Layout table for study information Study Type : Interventional (Clinical Trial) ActualEnrollment : 155 participants Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment Official Title: Effect of Neurotidine (Citicoline Free Acid in Oral Solution) on Quality of Life in Patients With Glaucoma Actual Study Start Date : February 13, 2019 Actual Primary Completion Date : December 7, 2021 Actual Study Completion Date : January 24, 2022 Resource links provided by the National Library of Medicine MedlinePlus Genetics related topics: Early-onset glaucoma Hypertension MedlinePlus related topics: Glaucoma U.S. FDA Resources Arms and Interventions Go to Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Arm Intervention/treatment Experimental: Study Treatment500 ml oral solution containing citicoline free acid 50 mg/ml. Other: Food for special medical purposes: NeurotidineEach patient will be given the bottles for the first 3-month treatment period by the hospital pharmacist and will be asked to return them at the end of the period (3 months). Then the patients will be given the other bottles for the next phase of the study (3 months): these will contain placebo if the patient received Neurotidine in the first phase of the study and vice versa. Again, the patients will be asked to return after 3 months with the study bottles and will be given the last set of bottles for the final phase of the study (3 months).
Citicoline Drug Study Pdf Free
L-α-glycerylphosphorylcholine (α-GPC) is a recently developed cognitive enhancer whose mode of action is considered to involve the release of free choline, which is then utilized for acetylcholine and phosphatidylcholine biosynthesis in the brain. The purpose of this study was to evaluate the profile of free plasma choline levels following a single i.m. dose of α-GPC in 12 normal volunteers. Citicoline (CTC), which also acts as a choline precursor, was included for comparison purposes. Each subject was studied on three randomized occasions, (i) in a control day in the absence of drug administration (to evaluate the plasma level profile of endogenous choline), (ii) after i.m. α-GPC (1,000 mg) and (iii) after i.m. CTC (1,000 mg) respectively, with a wash-out period of at least 1-week between sessions. Blood samples for plasma choline HPLC determinations were collected at regular intervals over a 6 h period. In the control session, plasma choline levels remained stable during the sampling period. The administration of α-GPC was associated with a rapid rise in plasma choline, peak levels being usually observed at the first (0.25 h) or second (0.5 h) sampling time after the injection. Thereafter, the concentration of choline declined gradually and returned to near baseline values at the end of the observation period. After the administration of CTC, plasma choline levels showed a similar time course but were considerably lower than those observed after the administration of α-GPC. Pharmacokinetic parameters calculated after subtracting the zero time concentration from all post-drug values indicated that exogenously derived choline declined in plasma with a half-life of 0.5 to 6.2 h, without any significant difference between α-GPC or CTC. Choline AUC values after α-GPC were significantly higher than those observed after CTC, but the difference was no longer significant when AUCs were corrected for the different choline content of the two preparations (405 mg for α-GPC vs 213 mg for CTC). It is concluded that the i.m. administration of α-GPC provides an effective means of increasing plasma choline levels.
A comparative study of free plasma choline levels following intramuscular administration of L-α-glycerylphosphorylcholine and citicoline in normal volunteers. / Gatti, G.; Barzaghi, N.; Acuto, G. et al.
N2 - L-α-glycerylphosphorylcholine (α-GPC) is a recently developed cognitive enhancer whose mode of action is considered to involve the release of free choline, which is then utilized for acetylcholine and phosphatidylcholine biosynthesis in the brain. The purpose of this study was to evaluate the profile of free plasma choline levels following a single i.m. dose of α-GPC in 12 normal volunteers. Citicoline (CTC), which also acts as a choline precursor, was included for comparison purposes. Each subject was studied on three randomized occasions, (i) in a control day in the absence of drug administration (to evaluate the plasma level profile of endogenous choline), (ii) after i.m. α-GPC (1,000 mg) and (iii) after i.m. CTC (1,000 mg) respectively, with a wash-out period of at least 1-week between sessions. Blood samples for plasma choline HPLC determinations were collected at regular intervals over a 6 h period. In the control session, plasma choline levels remained stable during the sampling period. The administration of α-GPC was associated with a rapid rise in plasma choline, peak levels being usually observed at the first (0.25 h) or second (0.5 h) sampling time after the injection. Thereafter, the concentration of choline declined gradually and returned to near baseline values at the end of the observation period. After the administration of CTC, plasma choline levels showed a similar time course but were considerably lower than those observed after the administration of α-GPC. Pharmacokinetic parameters calculated after subtracting the zero time concentration from all post-drug values indicated that exogenously derived choline declined in plasma with a half-life of 0.5 to 6.2 h, without any significant difference between α-GPC or CTC. Choline AUC values after α-GPC were significantly higher than those observed after CTC, but the difference was no longer significant when AUCs were corrected for the different choline content of the two preparations (405 mg for α-GPC vs 213 mg for CTC). It is concluded that the i.m. administration of α-GPC provides an effective means of increasing plasma choline levels.
