Combi

CompletedPhase 2Results posted

Comparative Study to Test Safety and Efficacy of Neurotrophic and Cholinergic Treatment of Alzheimer's Disease

A Randomized, Double-Blind, Clinical Trial to Compare the Safety and Efficacy of Cerebrolysin and Aricept (Donepezil) and a Combination Therapy in Patients With Probable Alzheimer's Disease (AD)

Lead sponsor

Ever Neuro Pharma GmbH

Assets

Cerebrolysin + donepezil / Donepezil

Listed sites

Recruiting sites

Enrollment

217

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 12-25

Primary endpoints

•ADAS-Cog•Clinical Interview-based Impression of Change (CIBIC+) Score

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDEBE-031010

NCT IDNCT00911807

Timeline

Milestones

Study start2004-10 (month precision)

Primary completion2008-04actual (month precision)

Study completion2008-04actual (month precision)

Study first posted2009-06-02estimated

Results first posted2009-06-02estimated

Last update posted2009-06-10estimated

Assets

Drug assets

Cerebrolysin + donepezil Donepezil

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age51 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Diagnosis of probable AD (Diagnostic and Statistical Manual of Mental Disorders, 4th revision [DSM-IV], National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association [NINCDS-ADRDA])

•Mini-Mental-State-Examination (MMSE) of 12-25, inclusive

•Modified Hachinski score ≤4

•Computed tomography (CT) or magnetic resonance imaging (MRI) scan within 12 months prior to screening without evidence of infection, infarction, or other focal lesions and without clinical symptoms suggestive of intervening neurological disease. Patients who have had a single, clinically silent lacunar infarct are eligible provided the lacunar infarct is not felt to be responsible for the patient's symptoms, is <1 centimeter (cm) maximal diameter in any dimension, is not present in hippocampus of either hemisphere, head of the left caudate, or the dorsomedial region of the left thalamus. Subjects with scans showing atrophy, ventricular enlargement or mild to moderate white matter changes (involving up to approximately 25% of hemispheric white matter) are eligible if the study is otherwise normal.

•Hamilton Depression Scale score of ≤15

•Adequate visual and auditory acuity to allow neuropsychological testing

•Ability to attempt all sections of the Alzheimer's Disease Assessment Scale Cognitive Subpart (extended version)(ADAS-cog+)

•Good general health without additional diseases expected to interfere with the study

•Normal B12, folic acid, venereal disease research laboratory (VDRL), and thyroid-stimulating hormone (TSH) or without any clinically significant laboratory abnormalities that would be expected to interfere with the study

•Electrocardiogram (ECG) and chest x-ray (if clinically necessary per Investigator) without clinically significant laboratory abnormalities that would be expected to interfere with the study

•Patient is not institutionalized

•Patient is not pregnant, lactating, or of childbearing potential

•Sufficient language skills to complete all testing without assistance of a language interpreter

•Responsible caregiver being present during administration of study drug, monitor the patient's compliance with study procedures and adverse events, and accompany the patient to all clinic visits

•Written informed consent obtained from the patient and caregiver prior to entry into the study

Exclusion criteria

•Any clinically significant laboratory abnormalities on the battery of screening tests

•Patients who in the past have not tolerated treatment with 10 mg Aricept or treatment with a corresponding dose of another cholinesterase inhibitor

•Severe psychotic features, depression, agitation or behavioral problems within the last three months that could lead to difficulty complying with the protocol

•Any significant systemic illness or unstable medical condition that could lead to difficulty complying with the protocol

•Patients who in the Investigator's opinion would not comply with study procedures

•Any significant neurological disease other than Alzheimer's Disease, within the past five years, or with residual effects

•Delusional symptoms are often characteristic of Alzheimer's Disease, but patients with symptoms so pronounced that they warrant an alternative diagnosis are excluded

•History of alcohol or substance abuse or dependence within the past two years (DSM-IV)

•History of schizophrenia (DSM-IV)

•Patients with a history of systemic cancer within the past two years are excluded

•History of myocardial infarction in the past year or unstable or severe cardiovascular disease, including uncontrolled hypertension

•Uncontrolled insulin-requiring diabetes or non-insulin dependent diabetes mellitus (Haemoglobin A1c [HBA1c] > 10.0)

•Use of:

-systemic corticosteroids for more than one week within three months prior to Baseline (BL)

-Anti-Parkinsonian agents within two months prior to baseline (BL)

-Approved or investigational Cholinesterase Inhibitors within 30 days or five half-lives, whichever is longer, prior to BL

-Memantine or other N-methyl-D-aspartic acid (NMDA) antagonists within 30 days or five half-lives, whichever is longer, prior to BL

-Treatment with high potency neuroleptics or narcotic analgesics within four weeks prior to BL

-Cimetidine within four weeks prior to BL

-Sedatives more frequently than two times per week for sleep within four weeks prior to BL

Endpoints (24)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Other clinical outcomes

Function / daily living

Behavior / neuropsychiatric

Safety / tolerability / PK

Other (unclassified)

Global cognition

10 endpoints

Primary/protocol endpoint

Change From Baseline in Alzheimer's Disease Assessment Scale Cognitive Subpart (Extended Version) (ADAS-COG+) at Week 28

