Prospekta in the Treatment of Cognitive, Behavioral and Psychiatric Disorders in Patients With Vascular Dementia.

Phase 3

Completed

• Conditions: Vascular Dementia
• Interventions: Drug: Prospekta; Drug: Placebo

• Registration Number: NCT04552041
• Lead Sponsor: Materia Medica Holding

Brief Summary

Study purpose:

- evaluate clinical efficacy ands afety of Prospekta in the treatment of cognitive, behavioral and psychiatric disorders in patients with vascular dementia.

Study objectives:

* evaluate and compare changes in cognitive functions, in behavioral and in psychiatric dementia symptoms in Prospekta and Placebo groups after 24-weeks of treatment

* evaluate and compare the frequency, severity and causal relationship of adverse events (AEs) with the type of therapy in Prospekta and Placebo groups (including central nervous system AEs during therapy, their relationship with the study drug and other characteristics).

Detailed Description

Design: double-blind placebo-controlled randomized parallel-group clinical trial. The study will enroll male and female patients aged 60-85 years inclusively diagnosed with vascular dementia verified at Visit 1 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) to participate in the study, at Visit 1 (from day -14 to day 1) complaints and medical history will be collected, objective examination, recording vital signs (BP, RR, HR) will be performed and compliance of the subject's diagnosis with NINDS-AIREN vascular dementia criteria will be evaluated. The study investigator will assess cognitive disorders using Mini-Mental State Examination (MMSE) and Montreal Сognitive Assessment (МоСА). The investigator and the patient's caregiver will fill Neuropsychiatric Inventory Сlinician (NPI-С), and СSDD scales. The patient will undergo brain MRI (in the absence of brain MRI data within the previous 12 months before inclusion in the study).

Concomitant therapy and concomitant diseases and conditions will be recorded. If inclusion/exclusion criteria are met, the patient will be randomized to one of the two groups: group 1 will receive Prospekta 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 study 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 study investigator will collect complaints, record objective examination findings and vital signs, monitor the prescribed and concomitant therapy, evaluate therapeutic safety and compliance, dispense the study drug until the next visit. The study investigator and caregiver will fill NPI-C.

At visits 5 and 6 (week 16±3 days and week 20±3 days) the study 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 study investigator will collect complaints, perform objective examination, record vital signs, monitor the prescribed and concomitant therapy, evaluate therapeutic safety, evaluate compliance. The study investigator will fill MоСА and Clinical Global Impression Efficacy Index (CGI-EI). The study investigator and caregiver will fill NPI-C.

During the study the treatment for concomitant diseases will be allowed with the exception of the drugs specified in the section "Prohibited concomitant therapy".

Study Timeline

• Study First Submitted: 2020-09-10
• Study First Submitted QC: 2020-09-10
• Study First Posted: 2020-09-17
• Study Start: 2020-12-03
• Primary Completion: 2022-09-22
• Study Completion: 2022-09-22
• Status Verified: 2023-01
• Results First Submitted: 2024-01-11
• Results First Submitted QC: 2024-08-08
• Last Update Submitted: 2024-08-08
• Results First Posted: 2024-10-28
• Last Update Posted: 2024-10-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 406

Inclusion Criteria

1. Subjects aged 60-85 years old inclusively.

2. Subjects with verified diagnosis of vascular dementia.

3. Presence of all the vascular dementia criteria according to NINDS-AIREN:

   A. Presence of dementia, which is defined as a decline in cognitive function relative to the previous level of functioning, manifested by impairments in memory and two or more cognitive domains (orientation, attention, language, visuospatial functions, executive functions, motor control and praxis), preferably established during a clinical trial and confirmed by neuropsychological testing.

   The cognitive impairment must be so severe that it affects daily activity, reducing it independently of the physical consequences of the stroke.

