Prospecta in the Treatment of Cognitive, Behavioural and Psychiatric Disorders in Patients With Vascular Dementia.

Study Overview
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Brief Summary
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Study purpose: - evaluate safety and clinical efficacy of Prospecta in the treatment of cognitive, behavioural and psychiatric disorders in patients with vascular dementia. Study objectives: evaluate and compare changes in cognitive functions and in behavioural and psychiatric dementia symptoms in Prospecta and Placebo groups after 24-week therapy: evaluate and compare the frequency, severity and causal relationship of adverse events (AEs) with the type of therapy in Prospecta and Placebo groups (including central nervous system AEs during therapy, their relationship with the product and other characteristics).

Detailed Description
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Design: a multicenter double blind placebo-controlled parallel-group randomized clinical trial. The study will enroll male and female subjects aged 60-85 years diagnosed with vascular dementia (verified at Visit 1 and diagnosed according to the criteria of The National Institute of Neurological Disorders and Stroke National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences - NINDS-AIREN). Severity of vascular dementia should be moderate or mild (10-24 points according to Mini-Mental State Examination - MMSE), without signs of depression (total Cornell Scale for Depression in Dementia (CSDD) score ≤10). After signing patient information sheet (informed consent form), investigator will collect complaints and medical history, perform objective examination, record vital signs (blood pressure (BP), respiratory rate (RR), heart rate (HR)) and evaluate the compliance of the subject's diagnosis with NINDS-AIREN vascular criteria of dementia (Visit 1; from day -14 to day 1). The investigator will assess cognitive disorders using Mini-Mental State Examination (MMSE) and Montreal Сognitive Assessment (МоСА). The investigator will fill the Neuropsychiatric Inventory Сlinician (NPI-С), and СSDD scales. The subject will undergo brain MRI (unless brain MRI was held within the last 12 months prior to enrollment are available). Concomitant therapy and concurrent diseases and conditions will be recorded. If subject met inclusion criteria, he/she will be randomized to one of the two groups: group 1 will receive Prospecta 2 tablets twice daily; group 2 will receive Placebo using the study drug dosing regimen. Treatment duration will be 24 weeks during which 6 Visits will be made. At visits 2 and 3 (week 4±3 days and week 8±3 days) the investigator will make a phone call and collect the complaints, monitor the prescribed and concomitant therapy, evaluate therapeutic safety. At visit 4 (week 12±7 days) the investigator will collect complaints, record objective examination findings and vital signs, monitor the prescribed and concomitant therapy, evaluate therapeutic safety and compliance, issue the study product until the next visit. The investigator will fill MoCA and NPI-C. At visits 5 and 6 (week 16±3 days and week 20±3 days) the investigator will make a phone call and collect the complaints, monitor the prescribed and concomitant therapy, evaluate therapeutic safety. At visit 7 (week 24±7 days) the investigator will collect complaints, perform objective examination, record vital signs, monitor the prescribed and concomitant therapy, evaluate therapeutic safety, evaluate compliance. The investigator will fill MоСА and Clinical Global Impression Efficacy Index (CGI-EI). The investigator will fill NPI-C. During the study the treatment for underlying medical conditions will be allowed with the exception of the drugs indicated in the section Prohibited concomitant therapy.

Official Title
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Multicenter Double-blind Placebo-controlled Parallel-group Randomized Clinical Trial of Efficacy and Safety of Prospecta in the Treatment of Cognitive, Behavioural and Psychiatric Disorders in Patients With Vascular Dementia.

Conditions
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Vascular Dementia

