Algorithms for the treatment of patients with chronic cerebral ischemia of stages I and II with use of Picamilon: results of an open clinical comparative study

Aim. To study the efficacy and safety of Picamilon in patients with stages I and II of chronic cerebral ischemia (CCI).

Materials and methods. An open comparative clinical trial included 100 patients who were divided into 2 groups depending on the stage of CCI: n=50 (group 1 with CCI stage I); n=50 (group 2 with CCI stage II, average age 62.2±8.98 years). Group 1 patients were also divided into subgroups 1A (mean age 55.6±6.76 years) and 1B (mean age 52.8±6.11 years), which used different treatment regimens. The patients were prescribed the drug Picamilon, the total duration of therapy in group 1 was 60 days, in group 2 – 70 days. The study included 4 visits: before treatment, 10 days later, at the end of therapy (60/70 days later), 1.5 months after the end of treatment. The study was conducted using the Montreal Cognitive Function Assessment Scale (MoCA), the A.M. Wein scale of autonomic disorders, the A.I. Fedin scale of neurological disorders, and the Ya.I. Levin Sleep Quality Scale. The condition of cerebral blood flow (Dopplerography of intracranial vessels) and endothelial function (levels of methylated forms of arginine – ADMA, MMA, SDMA and their ratios) were assessed. Adverse events on the background of therapy and the tolerability of treatment were recorded.

Results. During treatment, statistically significant cognitive improvement on the MoCA scale (p=0.022 and p<0.0001) was observed in groups of patients with different stages of CCI, increasing in the delayed period: more than 80% of patients in the general sample reached the normal level when assessed in the long-term period. Patients with CCI II initially have a worse cognitive status, while their average score growth is significantly higher compared to CCI I. Autonomic symptoms significantly decrease, regardless of the stage of CCI and the treatment regimen: improvement in 29% and 38% of patients with CCI stages I and II, respectively. Positive dynamics of neurological functions was noted in 77% (CCI I) and 84% (CCI II) of patients, the effect of treatment increases in the delayed period (p<0.05). Patients with CCI II initially have a more pronounced neurological deficit, however, during treatment, the average decrease on the CCI Fedin A.I. scale is statistically significantly higher (p=0.037) than in patients with CCI I. In both groups of patients, there is a statistically significant comparable positive trend (decrease) in the severity of sleep disorders, increasing in the delayed period. In subgroup 1B (with parenteral therapy at the start), 28% of patients improved sleep quality by Visit 2 compared to 11% in subgroup 1A, and by the end of the course of therapy (Visit 3), the effect in the groups was comparable. The majority of patients (98%) noted good tolerability and comfort of therapy, while the groups and subgroups did not differ (p>0.05). Picamilon has an effect on cerebral hemodynamic parameters: against the background of therapy, the proportion of patients who have achieved normalization of hemodynamic parameters increases: up to 100% when assessing Vmax and resistance index and up to 93% when assessing pulsation index; the thickness of the intimate media complex is significantly reduced. Picamilon reduces concentrations of markers of endothelial dysfunction – initially elevated levels of ADMA in both groups and SDMA in group 2.

Conclusion. The use of Picamilon is effective in patients with stages I and II CCI, contributes to significant regression of cognitive impairment, neurological deficit, improvement of sleep quality and stabilization of autonomic function; improves vascular endothelial function, reduces the risk of atherosclerosis and cardiovascular complications in patients. The optimal duration of Picamilon therapy in CCI is 2–2.5 months, depending on the stage of the disease.