Chronic Cerebral Ischemia
Conditions
Brief summary
An open-label, prospective, observational, multicenter study. The study enrolls adult outpatients with CCI from 8 federal districts of the Russian Federation.
Detailed description
Medical data (demographic and clinical characteristics - diagnosis, MoCA test results) are collected from patients to whom Divaza is prescribed to be taken according to the following regimen: 2 tablets 3 times per day for 12 weeks. Neurologists assess the patients' cognitive functions with MoCA scale before starting therapy with Divaza (visit 1) and 12 weeks after the treatment (visit 2). The efficacy of Divaza for the treatment of cognitive impairment in patients with chronic cerebral ischemia (CCI) is evaluated. Safety is assessed based on the frequency and severity of adverse events. In addition, the relationship between MoCA test performance and gender or regional social and economic factors is evaluated.
Interventions
DRUGDivaza
Oral administration.
Sponsors
Materia Medica Holding
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Patients of either gender aged 18+ years. 2. Diagnosis of chronic cerebral ischemia (CCI) based on the clinical history of underlying vascular disease(atherosclerosis and/or arterial hypertension) and neurological signs. 3. Unchanged basic therapy of CCI and underlying vascular disease for a previous 3 month. 4. Signed informed consent form.
Exclusion criteria
1. Other neurological diseases. 2. Any known allergy to/intolerance of any constituent of the medication. 3. Pregnancy, breast-feeding. 4. Participation in other clinical trials for 3 months prior to enrollment in this study. 5. The patient is related to the research personnel of the investigative sites that are directly involved in the study, or is the immediate relative of the investigator, or the employee of OOO NPF Materia Medica Holding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean MoCA Score at Week 1 and the End of the 12-week Therapy | week 1 to 12 week | MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome).MoCA test allows to evaluate the presence of cognitive impairment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients With a MoCA Score ≤ 17 at the End of the 12-week Therapy | week1 to week 12 | The number of patients with dementia. MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome) |
| The Dynamics of Mean MoCA Score in Each Age Group | week1 to week 12 | Age groups:young \<35 yo, middle-aged - 35-59 yo, elderly - 60-75 yo, senile - 75-90 yo MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome) |
| The Number of Patients With a MoCA Score <26 at 12 Week | 12 week | The number of patients with mild cognitive impairment. MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome) |
| The Number of Patients With a MoCA Score Improvement (Increase in Scores) in Age Groups | week1 to week 12 | Age groups:young \<35 yo, middle-aged - 35-59 yo, elderly - 60-75 yo, senile - 75-90 yo MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome) |
Other
| Measure | Time frame | Description |
|---|---|---|
| The Relationship Between Cognitive Impairment and Patients' Gender | Data measured at baseline | Evaluation of the relationship between baseline MoCA test results and gender. MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome) |
| The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Data measured at baseline | Evaluation of the relationship between baseline MoCA test results and regional developmental social or economic indicators (poverty, infant mortality, migration, life expectancy, innovation rate, professional development, number of university students, number of R&D personnel, resources spent on R&D, number of doctors, number of hospitals and outpatient clinics, hospital capacity, fertility rate, quality of life index,income). Relevance of factors (unitless value) provided. The higher the more influential the factor is. Relevance was assessed with Boruta approach: KURSA, Miron B.; RUDNICKI, Witold R.. Feature Selection with the Boruta Package. Journal of Statistical Software, \[S.l.\], v. 36, Issue 11, p. 1 - 13, sep. 2010. ISSN 1548-7660. Available at: \<http://www.jstatsoft.org/v036/i11\>. Date accessed: 24 nov. 2020. doi:http://dx.doi.org/10.18637/jss.v036.i11. |
Participant flow
Recruitment details
Recruitment period: October 2016 January 2017 Location: outpatient clinics from 8 federal districts of the Russian Federation
Participants by arm
| Arm | Count |
|---|---|
| Divaza Treatment Group All participants received Divaza treatment | 1,876 |
