Clinical trials

This is a multi-center, cross-sectional, observational study aimed at developing biological age calculators specifically for the Russian population investigating various aging phenotypes. Aging is a complex process that varies greatly between individuals, meaning that chronological age does not always reflect one's biological health status. The primary goal of this study is to identify and analyze a comprehensive set of markers (including socioeconomic factors, lifestyle, physical parameters, cognitive function, and laboratory biomarkers) that best reflect the aging process. Using this data, researchers will create a mathematical model to estimate a person's "biological age." The study plans to enroll at least 3,500 male and female volunteers aged 18 years and older from across Russia. Participants will be divided into 5-year age groups (e.g., 18-24, 25-29, up to 90+ years) to ensure broad representation. Participation involves a single visit to a clinical center. During this visit, participants will undergo: Interview and questionnaires (assessing health history, lifestyle, socioeconomic status, diet, sleep, and quality of life). Physical examination and anthropometric measurements (height, weight, blood pressure, grip strength). Functional and cognitive tests (e.g., walking speed, balance tests, memory and attention tasks tailored to age). Collection of biomaterials: blood (50 ml), urine, and stool samples for extensive laboratory analysis, including routine tests and specialized aging biomarkers. Part of the biomaterials will be biobanked for future scientific research. Instrumental examinations for a subset of participants: Depending on the center's capabilities and the study protocol, some participants may also undergo additional assessments such as densitometry (bone density scan), bioimpedance analysis (body composition), and brain MRI. The results are expected to lead to the creation of a validated biological age calculator for the Russian population. This tool could help identify targets for interventions to promote healthy aging and, in the future, potentially predict the risk of developing age-related chronic diseases.

The study is planned to evaluate the effectiveness and safety of two types of anesthesia (regional and general) for carotid endarterectomy in 100 patients with acute stage of stroke: 50 patients will be operated under regional anesthesia and the remaining 50 patients under general anesthesia. Patient inclusion criteria: 1. Ischemic stroke in the middle cerebral artery territory 2. Ipsilateral stenosis of the internal carotid artery more than 50% 3. Neurological deficit at the time of surgical treatment: the modified Rankin scale (mRs) score of 0-4 and the US National Institutes of Health (NIHSS) stroke scale score no more than 12 4. The size of the ischemia focus: no more than 1/3 in the territory of the middle cerebral artery brain supply 5. Terms of operation: from 1 to 28 days from the moment of ischemic stroke The primary intra-hospital and/or 30-day study endpoints: 1. Perioperative ipsilateral ischemic stroke. 2. Any stroke: contralateral ischemic or any hemorrhagic stroke. 3. Myocardial infarction. 4. Hemorrhagic complications that required surgical revision of the operating wound or transfusion of blood components. 5. Surgical site infection 6. Death 7. Main adverse cardiovascular events (stroke + myocardial infarction + death).

The objective of this randomized clinical trial is to evaluate the safety and efficiency of different anticoagulation schemes with heparin for venous thromboembolism prevention in patients with hypertensive intracerebral hemorrhage. The main questions it aims to answer are: * What is the optimal time for the beginning of anticoagulation with heparin to efficiently prevent venous thromboembolism in patients with hypertensive intracerebral hemorrhage? Early beginning (within the first 2 days but not earlier than 12 hours after the admission of a patient) or delayed beginning (on the third day after the admission of a patient)? * Which of the two timeframes (early or delayed) for anticoagulation beginning is the most safe in terms of bleeding complications including intracerebral hemorrhage expansion? Researchers will compare the results of early and delayed start of anticoagulation using heparin in patients with hypertensive intracerebral hemorrhage to define the optimal start time for anticoagulation that provides the most favourable efficiency/safety profile. Participants will: * Undergo a computed tomography (CT) scan of the brain on hospital admission and then 12-24 hours after the hospital admission and 24 hours after the beginning of venous thromboembolism prophylaxis using heparin; * Undergo the ultrasound examination of lower extremity deep veins on hospital admission and then once every 7 days; * Receive prophylactic doses of low molecular weight heparin or unfractionated heparin either beginning within the first 2 days but not earlier than 12 hours after the hospital admission or starting on the 3rd day after the hospital admission.

Technically successful laser crossectomy will reduce the risk of reflux recurrence at the sapheno-femoral junction without increasing the risk of endovenous heat-induced thrombosis, which may positively impact the likelihood of ultrasound- or clinical-recurrence of varicose veins. Similar technical efficacy is expected for laser crossectomy at 1940 nm and 1470 nm. A possible advantage of the 1940 nm wavelength in terms of postoperative pain intensity and the risk of adverse events cannot be ruled out.

The aim of the study is to make a validation of Caprini score in patients undergoing varicose veins surgery, especially endovascular procedures (endovascular laser treatment - EVLT, radiofrequency ablation - RFA, ultrasound-guided foam sclerotherapy - USFS) and to identify patients with elevated risk of postoperative venous thromboembolism (VTE) who will benefit from prophylactic anticoagulation.

