Evaluation of neuromodulatory effects of long-term treatment with citicoline in patients with cerebral small vessel disease

Background. Cerebral small vessel disease (CSVD) is a common pathology resulting from damage to small cerebral vessels, leading to chronic brain ischemia. CSVD is associated with 25 % of ischemic strokes and 45 % of vascular dementia cases. The main symptoms of CSVD include memory impairment, attention deficits, mood swings, gait disturbances, and neuropsychiatric disorders. Pharmacological approaches to treating CSVD are poorly studied and based on a limited number of low-quality studies. Citicoline is a neuroprotective agent used to improve cognitive functions and support neuronal structure. As a precursor of phosphatidylcholine, it helps stabilize cell membranes, reduce ischemic damage, and maintain neuronal structural integrity. It also stimulates the synthesis of acetylcholine, an important neurotransmitter in memory and learning processes. Several studies and meta-analyses have demonstrated the positive effects of citicoline on cognitive, emotional, and behavioral disorders which are often associated with CSVD. This makes citicoline a promising agent for CSVD therapy. To assess its clinical efficacy during long-term (20-day) use in patients with cerebral small vessel disease, a population study titled “Evaluation of neuromodulatory effects during long-term citicoline treatment in patients with CSVD” is starting. Objective: to confirm the clinical efficacy and safety of long-term use of citicolin in the treatment of patients with chronic cerebral vascular disorders (cerebral small vessel disease). Materials and methods. This clinical study is conducted as a multicenter post-registration observational (non-interventional) open-label non-comparative clinical trial. Patients undergo multimodal, clinical, and paraclinical examinations. All patients receive the best standard medical management according to national guidelines and standards approved by the Ministry of Health at the time of the study. Patient population. Patients with chronic cerebral vascular disorders (cerebral small vessel disease) will be included in selected centers in Ukraine. Efficacy criteria and variables. The main variable is the reduction in symptom intensity or cessation, and improvement in the overall condition. Primary efficacy endpoints of the investigational drug. The primary endpoint is the examination using the Hospital Anxiety and Depression Scale and Montreal Cognitive Assessment, conducted by a physician in outpatient practice to increase the level of evidence for citicolin before and after the therapy. Secondary efficacy endpoints of the investigational drug. The secondary endpoints were efficacy of the intervention and safety, tolerability of the drug; changes in concomitant symptoms. Conclusions. Cerebral small vessel disease is a common pathology. Pharmacological approaches to treating CSVD are poorly studied and based on a limited number of low-quality research. Studies have shown that the use of citicoline in appropriate doses is well tolerated and reduces the severity of cognitive, emotional, and behavioral disorders, which are common symptoms of CSVD. The study of the efficacy, safety, and tolerability of citicolin in the treatment of patients with cerebral small vessel disease will improve understanding of the role of neuroprotective therapy in the course of this pathology.