Efficacy and Safety of Divaza for the Correction of Oxidative Disturbances in Patients with Cerebral Atherosclerosis: A Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to determine if Divaza, a drug with nootropic and antioxidant effects, was safe and effective for the correction of oxidative disturbances and to stabilize cognitive impairment in patients with cerebral atherosclerosis. STUDY DESIGN: The study design consisted of a 12-week multicenter, randomized, double-blind, placebo-controlled, prospective trial in parallel groups. SETTING: The setting in which the study was conducted comprised 10 clinical centers across the Russian Federation. INTERVENTIONS: Patients were randomized into 2 groups and instructed to take either 2 tablets of the study drug or a placebo 3 times per day in conjunction with basic therapy. OUTCOMES: The primary outcome was a change in the average endogenous antioxidant potential after the completion of the study. The blood indicators of the oxidative stress (OS) were analyzed at the baseline and then after 12 weeks of therapy using iron-induced chemiluminescence analysis. The Montreal cognitive assessment test was used as a secondary outcome measure to evaluate cognitive impairment at the end of the study. RESULTS: 124 outpatients with a mean age of 60.7 ± 7.6 years were enrolled and randomly assigned to receive Divaza (n = 65) or a placebo (n = 59). An improvement of cognitive function was observed in all patients of the Divaza group at the end of the treatment; this was significantly better than the placebo group (100 [100] vs. 89.5 [89.1]%, respectively, p = 0.0272 [p = 0.0128]). The administration of Divaza restored the activity of the endogenous antioxidant system. The change in the average level of lipoprotein resistance to oxidation after 12 weeks of therapy, compared to the baseline, was significantly higher in the Divaza group (14.8 ± 14.7 [14.8 ± 14.7] seconds latent period vs. 6.4 ± 16.9 [6.9 ± 16.7] seconds in the placebo group (p = 0.007 [p = 0.0107]). CONCLUSIONS: Divaza is a safe and effective therapeutic option for attenuating OS and recovery of cognitive impairment in patients with cerebral atherosclerosis.

Treatment of Cognitive Impairment and the Role of Demographic Factors in Disease Progression: The Final Results of the Russian Observational Program "DIAMANT".

BACKGROUND: Chronic cerebral ischemia (CCI) is a form of cerebrovascular disease manifested as a vascular cognitive impairment (VCI). The management of the patients with CCI is determined by a healthy lifestyle and early therapy aimed at correcting and preventing this disease. Divaza is a drug with endothelial protective and nootropic effects. We present the final efficacy and safety analysis of all-Russian, open-label, prospective, observational, multicenter study of Divaza and emphasize the role of demographic and socioeconomic factors in cognitive disorder (CD) progression. METHODS: CCI patients (n = 2,583) with or without CD were enrolled. Patients received Divaza (2 tablets 3 times per day for 12 weeks). Montreal Cognitive Assessment (MoCA) testing was required. The change in the mean MoCA score post-treatment was used as the primary endpoint. As the secondary endpoints, the number of patients with a MoCA <26 and ≤17 (dementia); the percentage of patients with a MoCA score improvement in different age groups; the dynamics of mean MoCA score in age groups; and the relationship between CD and sex or regional social/economic factors were assessed. RESULTS: Divaza therapy led to a significant improvement: the mean MoCA score was up to 20% higher post-treatment (Wilcoxon test, p < 0.0001 vs. baseline). The number of participants with MoCA ≥26 increased by 33.6%. The number of patients with dementia was 4.1 times less after therapy (p < 0.00001 vs. baseline). Divaza improved cognitive functions of patients in each age group. Findings demonstrate that regional socioeconomic factors contribute to CD development and severity. The observed divergence between sexes was a result of a larger number of women enrolled. The study confirmed the safety of Divaza. CONCLUSIONS: In the study, we observed the efficacy of Divaza for the treatment of CD: a therapy contributed to an increase in the mean MoCA score and the positive dynamics in the number of patients with cognitive improvement.

Endothelial dysfunction a significant marker of adverse clinical outcome in patients with atrial fibrillation after cardioembolic stroke.

AIM: To study the prognostic significance of endothelial dysfunction (ED) markers in the development of adverse clinical outcome (death) in patients with atrial fibrillation (AF) within a year after cardioembolic stroke. MATERIALS AND METHODS: 260 patients with newly diagnosed (nAF), paroxysmal, persistent and permanent forms of AF who underwent stroke were included. Duration of observation-12 months. V1 - the beginning of the study: V2 - 180 (±5) days and V3 - 360 (±5) evaluated the level of von Willebrand factor (fW), antithrombin III (AT III) and plasminogen. RESULTS: During the year of follow-up, patients with AF who underwent and had a high mortality rate. During the whole period 38 (14.6%) patients died, 15 (23.0%) - in the group with nAF, 6 (9.2%) - in the group with paroxysmal AF, 7 (10.8%) - in the group with persistent AF and 10 (15.4%) - in the group with permanent AF. After a year of follow-up, the level of fW in patients with nAF was higher than in patients of all groups, and statistically significant in patients with paroxysmal and persistent forms of AF. At III was important in the group of patients with nAF and with a constant form of AF, in the same groups there was no statistically significant increase in a year of follow-up. It was found that in survivors with nAF at III (73.54±8.67%) higher (p=0.002) compared with the dead (65.77±6.01%). In the group of patients with paroxysmal AF in survivors of III (77.75±10.15%) higher (p=0.031) compared with the dead (69.25±5.80%). In patients with persistent AF, the survivors of III (76.57±9.09%) were higher (p=0.002) compared to the dead (65.60±2.21%). Taking into account the results of the analysis of the dynamics of ed markers, it can be assumed that AT III is the most accurate prognostic marker for the studied cohort of patients. CONCLUSION: Detection and correction of ED in AF in patients within a year after stroke can optimize the tactics of management of patients and improve the prognosis of the diseas.