   B. The presence of cerebrovascular disease, confirmed by signs of focal damage on neurological examination, such as hemiparesis, lower facial weakness, Babinski sign, sensory deficit, hemianopsia or dysarthria associated with stroke (either a history of stroke or absence of such anamnestic information), and neuroimaging (CT or MRI) signs of cerebrovascular disease, including multiple infarcts in the territory of large vessels, or a single infarction in a strategically important area (angular gyrus, thalamus, basal ganglia, or the territory of the anterior or posterior cerebral arteries), as well as multiple lacunae in the region of the basal ganglia or white matter, or significant damage to the periventricular white matter, or a combination of the above lesions.

   C. There is an association between dementia and cerebrovascular disease as follows:

   1. onset of dementia within 3 months of stroke;
   2. sharp deterioration of cognitive functions; or fluctuating, stepwise progression of cognitive impairment.

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 MRI confirming the diagnosis of vascular dementia within 1 year prior to enrollment (or brain MRI performed at enrollment visit).

10. Patients 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) 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) schizophrenia, schizotypal and delusional disorders (F20-29).
6. Mental retardation (F70-79).
7. Inflammatory lesions of the brain with persistent neurological deficit.
8. Malignant neoplasms.
9. Previously diagnosed cardiovascular diseases with functional class IV (according to New York Heart Association, 1964).
10. Unstable angina pectoris, myocardial infarction or ischemic stroke within the last 6 months.
11. Female patients with childbearing potency.
12. Allergy/intolerance of any of the study drugs components including secondary to lactase deficiency.
13. Any conditions which, according to the investigator opinion, may interfere with the patient's participation in the study.
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. Use of any medications specified in "Prohibited concomitant medications" within 1 month before enrollment.
17. Patients who are related to any of the on-site research personnel directly involved in the conduct of the trial or are an immediate relative of the study investigator. 'Immediate relative' means husband, wife, parent, son, daughter, brother, or sister (regardless of whether they are natural or adopted).
18. Patients who work for OOO "NPF "Materia Medica Holding" (i.e. the company's employees, temporary contract workers, designated officials responsible for carrying out the research or any immediate relatives of the aforementioned).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prospekta	Prospekta	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. The overall duration of treatment is 24 weeks.
Placebo	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. The overall duration of treatment is 24 weeks.

Primary Outcome Measures

Name	Time	Method
Change in Mean Montreal Сognitive Assessment (MoCA) Score	Baseline, 24 weeks	MoCA is the test for assessment of cognitive impairment. The score ranges between 0 and 30. A score of 26-30 is normal. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.

Secondary Outcome Measures

Name	Time	Method
Change in Mean Neuropsychiatric Inventory-Clinician (NPI-С) Score	Baseline, 12 weeks	NPI-C allows to evaluate severity of behavioural and mental disorders associated with dementia. The scale consists of 14 domains. 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. Each item is rated for frequency (a 4-point scale from 1 \[occasionally\] to 4 \[very frequent\]) and severity (a 3-point scale from 1 \[mild\] to 3 \[marked\]). The total NPI score is the frequency ratings multiplied by the severity ratings. Total maximum score for all domains is 426 (higher score indicates worse outcome).
Change in Mean Montreal Сognitive Assessment (MoCA) Score	Baseline, 12 weeks	MoCA is the test for assessment of cognitive impairment. The score ranges between 0 and 30. A score of 26-30 is normal. A score less than 26 is considered as mild cognitive impairment. Higher values represent a better outcome.
Mean Clinical Global Impression Efficacy Index (СGI-EI) Score	After 24 weeks of the treatment.	Indicators of therapeutic and side effects, efficacy index on the scale of the general clinical impression CGI-EI (Clinical Global Impression Scale - Efficacy Index) after 24 weeks from the start of study therapy. Evaluation of the response to treatment should take into account both therapeutic efficacy and treatment-related side effects. Side effects value from 1 to 4. Therapeutic effect value as 0,4,8 or 12 points. The efficacy index is a sum. The minimum value is 1, the maximum value is 16. A lower score on the scales is the best outcome.