AB - L-α-glycerylphosphorylcholine (α-GPC) is a recently developed cognitive enhancer whose mode of action is considered to involve the release of free choline, which is then utilized for acetylcholine and phosphatidylcholine biosynthesis in the brain. The purpose of this study was to evaluate the profile of free plasma choline levels following a single i.m. dose of α-GPC in 12 normal volunteers. Citicoline (CTC), which also acts as a choline precursor, was included for comparison purposes. Each subject was studied on three randomized occasions, (i) in a control day in the absence of drug administration (to evaluate the plasma level profile of endogenous choline), (ii) after i.m. α-GPC (1,000 mg) and (iii) after i.m. CTC (1,000 mg) respectively, with a wash-out period of at least 1-week between sessions. Blood samples for plasma choline HPLC determinations were collected at regular intervals over a 6 h period. In the control session, plasma choline levels remained stable during the sampling period. The administration of α-GPC was associated with a rapid rise in plasma choline, peak levels being usually observed at the first (0.25 h) or second (0.5 h) sampling time after the injection. Thereafter, the concentration of choline declined gradually and returned to near baseline values at the end of the observation period. After the administration of CTC, plasma choline levels showed a similar time course but were considerably lower than those observed after the administration of α-GPC. Pharmacokinetic parameters calculated after subtracting the zero time concentration from all post-drug values indicated that exogenously derived choline declined in plasma with a half-life of 0.5 to 6.2 h, without any significant difference between α-GPC or CTC. Choline AUC values after α-GPC were significantly higher than those observed after CTC, but the difference was no longer significant when AUCs were corrected for the different choline content of the two preparations (405 mg for α-GPC vs 213 mg for CTC). It is concluded that the i.m. administration of α-GPC provides an effective means of increasing plasma choline levels.
The other mechanisms suggested to be involved in the neuroprotective effects of citicoline in stroke models include prevention of activation of phospholipase A2 (PLA2) [38]. The related effects comprise attenuation of the increase in hydroxyl radical generation, preventing loss of cardiolipin (an exclusive inner mitochondrial membrane phospholipid essential for mitochondrial electron transport, which is degraded in response to cellular insults and disrupts the mitochondrial respiratory chain). In aged rats, an increase in the brain level of platelet-activating factor (a bioactive phospholipid implicated in neuronal excitotoxic death) has also been noted [39]. In rats, attenuation of mitogen-activated protein kinases (MAPKs) and caspase activation have been observed following citicoline administration [40, 41]. Last, but not least, according to the most recent report [42], treatment with citicoline has been found to increase sirtuin-1 (SIRT1) protein levels in cultured neurons, in circulating blood mononuclear cells and in the brain. This effect seems to be of critical importance for neuroprotection in experimental stroke because sirtinol, a specific inhibitor of SIRT1 which, by itself, does not influence infarct volume, has been shown to abolish the neuroprotection offered by citicoline. Citicoline displayed a potent synergistic effect with resveratrol (which is known to be a SIRT1 activator), leading to a 60 % reduction in the experimental infarct volume in rats when both drugs were used in doses that were individually ineffective. Moreover, citicoline was ineffective in SIRT1 knock-out homozygotic mice subjected to focal brain ischaemia. However, detailed mechanistic explanations for all of these effects are lacking. For example, there is no explanation as to how citicoline administration leads to attenuation of MAPK activity and increases sirtuin-1 protein content in brain tissues; in particular, does the drug act extracellularly, or is resynthesis of CDP-choline inside brain cells a prerequisite? 2ff7e9595c
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