| Total | 1,876 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Protocol Violation | 9 |
| Overall Study | Withdrawal by Subject | 695 |
Baseline characteristics
| Characteristic | Divaza Treatment Group |
|---|---|
| Age, Continuous | 65.7 years STANDARD_DEVIATION 19.1 |
| Age, Customized Elderly (60-75 yo) | 1062 participants |
| Age, Customized Middle aged (35-59 yo) | 501 participants |
| Age, Customized Senile (75-90 yo) | 265 participants |
| Age, Customized Young (<35 yo) | 25 participants |
| Baseline MoCA score | 19.4 units on a scale STANDARD_DEVIATION 5.1 |
| Sex: Female, Male Female | 1139 Participants |
| Sex: Female, Male Male | 708 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2,583 |
| other Total, other adverse events | 17 / 2,583 |
| serious Total, serious adverse events | 0 / 2,583 |
Outcome results
Primary
Mean MoCA Score at Week 1 and the End of the 12-week Therapy
MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome).MoCA test allows to evaluate the presence of cognitive impairment
Time frame: week 1 to 12 week
Population: MoCA scores were not reported in 21 patients at least at one timepoint (excluded from analysis)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Divaza Treatment Group | Mean MoCA Score at Week 1 and the End of the 12-week Therapy | 1 week | 19.42 score on a scale | Standard Deviation 5.13 |
| Divaza Treatment Group | Mean MoCA Score at Week 1 and the End of the 12-week Therapy | 12 week | 24 score on a scale | Standard Deviation 4.6 |
p-value: <0.0000195% CI: [4.42, 4.72]t-test, 2 sided
Secondary
The Dynamics of Mean MoCA Score in Each Age Group
Age groups:young \<35 yo, middle-aged - 35-59 yo, elderly - 60-75 yo, senile - 75-90 yo MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome)
Time frame: week1 to week 12
Population: Patients who did not reported age or both MoCA scores were excluded from analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Divaza Treatment Group | The Dynamics of Mean MoCA Score in Each Age Group | week 1 | 24 score on a scale | Standard Deviation 5.6 |
| Divaza Treatment Group | The Dynamics of Mean MoCA Score in Each Age Group | week 12 | 26.4 score on a scale | Standard Deviation 5.6 |
| Middle-aged Patients 35-59 yo | The Dynamics of Mean MoCA Score in Each Age Group | week 12 | 25.7 score on a scale | Standard Deviation 3.6 |
| Middle-aged Patients 35-59 yo | The Dynamics of Mean MoCA Score in Each Age Group | week 1 | 20.94 score on a scale | Standard Deviation 4.93 |
| Elderly Patients 60-75 yo | The Dynamics of Mean MoCA Score in Each Age Group | week 1 | 19.39 score on a scale | Standard Deviation 4.7 |
| Elderly Patients 60-75 yo | The Dynamics of Mean MoCA Score in Each Age Group | week 12 | 23.9 score on a scale | Standard Deviation 4.2 |
| Senile Patients 75-90 yo | The Dynamics of Mean MoCA Score in Each Age Group | week 1 | 16.23 score on a scale | Standard Deviation 5.42 |
| Senile Patients 75-90 yo | The Dynamics of Mean MoCA Score in Each Age Group | week 12 | 20.7 score on a scale | Standard Deviation 5.6 |
Comparison: Change of mean MoCA scorep-value: <0.0795% CI: [-0.21, 4.96]ANOVA
Comparison: Change of mean MoCA scorep-value: <0.0195% CI: [4.17, 5.31]ANOVA
Comparison: Change of mean MoCA scorep-value: <0.0195% CI: [4.16, 4.94]ANOVA
Comparison: Change of mean MoCA scorep-value: <0.0195% CI: [3.7, 5.27]ANOVA
Secondary
The Number of Patients With a MoCA Score ≤ 17 at the End of the 12-week Therapy
The number of patients with dementia. MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome)
Time frame: week1 to week 12
Population: MoCA scores were not reported in 21 patients at least at one timepoint (excluded from analysis)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Divaza Treatment Group | The Number of Patients With a MoCA Score ≤ 17 at the End of the 12-week Therapy | week 1 | 489 participants |
| Divaza Treatment Group | The Number of Patients With a MoCA Score ≤ 17 at the End of the 12-week Therapy | week 12 | 117 participants |
Comparison: Odds ratio of occuring MoCA score \<17 was assessedp-value: <0.0000195% CI: [4.28, 6.64]Fisher Exact
Secondary
The Number of Patients With a MoCA Score <26 at 12 Week
The number of patients with mild cognitive impairment. MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome)
Time frame: 12 week
Population: MoCA scores were not reported in 21 patients at least at one timepoint (excluded from analysis)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Divaza Treatment Group | The Number of Patients With a MoCA Score <26 at 12 Week | week 1 | 1676 participants |
