A Clinical Trial to Evaluate the Safety and Efficacy of 20 ml Cerebrolysin in Patients With Vascular Dementia (VascDem)

A Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of 20 ml Cerebrolysin in Patients With Vascular Dementia

This clinical trial was performed to assess the clinical efficacy and safety of two 4 week treatment courses of daily intravenous administration of Cerebrolysin (20mL [milliliter] IV [intravenous] per day). The study was performed as prospective, randomised, double-blind, placebo-controlled, parallel group, multicentre study with 2 study groups.

Group 1: 20 mL Cerebrolysin and 100 mg (milligram) acetylsalicylic acid Group 2: Placebo (0.9% NaCl [sodium chloride]) and 100 mg acetylsalicylic acid The study drug was given once daily by intravenous infusion (20ml in 250ml saline solution) for 4 weeks on five consecutive days per week. This treatment regimen was repeated after a two-month treatment-free interval. Acetylsalicylic acid was given orally, once daily throughout the study duration of 24 weeks.

Altogether five clinical evaluation visits at Baseline (day 0) and at week 4, 12, 16, and 24 were necessary.

Study Overview

• Status: Completed
• Conditions: Vascular Dementia
• Intervention / Treatment: Drug: Cerebrolysin; Drug: 0.9% Saline Solution

• Study Type: Interventional
• Enrollment (Actual): 242
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Chita, Russian Federation
    • Chita State Medical Academy/Regional Psychiatric Hospital No. 2
  • Chita, Russian Federation
    • Chita State Medical Academy/Veterans Hospital
  • Irkutsk, Russian Federation
    • Irkutsk State Institute of Postgraduate Education/Regional Clinical Hospital
  • Kazan, Russian Federation
    • Kazan State Medical University/Municipal Clinical Hospital No. 6
  • Kazan, Russian Federation
    • Kazan State Medical University/Republican Clinical Hospital
  • Kursk, Russian Federation
    • Kursk Medical University/Kursk Regional Clinical Hospital
  • Moscow, Russian Federation
    • I. M. Sechenov Moscow Medical Academy
  • Moscow, Russian Federation
    • Mental Health Research Center of RAMS/Psychiatric Clinical Hospital No. 15
  • Moscow, Russian Federation
    • Mental Health Research Center of RAMS
  • Moscow, Russian Federation
    • Russian Medical Academy of Postgraduate Education/S. P. Botkin Municipal Clinical Hospital
  • Moscow, Russian Federation
    • Russian State Medical University/N. I. Pirogov Municipal Clinical Hospital No. 1
  • Moscow, Russian Federation
    • Scientific Research Institute of Neurology of RAMS
  • Nizhniy Novgorod, Russian Federation
    • Municipal Clinical Hospital No. 5
  • Nizhniy Novgorod, Russian Federation
    • N. A. Semashko Nizhniy Novgorod Regional Clinical Hospital
  • Reutov, Russian Federation
    • Central Municipal Hospital
  • Saratov, Russian Federation
    • Saratov Regional Psychiatric Hospital of Snt. Sofia
  • St. Petersburg, Russian Federation
    • I. P. Pavlov St. Petersburg State Medical University
  • St. Petersburg, Russian Federation
    • S. M. Kirkov Medical Military Academy of the Ministry of Defense of RF
  • St. Petersburg, Russian Federation
    • V. M. Bekhterev St. Petersburg Scientific Research Psychoneurological Institute
  • Ufa, Russian Federation
    • Bashkirian State Medical University/Emergency Medical Care Hospital
  • Yaroslavl, Russian Federation
    • Yaroslavl State Medical Academy/Yaroslavl Clinical Hospital No. 8

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men or post-menopausal women between 50 and 85 years
• Clinical diagnosis of vascular dementia according to NINDS-AIREN criteria
• CT or MRI results compatible with clinical diagnosis
• MMSE score between 10 and 24, both inclusive
• Modified Hachinski Ischemic Score >4
• Hamilton Depression Scale score of less than or equal to 15
• Adequate visual and auditory acuity to allow neuropsychological testing
• Informed consent given by the patient and/or the next-of-kin

Exclusion Criteria:

• Gastric ulcer associated with intolerance of acetylsalicylic acid treatment
• Severe psychotic features, schizophrenia, depression, agitation or behavioral problems within the last three months that could lead to difficulty complying with the protocol
• Any severe systemic illness or unstable medical condition that could lead to difficulty complying with the protocol or significantly limits life span.
• Patients who in the investigator's opinion, would not comply with study procedures
• Any significant neurological disease other than vascular dementia, such as Parkinson's disease, epilepsy, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, or multiple sclerosis
• History of alcohol or substance abuse or dependence within the past two years
• Patients with a history of systemic cancer within the past two years
• Severe congestive heart failure or malignant, uncontrollable hypertension
• Participation in a clinical trial with an investigational drug in the past four weeks

