A Phase 4 interventional study of Divaza and Placebo in Cerebral Atherosclerosis, sponsored by Materia Medica Holding. Completed at 10 sites in Russian Federation. Open to participants aged 40 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-08-26.
Sponsored by Materia Medica Holding · Phase 4, Interventional, and Treatment
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The purpose of this study is to obtain additional data on efficacy and safety of Divaza for adjustment of oxidative disorders 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.
Design - a multicenter randomized double-blind placebo-controlled parallel-group clinical trial.
The study will enroll the patients of either gender aged 40-75 years old inclusively with verified atherosclerotic cerebrovascular lesions (ICD-10 code - "Cerebral atherosclerosis" [I67.2]), with cognitive disorders (МоСА\<26), without relevant incapacity (mRs≤1).
At screening visit (Visit 1, from day - 5 to day 0), after signing patient information sheet (informed consent form) for participation in the clinical study the patient's complaints and medical history will be collected and objective examination will be carried out. The investigator will assess intensity of cognitive disorders using MoCA, extent of functional capacity using mRs .
If the patient meets inclusion criteria and has no exclusion criteria at Visit 2 (Day 0) he/she will be randomized to one of two groups: group 1 will receive Divaza at 2 tablets 3 times a day; group 2 - placebo using study drug scheme.
Laboratory examination will be performed.
The first administration of Divaza or Placebo will be performed at Visit 2 at medical site in the investigator's presence. The patient monitoring and therapy will last for 12 weeks during which 3 additional visits will be made.
At Visit 3 (Week 4±5 days) the investigator will collect the complaints, perform objective examination, evaluate intensity of cognitive disorders (MoCA). The investigator will monitor the prescribed, basic and concomitant therapy, evaluate therapeutic safety.
At Visit 4 (Week 8±5 days) the investigator will make a phone call to the patient to evaluate safety of the treatment.
At the final Visit 5 (Weeks 12±5 days) the investigator will evaluate intensity of cognitive disorders (MoCA). Laboratory examination of oxidant and antioxidant systems, compensatory potential of endothelium and its potential for adequate vascular tone regulation. The investigator will monitor the prescribe, basic and concomitant therapy, evaluate therapeutic safety and treatment compliance.
During the study basic, concomitant therapy will be allowed except for the products indicated in the section "Prohibited concomitant therapy".
102 studies on the registry are indexed under Intracranial Arteriosclerosis; 48 are open to participants now.
This study's enrollment of 124 is below the median of 194 across 61 interventional studies indexed under Intracranial Arteriosclerosis.
Browse Intracranial Arteriosclerosis studies →Materia Medica Holding is the lead sponsor of 43 studies on the registry; 4 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Diagnosis of cerebral atherosclerosis verified by all three signs:
Exclusion Criteria:
History of CNS diseases including:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Drug: Divaza
Tablet for oral use. Two tablets per intake 3 times a day (approximately at the same time), outside of meal (between meals or 15 minutes before eating or drinking). The tablets should be held in mouth until completely dissolved.
Drug: Placebo
Oral administration.
Oral administration.
Change in Mean Value of Lipoprotein Resistance to LPO.
Based on laboratory evaluation. Change in the mean resistance of lipoprotein (LP) to lipid peroxidation (LPO) after 12-week therapy versus baseline.
Time frame: 12 weeks of the observation period.
Percentage of Patients With Improved Cognitive Function.
MoCA (Montreal Cognitive Assessment) score +1 and over after 12-week therapy versus baseline. Minimum score is 0, maximum score is 30. Higher values represent a better outcome.
Time frame: 12 weeks of the observation period.
Change in Mean Level of Preformed LP Products (Mainly Lipid Hydroperoxides).
Based on laboratory evaluation. Change in mean level of preformed LP products, predominantly lipid hydroperoxides after 12-week therapy versus baseline. The following kinetic parameters of chemiluminescence were measured: rapid chemiluminescence flare amplitude reflecting the stationary level of lipid hydroperoxides.
Time frame: 12 weeks of the observation period
Change in Mean Value of Lipoprotein Ability for Oxidation.
Based on laboratory evaluation. Change in mean value of lipoprotein ability for oxidation after 12-week therapy versus baseline. For plasma, draw blood into an EDTA tube and gently invert the tube 8 to 10 times to mix the anticoagulant. Centrifuge the tube, remove the stopper and draw off approximately 2/3 of the upper plasma layer into a labeled transfer tube using a transfer pipet bulb. Plasma must be separated from cells within 45 minutes of venipuncture. Measurement of oxidized LDL (oxLDL) has been incorporated into clinical practice in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases, especially as it pertains to the evaluation of oxidative stress. Oxidized LDL-particles are considered to be an important driving factor in the pathophysiology of atherosclerosis and oxLDL measurement has been used to test the efficacy of CVD drugs (eg, statins) to reduce oxidative stress.