| Divaza Treatment Group | The Number of Patients With a MoCA Score <26 at 12 Week | week 12 | 1048 participants |
Comparison: Odds ratio of occuring MoCA score \<26 was assessedp-value: <0.0000195% CI: [6.01, 8.67]Fisher Exact
Secondary
The Number of Patients With a MoCA Score Improvement (Increase in Scores) in Age Groups
Age groups:young \<35 yo, middle-aged - 35-59 yo, elderly - 60-75 yo, senile - 75-90 yo MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome)
Time frame: week1 to week 12
Population: Patients who did not reported age or both MoCA scores were excluded from analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Divaza Treatment Group | The Number of Patients With a MoCA Score Improvement (Increase in Scores) in Age Groups | 5 participants |
| Middle-aged Patients 35-59 yo | The Number of Patients With a MoCA Score Improvement (Increase in Scores) in Age Groups | 199 participants |
| Elderly Patients 60-75 yo | The Number of Patients With a MoCA Score Improvement (Increase in Scores) in Age Groups | 616 participants |
| Senile Patients 75-90 yo | The Number of Patients With a MoCA Score Improvement (Increase in Scores) in Age Groups | 214 participants |
Other Pre-specified
The Relationship Between Cognitive Impairment and Patients' Gender
Evaluation of the relationship between baseline MoCA test results and gender. MoCA - Montreal Cognitive Assessment (0-30 scores, higher scores mean a better outcome)
Time frame: Data measured at baseline
Population: Patients who did not reported sex or baseline MoCA score were excluded from analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Patients' Gender | 19.7 units on a scale | Standard Deviation 5.09 |
| Middle-aged Patients 35-59 yo | The Relationship Between Cognitive Impairment and Patients' Gender | 18.9 units on a scale | Standard Deviation 5.13 |
p-value: 0.001195% CI: [0.321, 1.28]ANOVA
Other Pre-specified
The Relationship Between Cognitive Impairment and Regional Social/Economic Factors
Evaluation of the relationship between baseline MoCA test results and regional developmental social or economic indicators (poverty, infant mortality, migration, life expectancy, innovation rate, professional development, number of university students, number of R&D personnel, resources spent on R&D, number of doctors, number of hospitals and outpatient clinics, hospital capacity, fertility rate, quality of life index,income). Relevance of factors (unitless value) provided. The higher the more influential the factor is. Relevance was assessed with Boruta approach: KURSA, Miron B.; RUDNICKI, Witold R.. Feature Selection with the Boruta Package. Journal of Statistical Software, \[S.l.\], v. 36, Issue 11, p. 1 - 13, sep. 2010. ISSN 1548-7660. Available at: \<http://www.jstatsoft.org/v036/i11\>. Date accessed: 24 nov. 2020. doi:http://dx.doi.org/10.18637/jss.v036.i11.
Time frame: Data measured at baseline
Population: Incomplete data (with respect to used variables) was excluded
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Professional development index | 6.13 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Nursing personnel | 4.69 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | shadowMax (reference zero-importance feature) | 2.66 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Age | 39.85 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Poverty percentage | 8.36 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Infant mortality | 7.97 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Migration index | 7.92 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Life expectancy | 6.42 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Number of R&D personnel | 5.81 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Hospitals number | 5.65 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | R&D expenditures | 5.6 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Innovation rate | 5.56 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Hospitals capacity | 4.89 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Fertility rate | 4.87 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | QoL index | 4.85 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Outpatient clinics | 4.73 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Income level | 3.83 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | University students | 3.79 unitless feature importance |
| Divaza Treatment Group | The Relationship Between Cognitive Impairment and Regional Social/Economic Factors | Number of doctors | 3.78 unitless feature importance |