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
Experimental: Cerebrolysin	Drug: Cerebrolysin
Placebo Comparator: 0.9% Saline Solution	Drug: 0.9% Saline Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in ADAS-cog+ (Alzheimer's Disease Assesment Scale - Cognitive Subpart) at Week 24	The ADAS-COG+ is a psychometric instrument used to evaluate memory, attention, reasoning, language, orientation and praxis. The score ranges from 0 to 85 with 85 being the worst score. A negative change indicates cognitive improvement.	baseline and week 24
CIBIC+ (Clinicians Interview-based Impression of Change) Score at Week 24	This rating scale is based on the health care provider's "general clinical impressions" with the informant input (i.e. family members). It evaluates global function and is scored from 1 (marked improvement) to 7 (marked worsening).	week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in ADAS-COG+ (Alzheimer's Disease Assessment Scale Cognitive Subpart)	The modified Alzheimer's Disease Assessment Scale - Cognitive (ADAS-COG+) is a psychometric instrument used by a neuropsychologist that evaluates memory, attention, reasoning, language, orientation and praxis.	week 4, 12, 16
ADAS-COG+ Response	A patient with an improvement from baseline of ≥ 4 points in the ADAS-COG+ score at a particular visit is considered to have an ADAS-COG+ response at that visit.	week 4, 12, 16, 24
Change From Baseline for Original ADAS-COG	The Original Alzheimer's Disease Assessment Scale - Cognitive (ADAS-COG) is comprised of items 1-11 of the modified ADAS-COG+.	week 4, 12, 16, 24
CIBIC+ Score	The Clinician Interview-based Impression of Change (CIBIC+) score is assigned by an experienced physician familiar with the manifestations of dementia after interviewing the patient and the caregiver.	week 4, 12, 16
CIBIC+ Response	A patient with a CIBIC+ score of 1 to 3 at a particular visit is considered to have a CIBIC+ response at that visit. Patients with a score of 0, indicating that the assessment was not performed, are considered to be non-responders.	week 4, 12, 16, 24
CIBIS+ (Clinicians Interview-Based Impression of Severity)	The Clinician Interview-based Impression of Disease Severity (CIBIS+) score is assigned by an experienced physician, familiar with the manifestations of dementia, after interviewing the patient and the caregiver.	week 24
Change From Baseline in MMSE (Mini-Mental State Examination) Score	The Mini-Mental State Examination (MMSE) is a frequently used screening instrument for clinical trials conducted in patients with Alzheimer's Disease. It evaluates orientation, registration, attention and calculation, recall and language.	week 4, 12, 16, 24
Change From Baseline in ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale)	The ADCS-ADL is a measure of functional disability. The ADCS-ADL assessment of activities of daily living is based on an interview with the caregiver.	week 4, 12, 16, 24
Change From Baseline in Trail-making Test	The Trail-making test is a frequently used instrument for the assessment of executive function.	week 4, 12, 16, 24
Change From Baseline in Clock-drawing Test	The Clock-drawing test is a frequently used screening instrument for dementia drug studies. It evaluates executive function of demented patients.	week 4, 12, 16, 24
Combined Response, i.e. Response in ADAS-COG+ and CIBIC+		week 4, 12, 16, 24

Collaborators and Investigators

• Sponsor: Ever Neuro Pharma GmbH
• Collaborators: acromion GmbH; Geny Research Corp.
• Investigators: Study Director: Philipp Novak, PhD, EBEWE Neuro Pharma

Publications and helpful links

General Publications

• Guekht AB, Moessler H, Novak PH, Gusev EI; Cerebrolysin Investigators. Cerebrolysin in vascular dementia: improvement of clinical outcome in a randomized, double-blind, placebo-controlled multicenter trial. J Stroke Cerebrovasc Dis. 2011 Jul-Aug;20(4):310-8. doi: 10.1016/j.jstrokecerebrovasdis.2010.01.012. Epub 2010 Jul 24.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Study Completion (Actual): August 1, 2007

Study Registration Dates

• First Submitted: April 20, 2009
• First Submitted That Met QC Criteria: June 10, 2009
• First Posted (Estimated): July 28, 2009

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Neurocognitive Disorders; Intracranial Arterial Diseases; Intracranial Arteriosclerosis; Leukoencephalopathies; Dementia; Dementia, Vascular; Physiological Effects of Drugs; Neuroprotective Agents; Protective Agents; Nootropic Agents; Cerebrolysin
• Other Study ID Numbers: EBE-RU-051201