Time frame: 12 weeks of the observation period.
Change in Mean Value of NO Products Serum Concentration.
Based on laboratory evaluation. Change in the mean concentration of nitrites and nitrates in serum after 12-week therapy versus baseline. Griess Reaction assay. In the Griess reaction, first reported by Johann Peter Griess in 1879 as a method of analysis of nitrite (NO2-), nitrite reacts under acidic conditions with sulfanilic acid (HO3SC6H4NH2) to form a diazonium cation (HO3SC6H4-Ntriple bondN+) which subsequently couples to the aromatic amine 1-naphthylamine (C10H7NH2) to produce a red-violet coloured (λmax ≈ 540 nm), water-soluble azo dye (HO3SC6H4-Ndouble bondN-C10H6NH2).
Time frame: 12 weeks of the observation period.
Change in Mean Value of Platelet Aggregation.
Based on laboratory evaluation. Change in mean platelet aggregation after 12-week therapy versus baseline.
Time frame: 12 weeks of the observation period.
| Milestone | Divaza | Placebo |
|---|---|---|
| Started | 65 | 59 |
| Completed | 64 | 59 |
| Not completed | 1 | 0 |
| Withdrew: Non-compliance with inclusion criteria | 1 | 0 |
Based on laboratory evaluation. Change in the mean resistance of lipoprotein (LP) to lipid peroxidation (LPO) after 12-week therapy versus baseline.
| seconds | Divaza | Placebo |
|---|---|---|
| Resistance of LP to LPO at baseline | 42.4 ± 13.1 | 42.9 ± 11.2 |
| Resistance of LP to LPO after 12 weeks | 55.6 ± 12.5 | 49.4 ± 14.3 |
| ∆ between baseline and after 12 weeks | 14.8 ± 14.7 | 6.4 ± 16.9 |
MoCA (Montreal Cognitive Assessment) score +1 and over after 12-week therapy versus baseline. Minimum score is 0, maximum score is 30. Higher values represent a better outcome.
| Participants | Divaza | Placebo |
|---|---|---|
| Percentage of Patients With Improved Cognitive Function. | 56 | 51 |
Based on laboratory evaluation. Change in mean level of preformed LP products, predominantly lipid hydroperoxides after 12-week therapy versus baseline. The following kinetic parameters of chemiluminescence were measured: rapid chemiluminescence flare amplitude reflecting the stationary level of lipid hydroperoxides.
| Mcmol / L | Divaza | Placebo |
|---|---|---|
| Level of preformed LPO products at baseline | 72.5 ± 14.1 | 72.8 ± 12.9 |
| Level of preformed LPO products after 12 weeks | 67.7 ± 13.1 | 69.9 ± 11.7 |
| ∆ between baseline and after 12 weeks | -3.2 ± 9.6 | -2.9 ± 8.0 |
Based on laboratory evaluation. Change in mean value of lipoprotein ability for oxidation after 12-week therapy versus baseline. For plasma, draw blood into an EDTA tube and gently invert the tube 8 to 10 times to mix the anticoagulant. Centrifuge the tube, remove the stopper and draw off approximately 2/3 of the upper plasma layer into a labeled transfer tube using a transfer pipet bulb. Plasma must be separated from cells within 45 minutes of venipuncture. Measurement of oxidized LDL (oxLDL) has been incorporated into clinical practice in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases, especially as it pertains to the evaluation of oxidative stress. Oxidized LDL-particles are considered to be an important driving factor in the pathophysiology of atherosclerosis and oxLDL measurement has been used to test the efficacy of CVD drugs (eg, statins) to reduce oxidative stress.
| mV | Divaza | Placebo |
|---|---|---|
| LP ability for oxidation at baseline | 1027.3 ± 204.7 | 993.8 ± 264.1 |
| LP ability for oxidation after 12 weeks | 1024.1 ± 226.7 | 1040.6 ± 217.7 |
| ∆ between baseline and after 12 weeks | -12.1 ± 192.1 | 57.0 ± 241.5 |
Based on laboratory evaluation. Change in the mean concentration of nitrites and nitrates in serum after 12-week therapy versus baseline. Griess Reaction assay. In the Griess reaction, first reported by Johann Peter Griess in 1879 as a method of analysis of nitrite (NO2-), nitrite reacts under acidic conditions with sulfanilic acid (HO3SC6H4NH2) to form a diazonium cation (HO3SC6H4-Ntriple bondN+) which subsequently couples to the aromatic amine 1-naphthylamine (C10H7NH2) to produce a red-violet coloured (λmax ≈ 540 nm), water-soluble azo dye (HO3SC6H4-Ndouble bondN-C10H6NH2).