Intervention / Treatment
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* Drug: Prospecta
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged 60-85 years old. Subjects with verified diagnosis of vascular dementia. Presence of all the vascular dementia criteria according to National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et l'Enshrinement en Neurosciences (NINDS-AIREN) criteria: Cognitive disorder syndrome: dysregulatory disorders: impaired aim formation, abstraction, initiation, planning, organization and maintenance of activities; memory disorders (may be moderate) consisting in impaired reproduction against relatively retained recognition and efficacy of cues. Presence of a cerebrovascular disease: according to brain imaging (expressed hypotensive irregular, spotty, foci located periventricularly and in deep segments of white matter or diffuse symmetrical low-density changes in semioval center projection combined with at least one lacunar focus; lack of nonlacunar cortical or cortical-subcortical infarctions and signs of cerebral damage of another etiology); focal symptoms in neurological status or their evidence in the history (hemiparesis, weakness of the lower part of facial muscles, Babinski's symptom, sensitivity disorders, dysarthria, gait disorders, extrapyramidal symptoms which may be explained by subcortical foci). Temporal relationship between dementia and cerebrovascular disorders (except for cases of subcortical vascular dementia): onset of dementia within 3-6 months post-stroke, sudden exacerbation of cognitive functions, step-wise progression of cognitive disorders. Availability of permanent caregiver throughout the study (nurse or relatives). Total Mini-Mental State Examination (MMSE) score - 10-24. Total MoCA score <26. Total NPI-C aggression and agitation domain score ≥14. Аbsence of depression (total Cornell Scale for Depression in Dementia (CSDD) score ≤10). Brain Magnetic Resonance Imaging (MRI) confirming the diagnosis of vascular dementia within 1 year prior to enrollment (or brain MRI performed at enrollment visit). Subjects giving their consent to use reliable contraception throughout the study (for males). Availability of signed patient information sheet and informed consent form for participation in the clinical trial. Exclusion Criteria: Signs of intracerebral hemorrhage, brain tumours causing dementia. Alzheimer's disease, Parkinson disease, Lewy body dementia, multiple system atrophy, Jacob-Creutzfeld disease, Pick syndrome, corticobasal degeneration. Injuries of head (S00-S09 International Statistical Classification of Diseases and Related Health Problems (ICD)-10) associated with impaired consciousness, cerebral contusion or open craniocerebral traumas. Toxicity-related dementia (including drug-induced), multiorgan failure or metabolic and toxic disorders (chronic hypothyroidism, decompensated diabetes mellitus, avitaminoses, etc.). Other psychiatric diseases besides dementia: mental disorders and behavioral disorders due to use of psychoactive substances (F10-19 ICD-10), schizophrenia, schizotypal and delusional disorders (F20-29 ICD-10). Mental retardation(F70-79 ICD-10). Inflammatory lesions of the brain with persistent neurological deficit. Malignant neoplasms. Previously diagnosed cardiovascular diseases with functional class III or IV (according to New York Heart Association, 1964). Unstable angina pectoris, myocardial infarction or ischemic stroke within the last 6 months. Female with childbearing potential. Allergy/intolerance of any of the study product components including secondary to lactase deficiency. Any conditions which will prevent from the subject's participation in the study, according to investigator's opinion. History of treatment noncompliance, mental diseases, alcoholism or drug abuse which will prevent from following the study procedures, according to investigator's opinion. Participation in clinical trials for 3 months prior to enrollment in this study. The patient is the study site employee directly involved in the study, or is an immediate family member of the investigator or has another conflict of interests. Spouses, parents, children, or siblings, regardless of whether they are siblings or adopted are considered immediate family members. The patient works at Materia Medica Holding, i.e. they are employees of the Company, temporary employees on a contract basis or appointed officials responsible for conduction of the study or their immediate family members.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double-blind placebo-controlled randomized
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prospecta<br>Two tablets per intake 2 times a day (approximately at the same time), outside of meal (between meals or 15 minutes prior to meal or drinking). The tablets should be held in mouth until completely dissolved. | Drug: Prospecta<br>* Oral administration.<br>* Other names: MMH-MAP;|
| Placebo Comparator: Placebo<br>Two tablets per intake 2 times a day (approximately at the same time), outside of meal (between meals or 15 minutes prior to meal or drinking). The tablets should be held in mouth until completely dissolved. | Drug: Placebo<br>* Oral administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean Montreal Сognitive Assessment (MoCA) score | Montreal Сognitive Assessment is used to evaluate changes in cognitive function. It assesses multiple cognitive domains: attention, concentration, executive functions, memory, language, visuospatial skills, abstraction, calculation and orientation. Maximum score is 30; score ≥ 26 is considered to be normal. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean NPI-С score | Neuropsychiatric Inventory-Clinician (NPI-C) allows to evaluate severity of behavioural and mental disorders associated with dementia. The scale consists of 14 domains evaluating frequency and severity of delusional ideas, hallucinations, agitation, aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor behaviour, sleep and appetite disorders, aberrant vocalizations. Scoring for delusional ideas (8 items) is 0-24 points, for hallucinations (7 items) - 0-21, agitation (13 items) - 0-39, aggression (8 items) - 0-24, dysphoria (13 items) - 0-39, anxiety (14 items) - 0-42, euphoria (6 items) - 0-18, apathy (11 items) - 0-33, disinhibition (16 items) - 0-48, irritability (12 items) - 0-36 , aberrant motor behaviour (9 items) - 0-27, sleep disorders (8 items) - 0-24, appetite disorders (9 items) - 0-27, aberrant vocalizations (8 items) - 0-24. Total maximum score for all domains is 426. | 24 weeks | 
| Change in mean Montreal Сognitive Assessment (MoCA) score | Montreal Сognitive Assessment is used to evaluate changes in cognitive function. It assesses multiple cognitive domains: attention, concentration, executive functions, memory, language, visuospatial skills, abstraction, calculation and orientation. Maximum score is 30; score ≥ 26 is considered to be normal. | 12 weeks | 
| Change in mean Neuropsychiatric Inventory-Clinician (NPI-С) score | Neuropsychiatric Inventory-Clinician (NPI-C) allows to evaluate severity of behavioural and mental disorders associated with dementia. The scale consists of 14 domains evaluating frequency and severity of delusional ideas, hallucinations, agitation, aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor behaviour, sleep and appetite disorders, aberrant vocalizations. Scoring for delusional ideas (8 items) is 0-24 points, for hallucinations (7 items) - 0-21, agitation (13 items) - 0-39, aggression (8 items) - 0-24, dysphoria (13 items) - 0-39, anxiety (14 items) - 0-42, euphoria (6 items) - 0-18, apathy (11 items) - 0-33, disinhibition (16 items) - 0-48, irritability (12 items) - 0-36 , aberrant motor behaviour (9 items) - 0-27, sleep disorders (8 items) - 0-24, appetite disorders (9 items) - 0-27, aberrant vocalizations (8 items) - 0-24. Total maximum score for all domains is 426. | 12 weeks | 
| Mean Clinical Global Impression Efficacy Index (СGI-EI) score | Clinical Global Impression Efficacy Index (CGI-EI). TheCGI-E is a 4×4 rating scale that assesses the therapeutic effect of treatment with psychiatric medication and associated side effects. | 24 weeks |