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

• Sponsor: Ever Neuro Pharma GmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00947531
• Collaborator: acromion GmbH (Industry), Geny Research Corp. (Other)
• Enrollment: 242
• Locations: 21
• Arms: 2
• Duration (Months): 10
• Patients Per Site: 11.5
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Vascular Dementia	Drug: Cerebrolysin; Drug: 0.9% Saline Solution	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 242 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: Oct 1, 2006
• Actual Study Completion Date: Aug 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cerebrolysin	Drug: Cerebrolysin
Placebo Comparator: 0.9% Saline Solution	Drug: 0.9% Saline Solution

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in ADAS-cog+ (Alzheimer's Disease Assesment Scale - Cognitive Subpart) at Week 24 [baseline and 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.

2. CIBIC+ (Clinicians Interview-based Impression of Change) Score at Week 24 [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).

Secondary Outcome Measures

1. Change From Baseline in ADAS-COG+ (Alzheimer's Disease Assessment Scale Cognitive Subpart) [week 4, 12, 16]

   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.

2. ADAS-COG+ Response [week 4, 12, 16, 24]

   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.

3. Change From Baseline for Original ADAS-COG [week 4, 12, 16, 24]

   The Original Alzheimer's Disease Assessment Scale - Cognitive (ADAS-COG) is comprised of items 1-11 of the modified ADAS-COG+.

4. CIBIC+ Score [week 4, 12, 16]

   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.

5. CIBIC+ Response [week 4, 12, 16, 24]

   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.

6. CIBIS+ (Clinicians Interview-Based Impression of Severity) [week 24]

   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.

7. Change From Baseline in MMSE (Mini-Mental State Examination) Score [week 4, 12, 16, 24]

   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.

8. Change From Baseline in ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale) [week 4, 12, 16, 24]

   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.

9. Change From Baseline in Trail-making Test [week 4, 12, 16, 24]

   The Trail-making test is a frequently used instrument for the assessment of executive function.

10. Change From Baseline in Clock-drawing Test [week 4, 12, 16, 24]

    The Clock-drawing test is a frequently used screening instrument for dementia drug studies. It evaluates executive function of demented patients.

11. Combined Response, i.e. Response in ADAS-COG+ and CIBIC+ [week 4, 12, 16, 24]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chita State Medical Academy/Regional Psychiatric Hospital No. 2	Chita		Russian Federation
2	Chita State Medical Academy/Veterans Hospital	Chita		Russian Federation
3	Irkutsk State Institute of Postgraduate Education/Regional Clinical Hospital	Irkutsk		Russian Federation
4	Kazan State Medical University/Municipal Clinical Hospital No. 6	Kazan		Russian Federation
5	Kazan State Medical University/Republican Clinical Hospital	Kazan		Russian Federation
6	Kursk Medical University/Kursk Regional Clinical Hospital	Kursk		Russian Federation
7	I. M. Sechenov Moscow Medical Academy	Moscow		Russian Federation
8	Mental Health Research Center of RAMS/Psychiatric Clinical Hospital No. 15	Moscow		Russian Federation
9	Mental Health Research Center of RAMS	Moscow		Russian Federation
10	Russian Medical Academy of Postgraduate Education/S. P. Botkin Municipal Clinical Hospital	Moscow		Russian Federation
11	Russian State Medical University/N. I. Pirogov Municipal Clinical Hospital No. 1	Moscow		Russian Federation
12	Scientific Research Institute of Neurology of RAMS	Moscow		Russian Federation
13	Municipal Clinical Hospital No. 5	Nizhniy Novgorod		Russian Federation
14	N. A. Semashko Nizhniy Novgorod Regional Clinical Hospital	Nizhniy Novgorod		Russian Federation
15	Central Municipal Hospital	Reutov		Russian Federation
16	Saratov Regional Psychiatric Hospital of Snt. Sofia	Saratov		Russian Federation
17	I. P. Pavlov St. Petersburg State Medical University	St. Petersburg		Russian Federation
18	S. M. Kirkov Medical Military Academy of the Ministry of Defense of RF	St. Petersburg		Russian Federation
19	V. M. Bekhterev St. Petersburg Scientific Research Psychoneurological Institute	St. Petersburg		Russian Federation
20	Bashkirian State Medical University/Emergency Medical Care Hospital	Ufa		Russian Federation
21	Yaroslavl State Medical Academy/Yaroslavl Clinical Hospital No. 8	Yaroslavl		Russian Federation

Sponsors and Collaborators

• Ever Neuro Pharma GmbH
• acromion GmbH
• Geny Research Corp.

Investigators

• Study Director: Philipp Novak, PhD, EBEWE Neuro Pharma

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00947531
• Other Study ID Numbers: EBE-RU-051201
• First Posted: Jul 28, 2009
• Last Update Posted: Aug 3, 2020
• Last Verified: Jul 1, 2020

• Additional relevant MeSH terms: Dementia; Dementia, Vascular; Cerebrolysin

Study Results

Participant Flow

Recruitment Details	Date of recruitment period: 24-Oct-2006 - 02-Feb-2007 Type of location: Hospitals, Medical Universities, Medical Military Academy, Research Institutes
Pre-assignment Detail	Patients were excluded from the trial before assignment to a group when not all inclusion criteria were met or when exclusion criteria were applicable.

