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

NCT00911807 | Completed Phase 2 Results

• 1 other identifier: EBE-031010
• Study Type: interventional
• Target: 217
• Locations: 1 country
• Sites: 3

Brief Summary

The study was performed to compare the safety and efficacy of Cerebrolysin (10 mililiters \[ml\]), Aricept (10 miligrams \[mg\]), and a combination of both treatments on cognitive performance and global function in patients with probable Alzheimer's Disease (AD). It should also be assessed if the treatments have a positive effect on activities of daily living and neuropsychiatric symptoms. Oral treatment with Aricept or Placebo was given once daily throughout the study. Intravenous treatment with Cerebrolysin or Placebo was given once daily for 5 days per week during week 1 to 4 and during week 13 to 16 of the study. During the study patients had six visits at the hospital for evaluation.

Conditions

Alzheimer Disease

Keywords

Clinical Trial, Phase II; Randomized Controlled Trial; Multicenter Study; Cerebrolysin; Donepezil

Outcome Measures

Primary Outcomes (2)

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

  The ADAS-cog+ is a validated, widely used, 14 item psychometric instrument for testing cognitive functions with increased sensitivity in detecting changes in milder patients compared to the original ADAS-cog. It has a maximum score of 85 with a higher score indicating impairment and was assessed by a qualified neuropsychologist.

  baseline and week 28

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

  week 28

Secondary Outcomes (10)

• Change From Baseline for ADAS-COG+

  week 4, 12, 16

• ADAS-COG+ Responders

  week 4, 12, 16, 28

• Change From Baseline for Original ADAS-COG

  week 4, 12, 16, 28

• CIBIC+ Score

  week 4, 12, 16

• CIBIC+ Responders

  week 4, 12, 16, 28

Study Arms (3)

Cerebrolysin + donepezil

EXPERIMENTAL

Drug: Cerebrolysin + donepezil

Cerebrolysin + placebo

EXPERIMENTAL

Drug: Cerebrolysin + placebo

Donepezil + placebo

ACTIVE COMPARATOR

Drug: Donepezil + placebo

Interventions

Cerebrolysin + donepezil DRUG

Cerebrolysin (10 ml) was given as IV infusion on five days per week for four consecutive weeks (week 1-4) with repetition of this treatment course (week 13-16) after a two-months treatment free interval, accounting for a total of 40 infusions. Donepezil was given PO once daily during the whole study duration (28 weeks). After four weeks the daily dosage was increased from 5 mg to 10 mg.

Also known as: Brand name for donepezil: Aricept, Brand name for Cerebrolysin: Cerebrolysin

Cerebrolysin + donepezil

Cerebrolysin + placebo DRUG

Cerebrolysin (10 ml) was given as IV infusion on five days per week for four consecutive weeks (week 1-4) with repetition of this treatment course (week 13-16) after a two-months treatment free interval, accounting for a total of 40 infusions. Placebo for donepezil was given PO once daily during the whole study duration (28 weeks).

Also known as: Brand name for Cerebrolysin: Cerebrolysin

Cerebrolysin + placebo

Donepezil + placebo DRUG

Placebo for Cerebrolysin was given as IV infusion on five days per week for four consecutive weeks (week 1-4) with repetition of this treatment course (week 13-16) after a two-months treatment free interval, accounting for a total of 40 infusions. Donepezil was given PO once daily during the whole study duration (28 weeks). After four weeks the daily dosage was increased from 5 mg to 10 mg.

Also known as: Brand name for donepezil: Aricept

Donepezil + placebo

Eligibility Criteria

• Age: 51 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Ever Neuro Pharma GmbH: lead
• acromion GmbH: collaborator

Study Sites (3)

EuroEspes Biomedical Research Centre

A Coruña, 15166, Spain

Location

Centro Geriátrico Fuente Salinas

Granada, 18340, Spain

Location

Clínica de Memoria

Málaga, 29005, Spain

Location

Related Publications (1)

• 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.

  PMID: 21679156 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

cerebrolysin; Donepezil

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Philipp Novak
• Organization: EBEWE Pharma

philipp.novak@ebewe.com

01143-7665-8123

Study Officials

• Ánton X Àlvarez, MD, PhD

  EuroEspes Biomedical Research Center

  PRINCIPAL INVESTIGATOR

• Herbert Moessler, PhD

  EBEWE Pharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 7, 2009
• First Posted: June 2, 2009
• Study Start: October 1, 2004
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: June 10, 2009
• Results First Posted: June 2, 2009

Record last verified: 2009-06

Locations

ES (3)