Clinical Trial of Efficacy and Safety of MMH-MAP in the Treatment of Cognitive Disorders

A Multicenter, Double-blind, Randomized, Parallel Group Placebo-controlled Clinical Trial of Efficacy and Safety of MMH-MAP in the Treatment of Cognitive Disorders in Patients With Ischemic Stroke in the Carotid Arteries

The clinical trial to valuate efficacy and safety of MMH-MAP in the treatment of cognitive disorders in patients with ischemic stroke in the carotid arteries.

Study Overview

• Status: Completed
• Conditions: Cognitive Disorders
• Intervention / Treatment: Drug: Placebo; Drug: MMH-MAP

Detailed Description

Design: double-blind, randomized, parallel group placebo-controlled clinical study of efficacy and safety of MMH-MAP in the treatment of cognitive disorders in patients with ischemic stroke in the carotid arteries.

The study will enroll hospitalized subjects of either gender aged 40-75 years old with verified diagnosis of ischemic stroke in the carotid arteries within 72 hours post debut having moderate cognitive disorders, moderate neurological deficit.

At Visit 1 (day 1) the subject's complaints and medical history will be collected, objective examination, safety laboratory tests (hematology, serum chemistry, urinalysis) will be performed. The investigator will evaluate the patient's level of consciousness using The Glasgow Coma Scale, intensity of cognitive disorders using The Montreal Cognitive Assessment (МоСА), condition using National Institute of Health Stroke Scale (NIHSS) and The Modified Rankin Scale (mRs). Concomitant therapy will be recorded and changes in cerebral CT/MRI will be evaluated. If the subject meets inclusion criteria and has no exclusion criteria, he/she will be randomized to MMH-MAP or Placebo group. The first dose of the study product should be taken within 72 hours post stroke debut.

At Visit 2 (day 12±3, end of hospitalization period - the last day of hospitalization due to the current stroke) complaints will be collected, objective examination findings will be recorded, monitoring of the prescribed and concomitant therapy will be performed, treatment safety, compliance and stroke severity according to NIHSS will be evaluated.

By the end of hospital therapy the subject will be switched to outpatient therapy with continuation of IMP and medical assistance designed for the treatment of stroke and its sequelae.

At Visit 3 (day 45±7 days) the investigator will make a phone call to the subject evaluating the treatment safety.

At final Visit 4 (day 90±7 days) complaints will be collected, objective examination findings will be recorded, monitoring of the prescribed and concomitant therapy will be performed, treatment safety, compliance, condition according to NIHSS will be evaluated, mRs, Clinical Global Impression Efficacy Index (CGI-EI) will be filled. The investigator will perform MoCA testing. Safety laboratory tests (hematology, serum chemistry, urinalysis) will be carried out.

Throughout the study the patient will receive the treatment approved by the decree of the RF Ministry of Health dated 29.12.2012 No. 740n "On approval of standard of special care in cerebral infarction" except for the products specified in section "Forbidden concomitant therapy".

• Study Type: Interventional
• Enrollment (Actual): 246
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Arkhangelsk, Russian Federation, 163001
    • The First City Clinical Hospital named after E.E. Volosevich
  • Arkhangelsk, Russian Federation, 163045
    • Arkhangelsk Regional Clinical Hospital/Neurological Department
  • Belgorod, Russian Federation, 308007
    • Belgorod Regional Clinical Hospital of St. Joasaph
  • Chelyabinsk, Russian Federation, 454021
    • Regional Clinical Hospital # 3
  • Kazan, Russian Federation, 420101
    • Interregional Clinical Diagnostic Center
  • Kazan, Russian Federation, 420012
    • Kazan State Medical University/Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan
  • Kazan, Russian Federation, 420103
    • City Clinical Hospital # 7
  • Krasnodar, Russian Federation, 350086
    • Research Institute - Regional Clinical Hospital # 1 named after Prof. S.V. Ochapovsky
  • Moscow, Russian Federation, 117593
    • Central Clinical Hospital of the Russian Academy of Sciences
  • Moscow, Russian Federation, 115516
    • City Clinical Hospital named after V.M. Buyanov, Moscow Department of Health
  • Nizhny Novgorod, Russian Federation, 603005
    • City Clinical Hospital # 5 of the Nizhegorodskiy District of Nizhny Novgorod
  • Novosibirsk, Russian Federation, 630087
    • Novosibirsk State Regional Clinical Hospital
  • Ryazan, Russian Federation, 390039
    • Regional Clinic Hospital/Emergency cardiology unit with intensive care and resuscitation unit
  • Saint Petersburg, Russian Federation, 192242
    • St. Petersburg Research Institute of Ambulance named after I.I. Janelidze
  • Saint Petersburg, Russian Federation, 194354
    • City Multidisciplinary Hospital # 2
  • Samara, Russian Federation, 443096
    • Samara City Clinical Hospital # 1 named after N.I. Pirogov/Neurological Department
  • Saratov, Russian Federation, 410031
    • Saratov City Clinical Hospital # 9
  • Ulyanovsk, Russian Federation, 432063
    • Ulyanovsk Regional Clinical Hospital/Neurological Department
  • Vladimir, Russian Federation, 600023
    • Regional Clinic Hospital/Neurological department for patients with acute cerebrovascular accident
  • Voronezh, Russian Federation, 394066
    • Voronezh Regional Clinical Hospital # 1
  • Vsevolozhsk, Russian Federation, 188643
    • Vsevolozhsk Clinical Interdistrict Hospital
  • Yaroslavl, Russian Federation, 150030
    • Clinical Hospital # 8/Intensive Care Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age between 40 and 75 years old inclusively.
2. Ischemic stroke in the carotid arteries (I 63) within 72 hours post debut.
3. Moderate cognitive disorders (MoCA < 26).
4. Normal consciousness (Glasgow score 15)
5. Stroke severity 8-12 according to NIHSS.
6. Disability mRs score 2-3.
7. Availability of cerebral CT/MRI within 72 hours post stroke debut.
8. Patients who agreed to use a reliable method of contraception during the study.
9. Patients who have signed the Participant Information Sheet and Informed Consent.

