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

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Vascular Dementia

Intervention / Treatment
-----------------
* Drug: Cerebrolysin
* Drug: 0.9% Saline Solution


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cerebrolysin<br> | Drug: Cerebrolysin<br> <br> |
| Placebo Comparator: 0.9% Saline Solution<br> | Drug: 0.9% Saline Solution<br> <br> |

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 |