| μmol per liter | Divaza | Placebo |
|---|---|---|
| NO-3 level at baseline | 41.3 ± 14.9 | 69.0 ± 28.9 |
| NO-3 level (after cuff test) at baseline | 38.4 ± 16.5 | 79.1 ± 33.5 |
| NO-3 level after 12 weeks | 51.7 ± 23.9 | 63.3 ± 36.8 |
| NO-3 level (after cuff test) after 12 weeks | 64.0 ± 15.6 | 61.1 ± 27.9 |
| NO-2 level at baseline | 35.9 ± 16.0 | 62.8 ± 28.0 |
| NO-2 level (after cuff test) at baseline | 31.8 ± 16.1 | 69.6 ± 32.3 |
| NO-2 level after 12 weeks | 43.9 ± 22.2 | 52.5 ± 35.9 |
| NO-2 level (after cuff test) after 12 weeks | 57.0 ± 14.5 | 51.0 ± 25.9 |
| NO level at baseline | 5.4 ± 2.3 | 6.3 ± 4.1 |
| NO level (after cuff test) at baseline | 6.6 ± 1.8 | 9.5 ± 4.0 |
| NO level after 12 | 7.8 ± 3.9 | 10.7 ± 4.5 |
| NO level (after cuff test) after 12 weeks | 7.0 ± 2.8 | 10.1 ± 5.2 |
Based on laboratory evaluation. Change in mean platelet aggregation after 12-week therapy versus baseline.
| percentage aggregation | Divaza | Placebo |
|---|---|---|
| ADP-PA at baseline | 46.9 ± 13.8 | 44.6 ± 14.1 |
| ADP-PA (after cuff test) at baseline | 45.0 ± 14.0 | 51.9 ± 15.7 |
| ADP-PA after 12 weeks | 45.3 ± 12.5 | 46.3 ± 9.4 |
| ADP-PA (after cuff test) after 12 weeks | 49.7 ± 14.6 | 52.5 ± 11.6 |
| ADR-PA at baseline | 48.4 ± 12.2 | 47.8 ± 16.4 |
| ADR-PA (after cuff test) at baseline | 44.7 ± 13.3 | 53.1 ± 16.8 |
| ADR-PA after 12 weeks | 47.7 ± 11.8 | 51.4 ± 11.3 |
| ADR-PA (after cuff test) after 12 weeks | 54.1 ± 8.6 | 57.4 ± 14.6 |
Collected over During the treatment period - 12 weeks (start after taking the first dose of the study drug, during the entire period of the study therapy and within 24 hours after the last dose of the study drug).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Divaza | 0/64 (0%) | 0/64 (0%) | 5/64 (7.8%) |
| Placebo | 0/59 (0%) | 0/59 (0%) | 3/59 (5.1%) |
| Event | Divaza | Placebo |
|---|---|---|
| Respiratory tract infectionInfections and infestations | 1/64 | 1/59 |
| Increased blood pressureInvestigations | 0/64 | 1/59 |
| NosebleedRespiratory, thoracic and mediastinal disorders | 0/64 | 1/59 |
| OdinophagyGastrointestinal disorders | 1/64 | 0/59 |
| NasopharyngitisInfections and infestations | 1/64 | 0/59 |
| HeadacheNervous system disorders | 1/64 | 0/59 |
| Arthropod biteInjury, poisoning and procedural complications | 1/64 | 0/59 |
| Age, Continuous(years) | Divaza | Placebo | Total |
|---|---|---|---|
| Mean | 61.4 ± 7.8 | 59.8 ± 7.4 | 60.7 ± 7.6 |
| Sex: Female, Male(Participants) | Divaza | Placebo | Total |
|---|---|---|---|
| Female | 51 | 40 | 91 |
| Male | 14 | 19 | 33 |
| Race and Ethnicity Not Collected(Participants) | Divaza | Placebo | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| Region of Enrollment(participants) | Divaza | Placebo | Total |
|---|---|---|---|
| Russia | 65 | 59 | 124 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Apr 2018 to primary completion in Apr 2019, 11 months.
Results were first posted in Aug 2021, 2 years 4 months after primary completion.
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