Clinical Trial of Efficacy and Safety of MMH-MAP in the Treatment of Mild Cognitive Impairment in Early Recovery Stage After Ischemic Stroke

February 5, 2021 updated by: Materia Medica Holding

Multicenter Double-blind Placebo-controlled Randomized Parallel-group Clinical Study of Efficacy and Safety of MMH-MAP in the Treatment of Mild Cognitive Impairment in Subjects in Early Rehabilitation Period of Ischemic Stroke

The purpose of this study is:

  • to evaluate efficacy of MMH-MAP in the treatment of mild cognitive impairment in subjects in early rehabilitation period of ischemic stroke
  • to evaluate safety of MMH-MAP in the treatment of mild cognitive impairment in subjects in early rehabilitation period of ischemic stroke

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A double-blind, placebo-controlled randomized clinical trial in parallel groups.

The study patients are subjects of either gender, aged 45-80 years old, after an ischemic stroke within 3-6 months prior to enrollment and confirmed by neuroimaging, having mild cognitive impairment.

After the patients provide signed Participant Information Sheet and Informed Consent, they will be interviewed for complaints and medical history and undergo physical examination and laboratory tests. The doctor will rate the severity of patients' cognitive impairments on the Mini Mental State Examination (MMSE) scale and Montreal Cognitive Assessment (MoCA) scale, assess their performance in activities of daily living on the Barthel Index scale [Collin C, Wade DT, Davies S, Horne V. "The Barthel ADL Index: a reliability study." Int Disability Study.1988;10:61-63.], and administer the Stroke Specific Quality of Life Scale (SS-QOL) questionnaire [Williams LS, Weinberger M, Harris LE, Clark DO, Biller J. Development of a stroke-specific quality of life scale. Stroke 1999 Jul;30(7):1362-9]. Eligible participants will have to have moderate cognitive impairments (MMSE score - at least 21 and MoCA - less than 26). Therapy received by patients for their co-morbidities and primary diagnosis will be recorded. All women of childbearing potential will be administered pregnancy tests.

If a patient meets all inclusion criteria and does not have any exclusion criteria at Visit 1, he/she is randomized to one of the two groups: group 1 will receive MMH-MAP at 2 tablets twice daily; group 2 will receive Placebo using the study product dosing regimen. The total duration of follow-up and treatment will be 28 weeks, which will include 5 additional visits.

At Visit 2 (Week 4±7 days), the doctor records patients' complaints and physical examination data, reviews the progress of study and basic and concomitant therapy, and assesses treatment safety and patient compliance with treatment.

At Visit 3 (Week 8±7 days), Visit 4 (Week 16±7 days), and Visit 5 (Week 24±7 days), the doctor assesses patients' cognitive impairments (MoCA) and performance in activities of daily living (the Barthel Index). The patients complete the SS-QOL questionnaire.

At Visit 5 (Week 24±7 days), the doctor will additionally complete the Clinical Global Impression Efficacy Index (CGI-EI) scale [Guy W, editor. ECDEU Assessment Manual for Psychopharmacology. 1976 Rockville, MD, U.S. Department of Health, Education, and Welfare] and collect samples for laboratory testing. The patient stops taking the study drug.

After four weeks following the end of study therapy patients complete a follow-up visit -Visit 6 (Week 28±7 days). The patients are interviewed for complaints and undergo physical examination, with a check on their concomitant and primary therapies as well as on the safety of study treatment. The doctor assesses patients' cognitive impairments (MoCA) and performance in activities of daily living (the Barthel Index) and administers the SS-QOL questionnaire.

The total length of the observation period will be 28 weeks. During the study, symptomatic therapy and therapy for underlying chronic conditions are allowed with the exception of the drugs indicated in the section "Prohibited Concomitant Treatment".

Study Type

Interventional

Enrollment (Actual)