Trial Locations

Locations (33)

Northern State Medical University/Department of Family Medicine and Internal Medicine; 🇷🇺 Arkhangelsk, Russian Federation

Belgorod Regional Clinical Hospital of St. Joasaph/Neurological department; 🇷🇺 Belgorod, Russian Federation

Psychiatric hospital # 1 named after P.P. Kashchenko; 🇷🇺 Nikol'skoye, Russian Federation

Nizhny Novgorod Regional Clinical Hospital. N. A. Semashko/Outpatient department; 🇷🇺 Nizhny Novgorod, Russian Federation

Orenburg Regional Clinical Psychiatric Hospital # 1/Psychoneurological dispensary; 🇷🇺 Orenburg, Russian Federation

Pyatigorsk City Clinical Hospital # 2/Neurological department; 🇷🇺 Pyatigorsk, Russian Federation

LLC "Treatment and reabilitation research center " PHOENIX "/Day hospital # 1; 🇷🇺 Rostov-on-Don, Russian Federation

Ulyanovsk Regional Clinical Hospital/Outpatient department; 🇷🇺 Ulyanovsk, Russian Federation

Engels Psychiatric Hospital; 🇷🇺 Engels, Russian Federation

Saratov State Medical University V. I. Razumovsky/Department of Neurology named after K.N. Tretyakov; 🇷🇺 Saratov, Russian Federation

Regional Clinical Psychiatric Hospital of St. Sophia; 🇷🇺 Saratov, Russian Federation

Central Clinical Hospital of the Russian Academy of Sciences/Treatment and Diagnostic Center; 🇷🇺 Moscow, Russian Federation

St. Nicholas Psychiatric Hospital; 🇷🇺 Saint Petersburg, Russian Federation

Psychoneurological dispensary # 5/Day hospital; 🇷🇺 Saint Petersburg, Russian Federation

Peoples' Friendship University of Russia/Department of Psychiatry, Psychotherapy and Psychosomatic Pathology; 🇷🇺 Moscow, Russian Federation

Regional Clinic Hospital; 🇷🇺 Vladimir, Russian Federation

Volgograd State Medical University/Department of Neurology, Neurosurgery with the Course of Medical Genetics; 🇷🇺 Volgograd, Russian Federation

Leningrad Regional Clinical Hospital/Neurological department; 🇷🇺 Saint-Petersburg, Russian Federation

Hospital "Russian Railways - Medicine" of the city of Bryansk/Medical rehabilitation department; 🇷🇺 Bryansk, Russian Federation

Sverdlovsk Regional Clinical Psychiatric Hospital; 🇷🇺 Ekaterinburg, Russian Federation

City Clinical Hospital named after V.M. Buyanov of the Moscow City Health Department/1st neurological department; 🇷🇺 Moscow, Russian Federation

Kazan State Medical University/Department of Neurology and Rehabilitation; 🇷🇺 Kazan, Russian Federation

Privolzhsky Research Medical University/Department of Medical Rehabilitation; 🇷🇺 Nizhny Novgorod, Russian Federation

Samara City Clinical Hospital # 1 named after N.I. Pirogov/Neurological department for patients with cerebrovascular accident # 24; 🇷🇺 Samara, Russian Federation

City Clinical Hospital # 2 named after V.I. Razumovsky; 🇷🇺 Saratov, Russian Federation

Psychoneurological dispensary # 10/Medical rehabilitation department; 🇷🇺 Saint Petersburg, Russian Federation

St. Petersburg Research Institute of Emergency Medicine named after I.I. Janelidze/Medical Rehabilitation Department; 🇷🇺 Saint Petersburg, Russian Federation

Saratov City Psychoneurological Dispensary; 🇷🇺 Saratov, Russian Federation

Smolensk Regional Clinical Hospital; 🇷🇺 Smolensk, Russian Federation

Vsevolozhsk clinical interdistrict hospital/Neurological department; 🇷🇺 Vsevolozhsk, Russian Federation

Republican Clinical Hospital named after G.G. Kuvatov; 🇷🇺 Ufa, Russian Federation

Bashkir State Medical University/Department of Neurology; 🇷🇺 Ufa, Russian Federation

Stavropol Regional Clinical Specialized Psychiatric Hospital # 1/Somatogeriatric department #19; 🇷🇺 Stavropol, Russian Federation