Time frame:baseline and week 28

ADAS-Cog

change from baseline, improvement

Primary/registry result

Change From Baseline in Alzheimer's Disease Assessment Scale Cognitive Subpart (Extended Version) (ADAS-COG+) at Week 28

Time frame:baseline and week 28

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), points on a scale	Standard deviation
Cerebrolysin + Donepeziln=67 Participants	-2.348	5.993
Cerebrolysinn=64 Participants	-1.711	7.500
Donepeziln=66 Participants	-1.246	6.147

Mean Square (Factor Treatment)19.59p0.6348ANCOVA

Mean Difference (Final Values)-0.63095% CI-2.891 - 1.630p0.5830t-test, 2 sided

Multiple testing of individual null hypotheses that control for the overall significance level alpha = 0.05 were performed by using the 'closed testing procedure'

Mean Difference (Final Values)-1.08095% CI-3.324 - 1.163p0.3434t-test, 2 sided

Multiple testing of individual null hypotheses that control for the overall significance level alpha = 0.05 were performed by using the 'closed testing procedure'.

Mean Difference (Final Values)-0.45095% CI-2.719 - 1.819p0.6962t-test, 2 sided

Multiple testing of individual null hypotheses that control for the overall significance level alpha = 0.05 were performed by using the 'closed testing procedure'.

Secondary/protocol endpoint

Change From Baseline for ADAS-COG+

Time frame:week 4, 12, 16

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

ADAS-COG+ Responders

Time frame:week 4, 12, 16, 28

ADAS-Cog

threshold achievement, improvement

Secondary/protocol endpoint

Change From Baseline for Original ADAS-COG

Time frame:week 4, 12, 16, 28

ADAS-Cog

change from baseline, improvement

Secondary/registry result

Change From Baseline for ADAS-COG+

Time frame:week 4, 12, 16

ADAS-Cog

change from baseline, improvement

Secondary/registry result

ADAS-COG+ Responders

Time frame:week 4, 12, 16, 28

ADAS-Cog

threshold achievement, improvement

Secondary/protocol endpoint

Combined Responders, i.e. Response in ADAS-COG+ and CIBIC+

Time frame:week 4, 12, 16, 28

ADAS-Cog

threshold achievement, improvement

Secondary/registry result

Change From Baseline for Original ADAS-COG

Time frame:week 4, 12, 16, 28

ADAS-Cog

change from baseline, improvement

Secondary/registry result

Combined Responders, i.e. Response in ADAS-COG+ and CIBIC+

Time frame:week 4, 12, 16, 28

ADAS-Cog

threshold achievement, improvement

Function / daily living

2 endpoints

Secondary/protocol endpoint

Change From Baseline for Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL)

Time frame:week 16, 28

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

Change From Baseline for Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL)

Time frame:week 16, 28

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Behavior / neuropsychiatric

2 endpoints

Secondary/protocol endpoint

Change From Baseline in Total Score for Neuropsychiatric Inventory (NPI)

Time frame:week 16, 28

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/registry result

Change From Baseline in Total Score for Neuropsychiatric Inventory (NPI)

Time frame:week 16, 28

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Safety / tolerability / PK

2 endpoints

Secondary/protocol endpoint

Adverse Experiences, Vital Signs, Physical and Neurological Examinations, Laboratory Tests (Hematology, Clinical Chemistry , Urinalysis, Electrocardiogram [ECG])

Time frame:Baseline, week 4, 12, 16, 28

descriptive

Secondary/registry result

Adverse Experiences, Vital Signs, Physical and Neurological Examinations, Laboratory Tests (Hematology, Clinical Chemistry , Urinalysis, Electrocardiogram [ECG])

Time frame:Baseline, week 4, 12, 16, 28

descriptive

Other clinical outcomes

6 endpoints

Primary/protocol endpoint

Clinical Interview-based Impression of Change (CIBIC+) Score

Time frame:week 28

descriptive

Primary/registry result

Clinical Interview-based Impression of Change (CIBIC+) Score

Time frame:week 28

descriptive

Secondary/protocol endpoint

CIBIC+ Score

Time frame:week 4, 12, 16

descriptive

Secondary/protocol endpoint

CIBIC+ Responders

Time frame:week 4, 12, 16, 28

threshold achievement, improvement

Secondary/registry result

CIBIC+ Score

Time frame:week 4, 12, 16

descriptive

Secondary/registry result

CIBIC+ Responders

Time frame:week 4, 12, 16, 28

threshold achievement, improvement

Other (unclassified)

2 endpoints

Secondary/protocol endpoint/low confidence

Clinical Interview-based Impression of Severity (CIBIS+) Score

Time frame:week 28

descriptive

Secondary/registry result/low confidence

Clinical Interview-based Impression of Severity (CIBIS+) Score

Time frame:week 28

descriptive

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Alvarez XA, Cacabelos R, Sampedro C, Couceiro V, Aleixandre M, Vargas M, Linares C, Granizo E, Garcia-Fantini M, Baurecht W, Doppler E, Moessler H. Combination treatment in Alzheimer's disease: results of a randomized, controlled trial with cerebrolysin and donepezil. Curr Alzheimer Res. 2011 Aug;8(5):583-91. doi: 10.2174/156720511796391863.
PMID21679156via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.