The goal of this clinical trial is to evaluate the efficacy and safety of the investigational drug ASO-GNAO1 (Tianasen) in pediatric patients with c.607G\>A mutation in the GNAO1 gene associated with epilepsy and neurodevelopmental disorder. The main questions it aims to answer are: 1. Does intrathecal administration of ASO-GNAO1 slow or halt the progression of motor and cognitive symptoms? 2. Is ASO-GNAO1 safe and well-tolerated in this patient population? 3. What is the appropriate therapeutic dose? This is an open-label study without a placebo control group due to the rare and severe nature of the disease. All participants will receive the active drug. Participants will: Receive escalating doses of ASO-GNAO1 via intrathecal injection over a 12-month period. Undergo frequent neurological assessments, biomarker testing, and safety monitoring.

Type 1 diabetes (T1D) is caused by destruction of pancreatic islet beta-cells that produce insulin - the hormone required for glucose uptake by body tissues and organs. Since loss of beta-cells leads to insulin deficiency, blood glucose increases and the symptoms of T1D (thirst, hunger, excessive urination) appear. Inability of patient's tissues and organs to utilize glucose results in rapid weight loss and life-threatening acute T1D complications - ketosis and coma. To ensure glucose consumption by tissues and organs and to prevent acute complications, all patients with T1D need lifelong therapy with insulin. Insulin therapy is also necessary to prevent long-term T1D complications (eye, renal, nerve, and heart problems). By the time T1D is diagnosed, 80-90% of beta-cells have already been destroyed. However, 10-20% viable insulin-producing beta-cells remain in the pancreas over several months and even years after T1D diagnosis. The higher the percentage of the remaining beta-cells, the smaller the risk of long-term complications. Destruction of beta-cells in T1D has an autoimmune origin. It means that the patient's immune system, which is normally targeted at microbes, viruses, and other non-self substances, mistakenly destroys the beta-cells. The key role in this autoimmune reaction is played by specific cells of the immune system: T- and B-lymphocytes. T-lymphocytes directly damage the beta-cells, while B-lymphocytes support T-lymphocytes activity via antigen presentation mechanisms. Rituximab is a drug that specifically eliminates B-lymphocytes from the blood based on the CD20 surface molecule expressed on their surface, as a target. Notably, a subset of currently active T cells, including those potentially associated with pathogenesis of multiple sclerosis, also express CD20 marker on their surface. This makes them a potentially another critically important target of rituximab. In 2009 - 2014, a multicenter study in the U. S. and Canada showed that a single three-week course of rituximab infusions slightly but significantly had improved survival of residual beta-cells and their insulin-producing capacity in patients with recent-onset T1D. However, this beneficial action of rituximab lasted for only one year. We hypothesized that the repeated courses of rituximab performed over a period of 5 months could produce more profound and durable elimination of pathogenic B- and T- cells, and as a consequence prolonged survival of residual beta-cells and insulin secretion without serious adverse events. Testing this hypothesis is the goal of our study

Widespread introduction of high-resolution videocolonoscopy into clinical practice has led to an increase in the detection of epithelial lesions of the colon, a significant portion of which are small (\<10 mm) and miniature (≤5 mm) lesions. According to the literature, 15.6-27% of colon lesions 6-9 mm in size and 4.4-10% of those ≤5 mm are high-risk lesions, i.e. they contain villous structures, foci of severe dysplasia or cancer. One of the methods for removing such lesions is the technique of cold loop polypectomy (CLP), i.e. mechanical removal of the polyp with a loop without the use of electric current. This method is common for colon lesions 4-9 mm in size. (For smaller lesions, a technically simple and effective method of removing them using biopsy forceps is most often used) Jung YS, Park JH, Kim HJ et al. Complete biopsy resection of diminutive polyps. Endoscopy 2013; 45: 1024-9). A number of studies have demonstrated the advantages of the CP technique over standard removal methods. "Cold" polypectomy reduces the incidence of complications associated with thermal effects on the mucous membrane and underlying tissues (Bo-In Lee. Polypectomy of Small Polyps: Technical Updates. IDEN 2016, 280-281). Not only the number of perforations and manifestations of postcoagulation syndrome is reduced (D. von Renteln1, H. Pohl. Polyp Resection - Controversial Practices and Unanswered Questions. Clin Transl Gastroenterol. 2017 Mar; 8(3): e76. doi: 10.1038/ctg.2017.6), but also delayed bleeding: 0% with cold snare removal versus 0.5-14% after classical removal using electric current (Horiuchi A, Nakayama Y et al. Removal of small colorectal polyps in anticoagulated patients: a prospective randomized comparison of cold snare and conventional polypectomy. Gastrointest Endosc. 2014 Mar;79(3):417-23. doi: 10.1016/j.gie.2013.08.040; T. Kawamura1, Y.Takeuchi A comparison of the resection rate for cold and hot snare polypectomy for 4-9 mm colorectal polyps: a multicentre randomised controlled trial (CRESCENT study) Gut Online First, published on September 28, 2017 as 10.1136/gutjnl-2017-314215) ! It is also important that the removal of polyps with a cold snare takes less time than with a hot one, averaging 18 min. versus 25 min. (Ichise Y1, Horiuchi A, Nakayama Y, Tanaka N. Prospective randomized comparison of cold snare polypectomy and conventional polypectomy for small colorectal polyps. Digestion. 2011;84(1):78-81. doi: 10.1159/000323959. However, there are currently clearly not enough large multicenter prospective randomized studies devoted to the comparison of the efficacy and safety of "standard" and cold polypectomy. The opinion of specialists is also ambiguous regarding the instrumentation that should be used for endoscopic removal of small formations. Some endoscopists believe that the type of polypectomy snare used does not affect the efficacy, completeness and safety of removal of small formations, while others, on the contrary, pay special attention to the use of specially designed small-diameter snare loops, believing that only they are capable of ensuring the removal of formations in a single block in the vast majority of cases. (Horiuchi A, Hosoi K, Kajiyama M, et al. Prospective, randomized comparison of 2 methods of cold snare polypectomy for small colorectalpolyps. Gastrointest Endosc 2015;82:686-92.) The question of the need to inject fluid into the submucosal layer under the removed formation also requires a reasoned answer, given that many researchers skip this stage of the intervention and / or consider it unnecessary Toshiki Yamamoto, Sho Suzuki, Chika Kusano, Kyoko Yakabe, Maho Iwamoto, Hisatomo Ikehara, Takuji Gotoda, Mitsuhiko Moriyama. Histological outcomes between hot and cold snare polypectomy for small colorectal polyps. Saudi J Gastroenterol. 2017 Jul-Aug; 23(4): 246-252. doi: 10.4103/sjg.SJG\_598\_16

