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

Vascular Dementia Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04552041
• Other study ID #: MMH-MAP-003
• Status: Completed
• Phase: Phase 3
• Start date: December 3, 2020
• Est. completion date: September 22, 2022

Study information

• Verified date: January 2023
• Source: Materia Medica Holding
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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".

Recruitment information / eligibility

• Status: Completed
• Enrollment: 406
• Est. completion date: September 22, 2022
• Est. primary completion date: September 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 85 Years

Eligibility

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. ?bsence 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.

Related Conditions & MeSH terms

• Dementia
• Dementia, Vascular
• Mental Disorders
• Problem Behavior
• Vascular Dementia

Intervention

Drug:
• Prospecta
Oral administration.
• Placebo
Oral administration.

Locations

Country	Name	City	State
Russian Federation	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	Hospital "Russian Railways - Medicine" of the city of Bryansk/Medical rehabilitation department	Bryansk
Russian Federation	Sverdlovsk Regional Clinical Psychiatric Hospital	Ekaterinburg
Russian Federation	Engels Psychiatric Hospital	Engels
Russian Federation	Kazan State Medical University/Department of Neurology and Rehabilitation	Kazan
Russian Federation	Central Clinical Hospital of the Russian Academy of Sciences/Treatment and Diagnostic Center	Moscow
Russian Federation	City Clinical Hospital named after V.M. Buyanov of the Moscow City Health Department/1st neurological department	Moscow
Russian Federation	Peoples' Friendship University of Russia/Department of Psychiatry, Psychotherapy and Psychosomatic Pathology	Moscow
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	Privolzhsky Research Medical University/Department of Medical Rehabilitation	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	Psychoneurological dispensary # 10/Medical rehabilitation department	Saint Petersburg
Russian Federation	Psychoneurological dispensary # 5/Day hospital	Saint Petersburg
Russian Federation	St. Nicholas Psychiatric Hospital	Saint Petersburg
Russian Federation	St. Petersburg Research Institute of Emergency Medicine named after I.I. Janelidze/Medical Rehabilitation Department	Saint Petersburg
Russian Federation	Leningrad Regional Clinical Hospital/Neurological department	Saint-Petersburg
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	Regional Clinical Psychiatric Hospital of St. Sophia	Saratov
Russian Federation	Saratov City Psychoneurological Dispensary	Saratov
Russian Federation	Saratov State Medical University V. I. Razumovsky/Department of Neurology named after K.N. Tretyakov	Saratov
Russian Federation	Smolensk Regional Clinical Hospital	Smolensk
Russian Federation	Stavropol Regional Clinical Specialized Psychiatric Hospital # 1/Somatogeriatric department #19	Stavropol
Russian Federation	Bashkir State Medical University/Department of Neurology	Ufa
Russian Federation	Republican Clinical Hospital named after G.G. Kuvatov	Ufa
Russian Federation	Ulyanovsk Regional Clinical Hospital/Outpatient department	Ulyanovsk
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	Vsevolozhsk clinical interdistrict hospital/Neurological department	Vsevolozhsk

Sponsors (1)

Lead Sponsor	Collaborator
Materia Medica Holding

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in mean Montreal ?ognitive Assessment (MoCA) score	Montreal ?ognitive 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	Change in mean NPI-? 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
Secondary	Change in mean Montreal ?ognitive Assessment (MoCA) score	Montreal ?ognitive 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
Secondary	Change in mean Neuropsychiatric Inventory-Clinician (NPI-?) 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
Secondary	Mean Clinical Global Impression Efficacy Index (?GI-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