276

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Russian Federation
      • Arkhangel'sk, Russian Federation, 163045
        • Arkhangelsk Regional Clinical Hospital
      • Belgorod, Russian Federation, 308007
        • Belgorod Regional Clinical Hospital of St. Joseph
      • Bryansk, Russian Federation, 241004
        • Non-State Healthcare Institution "Divisional Hospital at the Bryansk-2 station of the open joint-stock company Russian Railways"
      • Bryansk, Russian Federation, 241033
        • Bryansk Regional Hospital № 1
      • Kazan, Russian Federation, 420012
        • Federal State Budgetary Educational Institution of Higher Education "Kazan Medical University" of the Ministry of Healthcare of the Russian Federation
      • Krasnodar, Russian Federation, 350086
        • Scientific-Research Institute - Regional Clinical Hospital №1 named after Professor S.V. Ochapovsky
      • Moscow, Russian Federation, 115516
        • The State Budget Health Care institution of Moscow the City "City clinical hospital No. 12 of the Administration of Health Care of Moscow City"
      • Moscow, Russian Federation, 119049
        • State Budgetary Institution of Healthcare of the City of Moscow City Clinical Hospital No. 1 named after. N.I. Pirogov Moscow Department of Health
      • Moscow, Russian Federation, 127206
        • City Clinical Hospital named after SI. Spasokokukotsky Department of Health of Moscow
      • Nizhny Novgorod, Russian Federation, 603126
        • State budgetary institution of public health services of the Nizhniy Novgorod region "Nizhegorod Regional Clinical Hospital named after NA Semashko"
      • Nizhny Novgorod, Russian Federation, 603005
        • City Clinical Hospital №5 of Nizhny Novgorod region of Nizhny Novgorod
      • Nizhny Novgorod, Russian Federation, 603005
        • Privolzhskiy Research Medical University
      • Pyatigorsk, Russian Federation, 357538
        • Pyatigorsk City Clinical Hospital № 2
      • Ryazan', Russian Federation, 390026
        • Ryazan State Medical University named after academician I.P. Pavlov
      • Saint Petersburg, Russian Federation, 194291
        • Leningrad Regional Clinical Hospital
      • Saint Petersburg, Russian Federation, 192242
        • St. Petersburg I. I. Dzhanelidze Research Institute of Emergency Medicine
      • Samara, Russian Federation, 443096
        • State budgetary institution of health care of the Samara region "Samara City Clinical Hospital № 1 named after NI Pirogov"
      • Saransk, Russian Federation, 430032
        • Republican Clinical Hospital No4
      • Saratov, Russian Federation, 410012
        • Saratov State Medical University named after V. I. Razumovsky
      • Sestroretsk, Russian Federation, 197706
        • St. Petersburg State Budgetary Institution "City Hospital No. 40 in the Kurortny District"
      • Smolensk, Russian Federation, 214018
        • Smolensk State Medical University
      • Tver, Russian Federation, 170026
        • State budgetary institution of health care of the Tver region "Regional Clinical Treatment and Rehabilitation Center"
      • Ulyanovsk, Russian Federation, 432063
        • State Healthcare Institution Ulyanovsk Regional Clinical Hospital
      • Vladimir, Russian Federation, 600023
        • State budgetary health care institution of the Vladimir region "Regional Clinical Hospital"
      • Volgograd, Russian Federation, 400131
        • Volgograd State Medical University
      • Voronezh, Russian Federation, 394066
        • Voronezh Regional Clinical Hospital № 1
      • Vsevolozhsk, Russian Federation, 188643
        • Vsevolozhsk Clinical Interdistrict Hospital
      • Yaroslavl, Russian Federation, 150030
        • State Institution of Health of the Yaroslavl Region Clinical Hospital No. 8

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients of either sex, aged 45 to 80 years old inclusively.
  2. Patients with a history of one stroke sustained 3 to 6 months prior to study entry and confirmed by neuroimaging.
  3. Patients with cognitive impairment (MoCA score < 26).
  4. Patients with moderate performance in activities of daily living (Barthel score = 61-80).
  5. Agreement to use a reliable method of birth control for the duration of the study (men and women of reproductive potential).
  6. Availability of signed patient information sheet (Informed Consent form) for participation in the clinical trial.

Exclusion Criteria:

  1. Patients with a history of subarachnoid/parenchymatous/ventricular hemorrhage, brain neoplasm, or any other condition which has caused neurological dysfunction.

  2. History of central nervous system (CNS) disorders, including:

    • inflammatory diseases of the CNS (G00-G09)
    • systemic atrophies primarily affecting the CNS (G10-G13)
    • extrapyramidal and movement disorders (G20-G26)
    • other degenerative diseases of the nervous system (G30-G32)
    • demyelinating diseases of the CNS (G35-G37)
    • epilepsy (G40-41)
    • polyneuropathies and other disorders of the peripheral nervous system (G60-64), with marked movement and/or sensory impairments that cause movement disorders
    • diseases of neuromuscular junction and muscle (G70-73)
    • hydrocephalus (G91)
    • compression of brain (G93.5).
  3. Dementia (20 or less on the MMSE score).
  4. Speech disorders affecting investigator-patient communication.
  5. Prior diagnosis of heart failure defined by the New York Heart Association classification (1964) as IV Functional Classification or poorly treated hypothyroidism or diabetes mellitus.
  6. Patients having unstable angina or myocardial infarction in the past 6 months.
  7. History/suspicion of oncology of any location (except for benign neoplasms).
  8. Any other co-morbidity which, in the opinion of the investigator, may affect patient participation in the clinical trial.
  9. Patients allergic to/intolerant of any components of the study treatment.
  10. Patients with hereditary lactose intolerance.
  11. Malabsorption syndrome, including congenital or acquired lactase deficiency (or any other disaccharidase deficiency) and galactosemia.
  12. Pregnancy, breast-feeding or unwillingness to use birth control during the study.
  13. Patients who, from the investigator's point of view, will not comply with the observation requirements of the study or adhere to study drug dosing regimens.
  14. Patients with a history of non-adherence to medication; mental disorder (except for cognitive deficits); or alcoholism or abuse of psychoactive substances, which, in the investigator's opinion, will compromise compliance with study procedures.
  15. Patients who have used medications listed in 'Prohibited Concomitant Treatment' in the past week.
  16. Participation in other clinical trials in the previous 3 months.
  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 MATERIA MEDICA HOLDING (i.e. the company's employees, temporary contract workers, appointed officials responsible for carrying out the research or immediate relatives of the aforementioned).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: MMH-MAP
Tablet for oral use. Dose per administration: 2 tablets. 2 tablets twice daily (4 tablets/day). The tablets should be held in mouth without chewing until complete dissolution. The duration of treatment will be 24 weeks.
Drug: MMH-MAP
Oral administration
Placebo Comparator: Placebo
Placebo for 24 weeks, according to the MMH-MAP dosing regimen.
Drug: Placebo
Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Patients With Improved Cognitive Function (The Montreal Cognitive Assessment Test Total Score of the Baseline +1 or More)
Time Frame: 24 weeks of the treatment as compared to the baseline
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.
24 weeks of the treatment as compared to the baseline

