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

Mild Cognitive Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03815292
• Other study ID #: MMH-MAP-001
• Status: Completed
• Phase: Phase 3
• Start date: October 19, 2018
• Est. completion date: January 27, 2020

Study information

• Verified date: August 2019
• Source: Materia Medica Holding
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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".

Recruitment information / eligibility

• Status: Completed
• Enrollment: 276
• Est. completion date: January 27, 2020
• Est. primary completion date: January 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 80 Years

Eligibility

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).

Related Conditions & MeSH terms

• Cerebral Infarction
• Cognitive Dysfunction
• Ischemia
• Ischemic Stroke
• Mild Cognitive Impairment
• Stroke

Intervention

Drug:
• MMH-MAP
Oral administration
• Placebo
Oral administration

Locations

Country	Name	City	State
Russian Federation	Arkhangelsk Regional Clinical Hospital	Arkhangel'sk
Russian Federation	Belgorod Regional Clinical Hospital of St. Joseph	Belgorod
Russian Federation	Bryansk Regional Hospital ? 1	Bryansk
Russian Federation	Non-State Healthcare Institution "Divisional Hospital at the Bryansk-2 station of the open joint-stock company Russian Railways"	Bryansk
Russian Federation	Federal State Budgetary Educational Institution of Higher Education "Kazan Medical University" of the Ministry of Healthcare of the Russian Federation	Kazan
Russian Federation	Scientific-Research Institute - Regional Clinical Hospital ?1 named after Professor S.V. Ochapovsky	Krasnodar
Russian Federation	City Clinical Hospital named after SI. Spasokokukotsky Department of Health of Moscow	Moscow
Russian Federation	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	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	City Clinical Hospital ?5 of Nizhny Novgorod region of Nizhny Novgorod	Nizhny Novgorod
Russian Federation	Privolzhskiy Research Medical University	Nizhny Novgorod
Russian Federation	State budgetary institution of public health services of the Nizhniy Novgorod region "Nizhegorod Regional Clinical Hospital named after NA Semashko"	Nizhny Novgorod
Russian Federation	Pyatigorsk City Clinical Hospital ? 2	Pyatigorsk
Russian Federation	Ryazan State Medical University named after academician I.P. Pavlov	Ryazan'
Russian Federation	Leningrad Regional Clinical Hospital	Saint Petersburg
Russian Federation	St. Petersburg I. I. Dzhanelidze Research Institute of Emergency Medicine	Saint Petersburg
Russian Federation	State budgetary institution of health care of the Samara region "Samara City Clinical Hospital ? 1 named after NI Pirogov"	Samara
Russian Federation	Republican Clinical Hospital ?4	Saransk
Russian Federation	Saratov State Medical University named after V. I. Razumovsky	Saratov
Russian Federation	St. Petersburg State Budgetary Institution "City Hospital No. 40 in the Kurortny District"	Sestroretsk
Russian Federation	Smolensk State Medical University	Smolensk
Russian Federation	State budgetary institution of health care of the Tver region "Regional Clinical Treatment and Rehabilitation Center"	Tver
Russian Federation	State Healthcare Institution Ulyanovsk Regional Clinical Hospital	Ulyanovsk
Russian Federation	State budgetary health care institution of the Vladimir region "Regional Clinical Hospital"	Vladimir
Russian Federation	Volgograd State Medical University	Volgograd
Russian Federation	Voronezh Regional Clinical Hospital ? 1	Voronezh
Russian Federation	Vsevolozhsk Clinical Interdistrict Hospital	Vsevolozhsk
Russian Federation	State Institution of Health of the Yaroslavl Region Clinical Hospital No. 8	Yaroslavl

Sponsors (1)

Lead Sponsor	Collaborator
Materia Medica Holding

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in MoCA (The Montreal Cognitive Assessment Test) Score	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	Percentage of Patients With Improved Performance in Activities of Daily Living (Barthel Index Score of the Baseline + 5 or More)	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
Other	Change in Barthel Index Score	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
Other	Change in SS-QOL (Stroke Specific Quality of Life Scale) Total Score	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
Other	The CGI-EI (Clinical Global Impression Efficacy Index) Score	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
Other	Change in MoCA (The Montreal Cognitive Assessment Test) Score During Follow-up	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
Other	Change in Barthel Index Score During Follow-up	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
Other	Change in Total SS-QOL (Stroke Specific Quality of Life Scale) Score During Follow-up	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
Primary	Percentage of Patients With Improved Cognitive Function (The Montreal Cognitive Assessment Test Total Score of the Baseline +1 or More)	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