Arm/Group Title	Cerebrolysin	0.9% Saline Solution
Arm/Group Description
Period Title: Overall Study
STARTED	121	121
COMPLETED	107	110
NOT COMPLETED	14	11

Baseline Characteristics

Arm/Group Title	Cerebrolysin	0.9% Saline Solution	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	121	121	242
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	38 31.4%	39 32.2%	77 31.8%
>=65 years	83 68.6%	82 67.8%	165 68.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.1 (8.0)	67.6 (8.0)	67.3 (8.0)
Sex: Female, Male (Count of Participants)
Female	82 67.8%	72 59.5%	154 63.6%
Male	39 32.2%	49 40.5%	88 36.4%
Region of Enrollment (participants) [Number]
Russian Federation	121 100%	121 100%	242 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in ADAS-cog+ (Alzheimer's Disease Assesment Scale - Cognitive Subpart) at Week 24
Description	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.
Time Frame	baseline and week 24

Outcome Measure Data

Analysis Population Description

The primary and confirmatory analysis is based on the ITT analysis set. The LOCF method is applied to account for missing data. The ITT analysis set consists of all randomized patients, who received at least one dose of study medication and had a baseline and at least one post-baseline assessment for both primary efficacy measures.

Arm/Group Title	Cerebrolysin	0.9% Saline Solution
Arm/Group Description
Measure Participants	117	115
Mean (Standard Deviation) [points on a scale]	-10.60 (7.77)	-4.49 (8.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cerebrolysin, 0.9% Saline Solution
	Comments	The null-hypothesis stated no difference between the two treatment groups. A sample size of 103 evaluable patients per treatment group was estimated to allow for the detection of a significant group difference of 4.1 points in ADAS-cog+ weak 24 change score (standard deviation [SD] 9.0) in favor of Cerebrolysin with a power of 90% and a probability level of alpha-level 0.025 (one-sided).
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value obtained from the F-test statistic of Cerebrolysin versus Placebo as part of ANCOVA (analysis of covariance). No adjustment for multiple comparisons was needed. The overall significance level alpha was fixed at alpha = 0.05 (two-sided).
	Method	ANCOVA
	Comments	The study was designed to show significant differences in each of the two primary variables. No adjustment for multiple comparisons was needed.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.17
	Confidence Interval	(2-Sided) 95%; -8.22 to -4.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	CIBIC+ (Clinicians Interview-based Impression of Change) Score at Week 24
Description	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).
Time Frame	week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cerebrolysin	0.9% Saline Solution
Arm/Group Description
Measure Participants	117	115
Marked improvement	7 5.8%	2 1.7%
Moderate improvement	43 35.5%	14 11.6%
Minimal improvement	38 31.4%	27 22.3%
No change	20 16.5%	52 43%
Minimal worsening	9 7.4%	16 13.2%
Moderate worsening	0 0%	4 3.3%
Marked worsening	0 0%	0 0%

3. Secondary Outcome

Title	Change From Baseline in ADAS-COG+ (Alzheimer's Disease Assessment Scale Cognitive Subpart)
Description	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.
Time Frame	week 4, 12, 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	ADAS-COG+ Response
Description	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.
Time Frame	week 4, 12, 16, 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Change From Baseline for Original ADAS-COG
Description	The Original Alzheimer's Disease Assessment Scale - Cognitive (ADAS-COG) is comprised of items 1-11 of the modified ADAS-COG+.
Time Frame	week 4, 12, 16, 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	CIBIC+ Score
Description	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.
Time Frame	week 4, 12, 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	CIBIC+ Response
Description	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.
Time Frame	week 4, 12, 16, 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	CIBIS+ (Clinicians Interview-Based Impression of Severity)
Description	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.
Time Frame	week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Change From Baseline in MMSE (Mini-Mental State Examination) Score
Description	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.
Time Frame	week 4, 12, 16, 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Change From Baseline in ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale)
Description	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.
Time Frame	week 4, 12, 16, 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Change From Baseline in Trail-making Test
Description	The Trail-making test is a frequently used instrument for the assessment of executive function.
Time Frame	week 4, 12, 16, 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Change From Baseline in Clock-drawing Test
Description	The Clock-drawing test is a frequently used screening instrument for dementia drug studies. It evaluates executive function of demented patients.
Time Frame	week 4, 12, 16, 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Secondary Outcome

Title	Combined Response, i.e. Response in ADAS-COG+ and CIBIC+
Time Frame	week 4, 12, 16, 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Cerebrolysin		0.9% Saline Solution
Arm/Group Description
All Cause Mortality
	Cerebrolysin		0.9% Saline Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cerebrolysin		0.9% Saline Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/ (NaN)		0/ (NaN)
Infections and infestations
Pyelonephritis acute	1/117 (0.9%)	1	0/115 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	1/117 (0.9%)	1	0/115 (0%)	0
Rectosigmoid cancer	1/117 (0.9%)	1	0/115 (0%)	0
Other (Not Including Serious) Adverse Events
	Cerebrolysin		0.9% Saline Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/117 (0%)		0/115 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.