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in MoCA (The Montreal Cognitive Assessment Test) Score
Time Frame: 24 weeks of the treatment as compared to the baseline
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.
24 weeks of the treatment as compared to the baseline
Percentage of Patients With Improved Performance in Activities of Daily Living (Barthel Index Score of the Baseline + 5 or More)
Time Frame: 24 weeks of the treatment as compared to the baseline
Scale for measurement of performance in activities of daily living (ADL).The maximum score is 100. A score of 91-99 stands for mild dependence in ADL performance, 61-90 - for moderate dependence in ADL performance, 21-60 - for severe dependence in ADL performance, 0-20 - for complete dependence in ADL performance. Higher values represent a better outcome.
24 weeks of the treatment as compared to the baseline
Change in Barthel Index Score
Time Frame: 24 weeks of the treatment as compared to the baseline
Scale for measurement of performance in activities of daily living (ADL).The maximum score is 100. A score of 91-99 stands for mild dependence in ADL performance, 61-90 - for moderate dependence in ADL performance, 21-60 - for severe dependence in ADL performance, 0-20 - for complete dependence in ADL performance. Higher values represent a better outcome.
24 weeks of the treatment as compared to the baseline
Change in SS-QOL (Stroke Specific Quality of Life Scale) Total Score
Time Frame: 24 weeks of the treatment as compared to the baseline
Scale for assessment of health-related quality of life. The scale consists of 49 items in the 12 domains. Each domain consists of 3 to 10 items that are averaged to generate an overall score. Total score minimum value is 1 and maximum value is 245. Higher values represent a better outcome.
24 weeks of the treatment as compared to the baseline
The CGI-EI (Clinical Global Impression Efficacy Index) Score
Time Frame: 24 weeks of the treatment
Rating scale for assessment of the therapeutic effect of treatment and associated side effects. The scale consists of 2 items: therapeutic effect and side effects. Scores in therapeutic effect range from 1 (marked improvement) to 13 (unchanged or worse). Scores in side effects range from 0 (no side effects) to 3 (side effects outweigh therapeutic effects). Efficacy index ranges between 0 and 16. Higher values represent a worse result.
24 weeks of the treatment
Change in MoCA (The Montreal Cognitive Assessment Test) Score During Follow-up
Time Frame: 24 and 28 weeks of the study
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.
24 and 28 weeks of the study
Change in Barthel Index Score During Follow-up
Time Frame: 24 and 28 weeks of the study
Scale for measurement of performance in activities of daily living (ADL). The maximum score is 100. A score of 91-99 stands for mild dependence in ADL performance, 61-90 - for moderate dependence in ADL performance, 21-60 - for severe dependence in ADL performance, 0-20 - for complete dependence in ADL performance. Higher values represent a better outcome.
24 and 28 weeks of the study
Change in Total SS-QOL (Stroke Specific Quality of Life Scale) Score During Follow-up
Time Frame: 24 and 28 weeks of the study
Scale for assessment of health-related quality of life. The scale consists of 49 items in the 12 domains.Each domain consists of 3 to 10 items that are averaged to generate an overall score.Total score minimum value is 1 and maximum value is 245.Higher values represent a better outcome.
24 and 28 weeks of the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Materia Medica Holding

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 19, 2018

Primary Completion (Actual)

January 27, 2020

Study Completion (Actual)

January 27, 2020

Study Registration Dates

First Submitted

November 11, 2018

First Submitted That Met QC Criteria

January 23, 2019

First Posted (Actual)

January 24, 2019

Study Record Updates

Last Update Posted (Actual)

February 23, 2021

Last Update Submitted That Met QC Criteria

February 5, 2021

Last Verified

August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MMH-MAP-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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