The Use of Release-Active Antibody-Based Preparations for Vertigo Prevention in Adults.

The effectiveness of antibody-based release-active preparations Impaza (antibodies to eNOS), Tenoten (antibodies to brain-specific protein S-100), Dietressa (antibodies to type 1 cannabinoid receptor), Brizantin (combined preparation, antibodies to brain-specific protein S-100 and type 1 cannabinoid receptor), and Divaza (combined preparation, antibodies to brain-specific protein S-100 and eNOS) in the prevention of vertigo was studied on the model of intermittent accumulation of Coriolis accelerations (ICCA). Modification of activity of vestibular receptors and signal systems by release-active preparations contributed to an increase in ICCA tolerance time. Combined preparation Impaza possessed the most significant antinaupathic properties. Brizantin was less potent in this respect.

Anxiolytic and Antidepressant Effects of Divaza and Brizantin.

The anxiolytic and antidepressant activities of complex preparations divaza and brizantin containing antibodies to brain-specific protein S100 were estimated using Vogel conflict test and Nomura forced swimming test. Course treatment (5 days) of brizantin in a dose of 2.5 ml/kg and divaza in a dose of 7.5 ml/kg significantly increased punished drinking in the Vogel conflict test in comparison with the control. Both drugs also improved general emotional behavior during training prior to the test procedure. Brizantin and divaza in a dose of 7.5 ml/kg increased the number of wheel revolutions in the Nomura forced swimming test in comparison with the control; the effect of divaza was more pronounced. High correlation coefficients between the number of wheel revolutions during the first and second 5-min sessions are also indicative of antidepressant action of divaza and brizantin.

[Diagnosis and treatment of cognitive impairment in patients with chronic cerebral ischemia: the results of observational Russian program DIAMANT]. / Diagnostika i lechenie kognitivnykh narushenii u patsientov s khronicheskoi ishemiei golovnogo mozga: rezul'taty Vserossiiskoi neinterventsionnoi nabliudatel'noi programmy DIAMANT.

AIM: To investigate the efficacy of divaza in outpatients with cognitive disorders and chronic brain ischemia (CBI). MATERIAL AND METHODS: The non-interventional observational program included the data of 2583 outpatients with CBI from 30 cities (8 federal okrugs of the Russian Federation) who were on outpatient neurological treatment and received divaza in a dose of 2 tablets three times a day from Oct 2016 to Jan 2017. Cognitive functions were evaluated using the MoCA scale before and after 3 months of treatment. RESULTS AND CONCLUSION: Cognitive disorders were identified in 90.7% of patients (<26 MoCA scores). After treatment, the mean MoCA score increased from 19.58±5.13 to 23.99±4.21 (p<0.0001), the number of patients with normal cognitive functions rate (≥26 scores) increased from 9.3 to 41.3%, the number of patients with marked cognitive impairment decreased. The drug was well-tolerated by old and very old patients, adverse events were observed rarely (0.6% of cases). The majority of doctors (88.4%) noticed the effect of divaza as significant improvement or improvement, and 89.6% of patients valued the effect to be excellent or good. The use of divaza, the drug with endothelioprotective and nootropic effects, is pathogenetically justified and promising in patients with cognitive disorders of vascular etiology.

[Cerebral markers of endothelial dysfunction in chronic brain ischemia]. / Markery éndotelial'noi disfunktsii pri khronicheskoi ishemii mozga.

A review of the main markers of endothelial dysfunction in chronic cerebral ischemia is presented. The quantitative changes in the level of endothelial dysfunction markers in chronic cerebral ischemia help to evaluate the efficacy of preventive and therapeutic pharmacological activities. The results of clinical trials have demonstrated that the course use of divazа in patients with chronic cerebral ischemia leads to improvement of both clinical indicators and laboratory markers for normalization of cerebral ischemia and endothelial dysfunction.

[Divasa in the treatment and prevention of cerebrovascular diseases]. / Divaza v terapii i profilaktike tserebrovaskuliarnykh zabolevanii.

Disturbances of hemorheology, hemostasis and fibrinolysis play an important role in the pathogenesis and pathophysiology of chronic cerebral ischemia. Physiological functioning of the endothelium is disturbed under the action of damaging factors. Divaza is created on the basis of release-active antibodies to S100b protein and antibodies to endothelial NO-synthase. The efficacy of divaza in the treatment of chronic cerebral ischemia and related diseases (cognitive impairment, anxiety) was demonstrated. A normalizing effect of divaza in the dose of 2 tablets 3 times daily between meals during 12 weeks on endothelial function is shown.

[Results of multicenter study of efficacy and safety of divaza in the treatment of the asthenic and mild to moderate cognitive disorders in elderly and senile subjects]. / Rezul'taty mnogotsentrovogo issledovaniia éffektivnosti i bezopasnosti primeneniia preparata divaza pri astenicheskikh i legkikh ili umerennykh kognitivnykh rasstroistvakh v pozhilom i starcheskom vozraste.

AIM: To study the efficacy and safety of divasa in elderly and senile subjects with asthenic and mild to moderate cognitive disorders. MATERIAL AND METHODS: The study included 126 patients with clinically significant asthenia and mild to moderate cognitive disorders. Asthenia was assessed with MFI-20, cognitive disorders with MMSE, clock drawing test and verbal association test. All patients were treated with divasa in dose 2 tablets 3 times a day. RESULTS AND CONCLUSION: The efficacy and safety of divasa in asthenic and mild to moderate cognitive disorders in elderly and senile subjects were shown. There is a need for a multicenter placebo-controlled trial on the efficacy of divasa to treat cognitive and asthenic disorders in elderly patients.