Dataset Information

Topical citicoline and vitamin B12 versus placebo in the treatment of diabetes-related corneal nerve damage: a randomized double-blind controlled trial.

ABSTRACT:

Background

To evaluate the effects of topical citicoline and vitamin B12 (Cit-B12: OMK2, Omikron Italia srl, Italy) on corneal innervation of patients with diabetic neuropathy.

Methods

This prospective, randomized, double blind, placebo-controlled study included 30 patients randomised with a 2:1 ratio to Cit-B12 or placebo 3 times daily for 18 months. At baseline and at months 4, 8, 12, 18 patients underwent the Ocular Surface Disease Index questionnaire (OSDI), tear break-up time, evaluation of corneal and conjunctival staining, Schirmer I test, Cochet-Bonnet esthesiometry, and confocal biomicroscopy of corneal sub-basal plexus (SBP). Fiber lenght density (FLD) was calculated using NeuronJ and expressed in mm/mm2. Raw data and differences from baseline were analysed in the two groups.

Results

29/30 patients concluded the study. The two groups had similar FLD at baseline; it progressively improved up to month 18 in both groups (Cit-B12, p < 0.0001; controls, < 0.0001-0.03); improvement at month 18 vs baseline was higher in Cit-B12 than placebo (33% vs 15%, p = 0.04). A progressive amelioration of corneal sensitivity (baseline, 28 ± 18 mm; month 18, 52 ± 10 mm, p < 0.0001), conjunctival staining (P = 0.04) and OSDI questionnaire (P = 0.05) were shown on Cit-B12 group alone. Both treatments were well tolerated and adherence during the study was high.

Conclusions

Cit-B12 ameliorated both morphology and function of corneal nerves in patients with diabetes, thus suggesting a neuroregenerative effect.

Trial registration

Trial registration NCT03906513 , retrospectively registered on 08 April 2019.

SUBMITTER: Fogagnolo P

PROVIDER: S-EPMC7395393 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Topical citicoline and vitamin B12 versus placebo in the treatment of diabetes-related corneal nerve damage: a randomized double-blind controlled trial.

Fogagnolo Paolo P Melardi Ettore E Tranchina Laura L Rossetti Luca L

BMC ophthalmology 20200801 1

<h4>Background</h4>To evaluate the effects of topical citicoline and vitamin B12 (Cit-B12: OMK2, Omikron Italia srl, Italy) on corneal innervation of patients with diabetic neuropathy.<h4>Methods</h4>This prospective, randomized, double blind, placebo-controlled study included 30 patients randomised with a 2:1 ratio to Cit-B12 or placebo 3 times daily for 18 months. At baseline and at months 4, 8, 12, 18 patients underwent the Ocular Surface Disease Index questionnaire (OSDI), tear break-up time ...[more]

PMID: 32738875

Similar Datasets

Project description:AimTo investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 μg/day for one year in patients with diabetic neuropathy (DN).Patients and methodsIn this prospective, double-blind, placebo-controlled trial, 90 patients with type 2 diabetes on metformin for at least four years and both peripheral and autonomic DN were randomized to an active treatment group (n = 44) receiving B12 and a control group (n = 46) receiving a placebo. All patients had B12 levels less than 400 pmol/L. Subjects underwent measurements of sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and vibration perception threshold (VPT), and they performed cardiovascular autonomic reflex tests (CARTs: mean circular resultant (MCR), Valsalva test, postural index, and orthostatic hypotension). Sudomotor function was assessed with the SUDOSCAN that measures electrochemical skin conductance in hands and feet (ESCH and ESCF, respectively). We also used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, respectively) and questionnaires to evaluate quality of life (QoL) and level of pain (pain score).ResultsB12 levels increased from 232.0 ± 71.8 at baseline to 776.7 ± 242.3 pmol/L at follow-up, p < 0.0001, in the active group but not in the control group. VPT, MNSIQ, QoL, pain score, SNCV, SNAP, and ESCF significantly improved in the active group (p < 0.001, p = 0.002, p < 0.0001, p < 0.000, p < 0.0001, p < 0.0001, and p = 0.014, respectively), whereas CARTS and MNSIE improved but not significantly. MCR, MNSIQ, SNCV, SNAP, and pain score significantly deteriorated in the control group (p = 0.025, p = 0.017, p = 0.045, p < 0.0001, and p < 0.0001, respectively).ConclusionsThe treatment of patients with DN with 1 mg of oral methylcobalamin for twelve months increased plasma B12 levels and improved all neurophysiological parameters, sudomotor function, pain score, and QoL, but it did not improve CARTS and MNSIE.

