Clinical Trial of Efficacy and Safety of Divaza in the Management of Oxidative Disturbances in Cerebral Atherosclerosis
Clinical Trial of Efficacy and Safety of Divaza in the Management of Oxidative Disturbances in Cerebral Atherosclerosis
The purpose of this study is to obtain further data on the efficacy and safety of Divaza
 therapy for oxidative impairment elimination in patients with cerebral atherosclerosis.

 It is assumed that the inclusion of the drug Divaza in the basic therapy will help reduce the
 severity of cognitive disorders, other clinical symptoms of cerebral atherosclerosis, reduce
 the impact of the disease on the quality of life of the patient.

 Participate in the study may be patients with a diagnosis of "cerebral atherosclerosis",
 which, against the backdrop of basic therapy with constant doses of drugs (within the last 4
 weeks), to achieve a stable course of cerebral atherosclerosis, cognitive disorders without
 significant disability are detected.
The diagnosis of "cerebral atherosclerosis" is established in the presence of all three
 causes: a) the main vascular disease and focal neurological symptoms in combination with
 cerebral symptoms; b) ultrasound signs of atherosclerotic lesion of the cerebrovascular bed
 (according to data of duplex scanning of the main arteries of the head (MAG)) made in the
 previous 6 months before the patient was included in the study); c) signs of morphological
 changes in the brain substance from the data of neuroimaging.

 At cerebral atherosclerosis against the background of progressive oxidant disorders, the
 change in the mean value of resistance of lipoproteins (LP) to lipid peroxygenation (LPO)
 will be evaluated by the method of Fe2 + -induced chemiluminescence, high specificity and
 informativity of which was shown in the study of oxidative and antioxidant systems of
 patients with initial manifestations of chronic cerebrovascular insufficiency.

 The average value of resistance of LP to LPO will be determined in the laboratory initially
 and after 12 weeks of treatment.

 Cognitive disorders are significant clinical manifestations of chronic cerebrovascular
 disease with oxidative disorders, which significantly reduces the quality of life of
 patients. Changes in cognitive function will be assessed initially and after 12 weeks of
 treatment by the Montreal Cognitive Assessment (MoCA).

 As additional parameters, changes in the mean values of the levels of pre-formulated products
 of LPO, the ability of LP to oxidation, NO in serum, platelet aggregation and Carotid
 Intima-Media Thickness (CIMT) at 12 weeks of therapy as compared to the baseline condition.
Inclusion Criteria:

 1. Patients of either sex, aged 40-75 years.

 2. Diagnosis of cerebral atherosclerosis based on the following three factors:

 -  underlying vascular disease (atherosclerosis and/or arterial hypertension) and
 focal neurological signs and symptoms accompanied by nonspecific cerebral
 symptoms (i.e. headache, dizziness, noise in the head, impairment of memory,
 fatigue);

 -  ultrasound signs of cerebrovascular blood flow defects (on duplex scanning of the
 main artery of the head for 6 months before to study entry);

 -  1.0-1.5T CT/MRT signs of structural changes in brain matter (subcortical and
 periventricular leukoaraiosis and/or focal changes in gray and white matter
 observed as postischemic cysts and/or lacunar infarcts, and/or diffuse atrophic
 changes observed as ventricular or subarachnoid enlargement).

 3. Cognitive impairments (MoCA (Montreal Cognitive Assessment) <26).

 4. Patients who have been on an unchanged standard medication regimen for cerebral
 atherosclerosis and arterial hypertension for the previous month.

 5. Agreement to use a reliable method of birth control for the duration of the study.

 6. Provision of signed patient information sheet and informed consent form to participate
 in the clinical trial.

 Exclusion Criteria:

 1. A prior history of subarachnoid/parenchymatous/ventricular hemorrhage, brain neoplasm,
 or any other condition known to have caused the neurological dysfunction.

 2. Ischemic stroke or any other cerebrovascular accident defined by the Modified Rankin
 Scale (mRs > 1), within 6 months prior to study entry .

 3. Any known potential cardiac sources of embolism defined by TOAST as medium- to
 high-risk.

 4. Any previous (within 2 weeks prior to screening) or current signs of an acute
 infectious disease or exacerbation of a chronic infectious disease.

 5. Prior history of CNS (central nervous system) disorders, including:

 -  Inflammatory diseases of the CNS (G00-G09).

 -  Systemic atrophies primarily affecting central nervous system (G10-G13).

 -  Other degenerative diseases of the nervous system (G30-G32).

 -  Demyelinating diseases of the CNS (G35-G37).

 6. Dementia (F00-F03).

 7. Prior diagnosis of heart failure defined by the New York Heart Association
 classification (1964) as III or IV FC.

 8. Hypothyroidism, diabetes mellitus, or other decompensated somatic disease.

 9. Uncontrolled arterial hypertension: systolic blood pressure > 180 mm Hg and/or
 diastolic blood pressure > 110 mm Hg.

 10. Decompensated disease of veins of lower extremities (e.g. varicose veins of lower
 extremities, thrombosis of deep veins, etc.).

 11. Any other condition which, in the opinion of the investigator, prevents the patient
 from participating in the study.

 12. Any known or suspected malignant neoplasm.

 13. Allergy to/intolerance of any constituent of the medications used in the treatment.

 14. Hereditary lactose intolerance.

 15. Malabsorption syndrome (lactose intolerance), including congenital or acquired lactase
 deficiency or any other disaccharidase insufficiency, galactosemia.

 16. Pregnancy, breast-feeding.

 17. Prior history of non-adherence to a drug regimen, a psychiatric disorder, alcoholism,
 or drug abuse, which, in the opinion of the investigator, can compromise compliance
 with study protocol.

 18. Use of any medicine listed in the section "Prohibited concomitant treatment" within 1
 month preceding the inclusion in this study.

 19. Participation in other clinical trials within the 3 months preceding the inclusion in
 this study.

 20. Patient is related to the research personnel of the investigative site that are
 directly involved in the trial, or is the immediate relative of the investigator. The
 immediate relative includes husband/wife, parents, children or brothers (or sisters),
 regardless of whether they are natural or adopted.

 21. Patient works for OOO "NPF "Materia Medica Holding" (i.e. is the company's employee,
 temporary contract worker or appointed official responsible for carrying out the
 research or is an immediate relative of the aforementioned).