completionOct 2018
- Study completion7 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Diabetic RetinopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, interventional, randomized, double-masked, monocentric pilot study
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione G.B. Bietti, IRCCS
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mariacristina Parravano, Fondazione G.B. Bietti, IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04009980
- Sponsor's protocol ID
- RET04/2015
- Status last verified
- Jul 2019
- First submitted
- 6 Jun 2019
- Last updated
- 8 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 20130282Vujosevic 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.
PubMed 23841106Diederich 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.
PubMed 22581817Parisi 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.
PubMed 18929133Parisi 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.
PubMed 10366081Roberti 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.
PubMed 24881599Parravano 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.
PubMed 32180131
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04009980
- Acronym / sponsor ID
- RET04/2015
- Conditions
- Diabetic Retinopathy
- Keywords
- citicoline, neuropathy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Fondazione G.B. Bietti, IRCCSUniversity, hospital or other
- Study start
- 23 Sep 2015 (actual)
- Primary completion
- Oct 2018 (actual)
- Study completion
- 7 Jun 2019 (actual)
- First posted
- 8 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Prospective, interventional, randomized, double-masked, monocentric pilot study
| Arm | Type | Receives |
|---|---|---|
| OMK2 group | Experimental | Other: OMK2 groupPatients receiving topical administration of OMk2 ophthalmic solution for 36 months three times/day |
| Placebo group | Placebo comparator | Other: Placebo groupPatients receiving receiving only the excipients of OMk2 (placebo) for 36 months three times/day |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (12 listed)
- Hyperopia higher than +5 diopter (D)
- myopia higher than -8 D
- astigmatism higher than 2 D
- Visual acuity below 20/25
- significant media opacity
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OMK2 grouptopical administration of OMk2 ophthalmic solution for 36 months three times/day | Other | OMK2 group |
| Placebo grouptopical administration of ophthalmic placebo solution for 36 months three times/day | Other | Placebo group |
Primary outcome
Changes of Retinal sensitivity and contrast sensitivity function after topical citicoline use in patients with diabetic retinopathy
Time frame: Functional retinal changes at 36 months
To evaluate functional retinal parameters : retinal sensitivity by Humphrey Matrix and contrast sensitivity function by Pelli Robson in patients with diabetic retinopathy
1 secondary outcome
Morphological retinal changes after topical citicoline use in patients with diabetic retinopathy
Time frame: Morphological retinal changes at 36 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2019.
- Background: PubMed 20130282van 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.
- Background: PubMed 23841106Vujosevic 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.
- Background: PubMed 22581817Diederich 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.
- Background: PubMed 18929133Parisi 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.
- Background: PubMed 10366081Parisi 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.
- Background: PubMed 24881599Roberti 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.
- Derived from this study: PubMed 32180131Parravano 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing OMK2 group in people with Diabetic Retinopathy, run by Fondazione G.B. Bietti, IRCCS at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes of Retinal sensitivity and contrast sensitivity function after topical citicoline use in patients with diabetic retinopathy (time frame: Functional retinal changes at 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04009980, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2019.