Exclusion Criteria:

1. Current or previous subarachnoidal/parenchymatous/ventricular hemorrhage, cerebral infarction, cerebral tumour.
2. Cerebral CT/MRI findings suggesting cerebral hemorrhage, tumour within 72 hours post stroke debut.
3. Scheduled or completed thrombolytic therapy for the treatment of the current cerebral infarction.

4. Central nervous system (CNS) diseases including:

   • Inflammatory diseases of the central nervous system (G00-G09);
   • Systemic atrophies primarily affecting the central nervous system (G10-G13);
   • Extrapyramidal and movement disorders (G20-G26);
   • Other degenerative diseases of the nervous system (G30-G32);
   • Demyelinating diseases of the CNS (G35-G37);
   • Episodic and paroxysmal disorders (G40-G47);
   • Polyneuropathies and other disorders of the peripheral nervous system (G60-64), with marked movement and/or sensory impairments that cause movement disorders;
   • Hydrocephalus (G91).
5. Head injuries (S00-S09) (including history), accompanied by impaired consciousness, brain contusion or open craniocerebral injuries.
6. Musculoskeletal disorders causing motor disturbances.
7. Dementia (including history) (F00-F03).
8. Malignant neoplasms.
9. Patients previously diagnosed with class IV heart failure (1964 New York Heart Association functional classification), hypothyroidism, or poorly treated diabetes mellitus.
10. Patients having unstable angina or myocardial infarction in the past 6 months.
11. Allergy/ intolerance to any of the components of medications used in the treatment.
12. Malabsorption syndrome, including congenital or acquired lactase deficiency (or any other disaccharidase deficiency) and galactosemia.
13. Any conditions which, according to the investigator opinion, may interfere with the subject's participation in the study.
14. Prior history of non-adherence to a drug regimen, a psychiatric disorder, alcoholism or drug abuse, which, in the opinion of the investigator, can compromise compliance with study protocol.
15. Pregnancy, breast-feeding; childbirth less than 3 months prior to the inclusion in the trial, unwillingness to use contraceptive methods during the trial.
16. Participation in other clinical studies within 3 month prior to enrollment in the study.
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 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
Placebo Comparator: Placebo; Oral administration. For 90 days according to MMH-MAP dosing regimen.	Drug: Placebo; Oral administration
Experimental: MMH-MAP; Oral administration. 2 tablets twice daily (approximately at the same time). The drug is taken outside a meal (between the meals or 15 min prior to meal or fluid intake). Tablets should be held in the mouth until completely dissolved. The overall duration of treatment is 90 days.	Drug: MMH-MAP; Oral administration; Other Names: Prospekta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average MoCA Score.	Montreal Cognitive Assessment Scale (The Montreal Cognitive Assessment, MoCA) will be used to identify moderate cognitive impairment, as well as to assess changes in cognitive functions during therapy. The maximum possible number of points is 30; 26 points or more is considered normal. The minimum score is 0, higher score is better.	On baseline and on 90th day of the treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in NIHSS Score.	NIHSS Scale (National Institutes of Health Stroke Scale) is a scale for assessing the severity of neurological disorders of the acute period of ischemic stroke. The NIHSS scale involves the assessment of a neurological condition by generally accepted methods of clinical examination of reflexes, sensory organs, and the patient's level of consciousness. The results range from minimum indicators - normal or close to normal, to maximum - reflect the degree of neurological damage. The score varies between 0 and 42, lower score is better.	On baseline, on 12th and on 90th days of the treatment.
Percentage of Patients With no Significant Disabilities.	The modified Rankin scale (mRs 0-1) allows to assess the grade of disability after a stroke. The scale includes five grades of disability: from 0 to 5: 0 - no symptoms, 5 - gross disability; bedridden, fecal and urinary incontinence, need for constant assistance by medical staff.	On 90th day of the treatment.