Project description:BackgroundAlcohol use disorder is a major societal and individual burden that exacerbates health outcomes, decreases quality of life, and negatively affects U.S. healthcare spending. Although pharmacological treatments are available for alcohol use disorder, many of them are limited by small effect sizes and used infrequently. Citicoline is a widely available over-the-counter supplement with a favorable side effect profile. It acts through cholinergic pathways and phospholipid metabolism. The current report examines the effect of oral citicoline on alcohol use, craving, depressive symptoms, and cognitive outcomes in individuals with alcohol use disorder.MethodsA 12-week, randomized, double-blind, parallel-group, placebo-controlled, pilot study of citicoline (titrated to 2,000 mg/d) in 62 adults (age 18 to 75) with alcohol use disorder was conducted. Alcohol use, such as number of drinking days, amount used, and number of heavy drinking days, was assessed using the Timeline Followback method and liver enzymes, while alcohol craving was measured using the Penn Alcohol Craving Scale. A neurocognitive battery (e.g., Rey Auditory Verbal Learning Test) and depressive symptoms scale (e.g., Inventory of Depressive Symptomatology Self-Report) scores were also collected. Data were analyzed using a random regression analysis.ResultsThe primary outcome analysis was conducted in the intent-to-treat sample and consisted of 55 participants (78.2% men and 21.8% women, mean age of 46.47 ± 9.15 years). In the assessment period, the drinking days, on average, represented 77% of the assessed days. Significant between-group differences were not observed on alcohol use, craving, and cognitive or depressive symptom measures. Citicoline was well tolerated.ConclusionsThis proof-of-concept study observed that citicoline was well tolerated, but was not associated with a reduction in alcohol use or other outcomes, as compared to placebo. The favorable effects reported with citicoline for cocaine use, cognitive disorders, and other conditions do not appear to extend to alcohol use disorder.

Project description:ImportanceOne-third of singers and vocal professionals report experiencing a benefit from empirical vitamin B12 injections for improvement of mild singing-related symptoms (eg, reduced stamina, vocal fatigue, and effort). However, there is no objective evidence to support or refute these claims.ObjectiveTo assess the presence and magnitude of the effect of empirical vitamin B12 injection on the vocal performance of singers.Design, setting, and participantsA randomized, double-blind, placebo-controlled, crossover trial was conducted from November 7, 2017, to November 30, 2018, at an academic voice center among 20 active adult singers without dysphonia but with mild vocal symptoms. Individuals with known or suspected vitamin B12 deficiency or active or recent vitamin B12 treatment were excluded. Analysis was on a per-protocol basis.InterventionsParticipants were randomized to receive an intramuscular (deltoid) injection of either vitamin B12 (1000 μg of cyanocobalmin) or placebo (0.9% sodium chloride). After a washout period of at least 4 weeks, participants were crossed over to receive the opposite injection. Both the investigators and participants were blinded to the order of injections.Main outcomes and measuresThe participants completed the Singing Voice Handicap Index-10 (SVHI-10), the Voice Fatigue Index (VFI), and the Evaluation of the Ability to Sing Easily (EASE) before each injection and at intervals of 1 hour, 3 hours, 24 hours, 72 hours, and 1 week after the injection. The primary time point assessment was 72 hours after injection, and the SVHI-10 score was the primary outcome measure.ResultsTwenty singers (10 men; median age, 22 years [range, 19-42 years]) were enrolled. The improvements after either placebo or vitamin B12 injections were comparable to each other. At 72 hours after the vitamin B12 injection, the median difference in the SVHI-10 score was 1 (95% CI, -1 to 2) compared with 3 (95% CI, 0-4) after placebo. The median difference between differences at 72 hours between placebo and vitamin B12 injections were 1.5 (95% CI, -2 to 5) for the SVHI-10, 1 (95% CI, -9 to 9) for the VFI, and -1 (95% CI, -3 to 2) for the EASE. The improvements after both injections failed to reach the estimated minimal clinically important difference. Of the 20 participants, 4 (20%) reached the estimated minimal clinically important difference in their SVHI-10 score after 72 hours for both vitamin B12 and placebo injections.Conclusions and relevanceThis randomized, double-blind, placebo-controlled, crossover trial found that after empirical vitamin B12 injection to improve mild voice-related symptoms, the improvement in self-reported voice measures in singers shows no meaningful difference compared with placebo.Trial registrationClinicalTrials.gov Identifier: NCT03437824.