Venoactive drug (VAD) therapy is one of the most effective methods of treating chronic venous diseases (CVD). Numerous studies have proven its high efficacy in relieving symptoms of CVD, such as leg pain and swelling, leg heaviness and fatigue. Pelvic venous disorders (PeVDs) represent a group of pathological conditions including varicose veins of the pelvis and vulva, and compression stenoses of the left renal and common iliac veins. Although PeVDs are associated with venous lesions of the pelvis and retroperitoneum and have specific clinical manifestations, they are one of the forms of CVD and constitute a separate cohort. A number of studies on the VAD usage in PeVD indicate the wide possibilities of this type of treatment in eliminating chronic pelvic pain (CPP), the most dramatic symptom of PeVD, which is the main cause of disability and decreased quality of life, social and daily activity in women with PeVD. Currently, a variety of VADs are presented on the pharmaceutical market, which, according to the product labels, provide effects not only on the venous outflow from the lower extremities, but also on venous hemodynamics in the pelvis. At the same time, a literature analysis shows that micronized purified flavonoid fraction (MPFF) has the greatest evidence base obtained in the efficacy and safety studies of VADs in PeVD. Nevertheless, patients are rarely interested in the scientific dossier of drugs, and in the real practice the patients with PeVD and CPP most often ask: "What is the best drug to use for the CPP relief?" This is quite understandable, as it is CPP in PeVD that results not only in disability, but also in family conflicts, psycho-emotional stress and depressive states. In this regard, patients seek to get rid of pain as soon as possible and strive to use the most effective drug. An extensive scientific base of comparative studies on the use of various VADs in patients with CVD and PeVD has been accumulated to date. However, the literature is lack of any data on the comparative efficacy and safety of VADs in the treatment of patients with PeVD. This, in turn, makes not possible for doctors and patients to choose the optimal and most effective drug based on the objective research data. All the above has predetermined the purpose of the planned study as evaluating the efficacy and safety of different VADs in the treatment of female patients with PeVD.

Compression therapy is basic treatment for chronic venous disease (CVD) of the lower limbs. Numerous studies have demonstrated the efficacy and safety of compression therapy in relieving symptoms such as pain, venous edema, leg heaviness and fatigue, as well as accelerating the healing of venous ulcers. It has been established that сompression therapy is indicated for patients with both minimally expressed manifestations of CVD and severe forms of the disease. At the same only one study has been conducted to assess the correction of venous outflow from the lower limbs and pelvis in patients with pelvic varicose vein (PVV) and pelvic congestion syndrome (PCS). However, the incidence of this pathology ranges from 15 to 30% in the female population. The cost to the healthcare system of treating these patients in the United States exceeds $2 billion. To date, the options and indications for compression therapy in patients with concomitant PVV and CVD have not been defined. The rational use of compression in this cohort of patients may contribute to the improvement of effective conservative treatment. In addition, inappropriate prescription of compression to patients with pelvic venous disease (which can be observed in real clinical practice) may discredit this simple, effective and safe therapeutic method. In addition, the research devoted to the problem of compression treatment of PVV will contribute to the development of new special compression products aimed at accelerating venous outflow from the pelvic organs. It can be assumed that this will serve as a stimulus for obtaining new data on the therapeutic effects of compression and create conditions for the creation of new technological directions in the production of compression knitwear.