Therapeutic and Side Effects, Efficacy Index.	According to Clinical Global Impression Efficacy Index (CGI-EI).CGI-EI is filled out by an investigator. It is necessary to indicate the level of efficacy of the therapy and the grade of safety of the therapy and circle the index values at the intersection of the selected lines. Evaluation of the response to treatment should take into account both therapeutic efficacy and treatment-related side effects. Side effects score varies from 1 to 4 (lower is better). Therapeutic effect score varies from 1 to 4 (higher is better). The efficacy index is "Therapeutic effect score" divided by "Side effects score", so efficacy index varies from 0.25 to 4 (higher is better).	On 90th day of the treatment period.
Presence of Adverse Events (AEs).	Based on medical records. Outcome measure represents the amount of participants having at least one adverse event on record.	For 90 days of the treatment period.
Percentage of Patients With Complication of Cerebral Infarction.	Based on medical records. The sequelae of cerebral infarction (severe infections - hospital-acquired pneumonia, uroinfection; deep venous thrombosis, PATE; epileptic episodes).	For 90 days of the treatment period.
Death Rate.	Based on medical records. Frequency of all-cause mortality outcomes.	For 90 days of the treatment period.
Changes in Vital Signs (Pulse Rate (Heart Rate)).	Based on medical records. Vital signs will be measured in a medical setting.	Visit 1 (day 1), Visit 2 (day 12), and Visit 4 (day 90).
Changes in Vital Signs (Respiration Rate (Breathing Rate)).	Based on medical records. Vital signs will be measured in a medical setting.	Visit 1 (day 1), Visit 2 (day 12), and Visit 4 (day 90)
Changes in Vital Signs (Blood Pressure).	Based on medical records. Vital signs are measured in a medical setting. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) are presented.	Visit 1 (day 1), Visit 2 (day 12), and Visit 4 (day 90).
Percentage of Patients With Clinically Significant Abnormal Laboratory Data.	Based on medical records. Laboratory tests include the following parameters (absolute and relative values): hematology, biochemistry and urinalysis. Laboratory tests will be made by central laboratory. Hemoglobin: less than or equal to (<=) 115 grams per liter (g/L); greater than or equal to (>=)185 g/L; decreased from baseline (DFB) >=20 g/L Hematocrit: <=0.37 volume/volume (v/v); >=0.55 v/v Erythrocytes: >=6 Tera/L Leukocytes: >=16.0 Giga/L Neutrophils: <1.0 Giga/L (B); Lymphocytes: greater than (>) 4.0 Giga/L Monocytes: >0.7 Giga/L Basophils: >0.1 Giga/L Eosinophils: >0.5 Giga/L or >upper limit of normal (ULN) (if ULN >=0.5 Giga/L) Sodium: <=129 millimoles (mmol)/L; >=160 mmol/L Potassium: <3 mmol/L; >=5.5 mmol/L Alanine Aminotransferase (ALT): >3 ULN Aspartate aminotransferase (AST): >3 ULN Alkaline phosphatase: >1.5 ULN Bilirubin: >1.5 ULN Creatinine: >=150 micromoles per liter (mcmol/L); >=30% change from baseline.	On baseline and on 90th day of the treatment.
Percentage of Patients With Recurring Cerebral Infarction.	The percentage of patients with recurrent cerebral infarction for 90 days of the treatment period is estimated from medical records.	For 90 days of the treatment period.

Collaborators and Investigators

• Sponsor: Materia Medica Holding

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2019
• Primary Completion (Actual): February 7, 2023
• Study Completion (Actual): February 7, 2023

Study Registration Dates

• First Submitted: February 27, 2020
• First Submitted That Met QC Criteria: March 3, 2020
• First Posted (Actual): March 4, 2020

Study Record Updates

• Last Update Posted (Actual): October 28, 2024
• Last Update Submitted That Met QC Criteria: August 12, 2024
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognitive Dysfunction; Cognition Disorders
• Other Study ID Numbers: MMH-MAP-002

Drug and device information, study documents

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