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

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.

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).

Study Overview

• Status: Completed
• Conditions: Vascular Dementia
• Intervention / Treatment: Drug: Placebo; Drug: Prospecta

Detailed Description

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".

• Study Type: Interventional
• Enrollment (Actual): 406
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Arkhangelsk, Russian Federation, 163000
    • Northern State Medical University/Department of Family Medicine and Internal Medicine
  • Belgorod, Russian Federation, 308007
    • Belgorod Regional Clinical Hospital of St. Joasaph/Neurological department
  • Bryansk, Russian Federation, 241004
    • Hospital "Russian Railways - Medicine" of the city of Bryansk/Medical rehabilitation department
  • Ekaterinburg, Russian Federation, 6620030
    • Sverdlovsk Regional Clinical Psychiatric Hospital
  • Engels, Russian Federation, 413124
    • Engels psychiatric hospital
  • Kazan, Russian Federation, 420012
    • Kazan State Medical University/Department of Neurology and Rehabilitation
  • Moscow, Russian Federation, 115516
    • City Clinical Hospital named after V.M. Buyanov of the Moscow City Health Department/1st neurological department
  • Moscow, Russian Federation, 117198
    • Peoples' Friendship University of Russia/Department of Psychiatry, Psychotherapy and Psychosomatic Pathology
  • Moscow, Russian Federation, 117593
    • Central Clinical Hospital of the Russian Academy of Sciences/Treatment and Diagnostic Center
  • Nikol'skoye, Russian Federation, 188357
    • Psychiatric hospital # 1 named after P.P. Kashchenko
  • Nizhny Novgorod, Russian Federation, 603005
    • Privolzhsky Research Medical University/Department of Medical Rehabilitation
  • Nizhny Novgorod, Russian Federation, 603126
    • Nizhny Novgorod Regional Clinical Hospital. N. A. Semashko/Outpatient department
  • Orenburg, Russian Federation, 460006
    • Orenburg Regional Clinical Psychiatric Hospital # 1/Psychoneurological dispensary
  • Pyatigorsk, Russian Federation, 357538
    • Pyatigorsk City Clinical Hospital # 2/Neurological department
  • Rostov-on-Don, Russian Federation, 344000
    • LLC "Treatment and reabilitation research center " PHOENIX "/Day hospital # 1
  • Saint Petersburg, Russian Federation, 190121
    • Psychoneurological dispensary # 10/Medical rehabilitation department
  • Saint Petersburg, Russian Federation, 190121
    • St. Nicholas Psychiatric Hospital
  • Saint Petersburg, Russian Federation, 192242
    • St. Petersburg Research Institute of Emergency Medicine named after I.I. Janelidze/Medical Rehabilitation Department
  • Saint Petersburg, Russian Federation, 195176
    • Psychoneurological dispensary # 5/Day hospital
  • Saint-Petersburg, Russian Federation, 194291
    • Leningrad Regional Clinical Hospital/Neurological department
  • Samara, Russian Federation, 443096
    • Samara City Clinical Hospital # 1 named after N.I. Pirogov/Neurological department for patients with cerebrovascular accident # 24
  • Saratov, Russian Federation, 410012
    • Saratov State Medical University V. I. Razumovsky/Department of Neurology named after K.N. Tretyakov
  • Saratov, Russian Federation, 410028
    • City Clinical Hospital # 2 named after V.I. Razumovsky
  • Saratov, Russian Federation, 410038
    • Saratov City Psychoneurological Dispensary
  • Saratov, Russian Federation, 410060
    • Regional Clinical Psychiatric Hospital of St. Sophia
  • Smolensk, Russian Federation, 214018
    • Smolensk Regional Clinical Hospital
  • Stavropol, Russian Federation, 355038
    • Stavropol Regional Clinical Specialized Psychiatric Hospital # 1/Somatogeriatric department #19
  • Ufa, Russian Federation, 450005
    • Republican clinical hospital named after G.G. Kuvatov
  • Ufa, Russian Federation, 450008
    • Bashkir State Medical University/Department of Neurology
  • Ulyanovsk, Russian Federation, 432063
    • Ulyanovsk Regional Clinical Hospital/Outpatient department
  • Vladimir, Russian Federation, 600023
    • Regional Clinic Hospital
  • Volgograd, Russian Federation, 400131
    • Volgograd State Medical University/Department of Neurology, Neurosurgery with the Course of Medical Genetics
  • Vsevolozhsk, Russian Federation, 188643
    • Vsevolozhsk clinical interdistrict hospital/Neurological department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects aged 60-85 years old.
2. Subjects with verified diagnosis of vascular dementia.

3. 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:

   1. 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.

   2. 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).
   3. 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.
4. Availability of permanent caregiver throughout the study (nurse or relatives).
5. Total Mini-Mental State Examination (MMSE) score - 10-24.
6. Total MoCA score <26.
7. Total NPI-C aggression and agitation domain score ≥14.
8. Аbsence of depression (total Cornell Scale for Depression in Dementia (CSDD) score ≤10).
9. Brain Magnetic Resonance Imaging (MRI) confirming the diagnosis of vascular dementia within 1 year prior to enrollment (or brain MRI performed at enrollment visit).
10. Subjects giving their consent to use reliable contraception throughout the study (for males).
11. Availability of signed patient information sheet and informed consent form for participation in the clinical trial.

Exclusion Criteria:

1. Signs of intracerebral hemorrhage, brain tumours causing dementia.
2. Alzheimer's disease, Parkinson disease, Lewy body dementia, multiple system atrophy, Jacob-Creutzfeld disease, Pick syndrome, corticobasal degeneration.
3. 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.
4. Toxicity-related dementia (including drug-induced), multiorgan failure or metabolic and toxic disorders (chronic hypothyroidism, decompensated diabetes mellitus, avitaminoses, etc.).
5. 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).
6. Mental retardation(F70-79 ICD-10).
7. Inflammatory lesions of the brain with persistent neurological deficit.
8. Malignant neoplasms.
9. Previously diagnosed cardiovascular diseases with functional class III or IV (according to New York Heart Association, 1964).
10. Unstable angina pectoris, myocardial infarction or ischemic stroke within the last 6 months.
11. Female with childbearing potential.
12. Allergy/intolerance of any of the study product components including secondary to lactase deficiency.
13. Any conditions which will prevent from the subject's participation in the study, according to investigator's opinion.
14. History of treatment noncompliance, mental diseases, alcoholism or drug abuse which will prevent from following the study procedures, according to investigator's opinion.
15. Participation in clinical trials for 3 months prior to enrollment in this study.
16. 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.
17. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prospecta; 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; Oral administration.; Other Names: MMH-MAP
Placebo Comparator: Placebo; 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; Oral administration.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Materia Medica Holding
• Investigators: Principal Investigator: Pavel Kamchatnov, professor, V.M. Buyanov Moscow City Clinical Hospital, Moscow, Russia

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2020
• Primary Completion (Actual): September 22, 2022
• Study Completion (Actual): September 22, 2022

Study Registration Dates

• First Submitted: September 10, 2020
• First Submitted That Met QC Criteria: September 10, 2020
• First Posted (Actual): September 17, 2020

Study Record Updates

• Last Update Posted (Actual): January 23, 2023
• Last Update Submitted That Met QC Criteria: January 20, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Neurocognitive Disorders; Intracranial Arterial Diseases; Intracranial Arteriosclerosis; Leukoencephalopathies; Problem Behavior; Mental Disorders; Dementia; Dementia, Vascular
• Other Study ID Numbers: MMH-MAP-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No