Project description:BackgroundSupplementation of citicoline (CDP-choline), a naturally occurring mononucleotide, has shown beneficial effects on memory function and behavior in populations with a wide range of impairments. However, few studies have investigated its effect in healthy older populations.ObjectiveThe objective of this study was to investigate the effects of citicoline (Cognizin®), on memory in healthy elderly populations with age-associated memory impairment (AAMI).MethodsA total of 100 healthy men and women aged between 50 and 85 y with AAMI participated in this randomized, double-blind, placebo-controlled trial. Participants were randomized to receive placebo (n = 51) or citicoline (n = 49; 500 mg/d) for 12 wk. Memory function was assessed at baseline and end of the intervention (12 wk) using computerized tests (Cambridge Brain Sciences, Ontario, Canada). Safety measurements included adverse events query, body weight, blood pressure, and hematology and metabolic panel. Intent-to-treat analysis was conducted using ANCOVA for the primary and secondary outcome variables with Bonferroni correction for multiple comparisons.ResultsA total of 99 out of 100 participants completed the study in its entirety. After the 12-wk intervention, participants supplemented with citicoline showed significantly greater improvements in secondary outcomes of episodic memory (assessed by the Paired Associate test), compared with those on placebo (mean: 0.15 vs. 0.06, respectively, P = 0.0025). Composite memory (secondary outcome), calculated using the scores of 4 memory tests, also significantly improved to a greater extent following citicoline supplementation (mean: 3.78) compared with placebo (mean: 0.72, P = 0.0052).ConclusionsDietary supplementation of citicoline for 12 wk improved overall memory performance, especially episodic memory, in healthy older males and females with AAMI. The findings suggest that regular consumption of citicoline may be safe and potentially beneficial against memory loss due to aging. This trial was registered at clinicaltrials.gov as NCT03369925.

Project description:PURPOSE:To evaluate the presence and concentration of citicoline and its metabolites (choline, cytidine and uridine) in the vitreous body in human eyes after topical application of an ophthalmic solution of citicoline 2%, in vivo. METHODS:Twenty-one subjects affected by epiretinal membrane with surgical indication for pars-plana vitrectomy underwent treatment with 1 drop 3 times/day of a solution of citicoline 2%, 0.2% high molecular weight hyaluronic acid and 0.01% benzalkonium chloride (OMK1, Omikron Italia s.r.l., Rome, Italy) 14 days before surgery and 2 hours prior to surgery. Five additional patients served as controls and received an OMK1 vehicle solution without citicoline. The vitreous samples were taken at the beginning of the pars-plana vitrectomy and analyzed for qualitative/quantitative determination of vitreous concentration of citicoline and its metabolites by means of high performance liquid chromatography. RESULTS:The overall mean concentration of citicoline in patients treated with citicoline 2% solution was 406.72 ± 52.99 μg/mL, while the mean concentration of choline, cytidine and uridine was 180.88 ± 41.49 μg/mL, 44.45 ± 10.19 μg/mL and 330.41 ± 75.8 μg/mL, respectively. The concentration of citicoline in phakic eyes (n = 13, 366.61 ± 129.61 μg/mL) was lower compared to that found in pseudophakic eyes (n = 8, 435.89 ± 131.42 μg/mL) and the difference was not statistically significant. The concentration of citicoline in the control eyes was 45.66 ± 26.36 μg/mL, while the concentration of choline, cytidine and uridine were 17.21 ± 9.93 μg/mL, 6.24 ± 3.6 μg/mL and 172.80 ± 99.76 μg/mL, respectively. CONCLUSION:Citicoline can reach the human vitreous in high concentration when administered in ophthalmic solution. This evidence contributes to the build-up of the pyramid of the evidences required for determining the role of citicoline administered in ophthalmic formulation in retinal and optic nerve neurodegenerative diseases.

Dataset Information

Topical citicoline and vitamin B12 versus placebo in the treatment of diabetes-related corneal nerve damage: a randomized double-blind controlled trial.

Background

Methods

Results

Conclusions

Trial registration

Publications

Topical citicoline and vitamin B12 versus placebo in the treatment of diabetes-related corneal nerve damage: a randomized double-blind controlled trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets