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.
Endogenous neurotrophic factors, also called neurotrophins, are signaling molecules in various cellular pathways and allow proper neuronal function, survival and regeneration. Sufficient supply is therefore regarded as a pre-requisite for neuronal maintenance but sudden or chronic pathological changes result in an imbalance of this regulatory system. Cerebrolysin is a peptide preparation acting in a similar way like endogenous neurotrophic factors. Due to its pleiotropic effects - neuroprotection, neuronal survival, neuroplasticity and neurogenesis -, Cerebrolysin is regarded as potential therapeutic tool in complex diseases like stroke or dementia. In contrast to naturally occurring neurotrophic factors, neuropeptides of Cerebrolysin enter the brain parenchyma by crossing the blood-brain barrier after peripheral (intravenous \[IV\]) administration. Another treatment approach for Alzheimer's disease targets the cholinergic system to increase cortical acetylcholine. One of these drugs is the anticholinesterase donepezil (Aricept). However, anticholinesterases seem to provide only symptomatic benefit for a limited period and not to influence the progression of the disease. In view of the different mechanisms of action and clinical profile of Cerebrolysin and Aricept, a combination therapy of both may provide synergistic treatment effects. The combination of a treatment targeting the neurotrophic axis (Cerebrolysin) with a treatment to improve cholinergic neurotransmission (Aricept) can arguably be expected to provide additional benefits to AD patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
217
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.
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).
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.
EuroEspes Biomedical Research Centre
A Coruña, Spain
Centro Geriátrico Fuente Salinas
Granada, Spain
Clínica de Memoria
Málaga, Spain
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.
Time frame: baseline and week 28
Clinical Interview-based Impression of Change (CIBIC+) Score
Time frame: week 28
Change From Baseline for ADAS-COG+
Time frame: week 4, 12, 16
ADAS-COG+ Responders
Time frame: week 4, 12, 16, 28
Change From Baseline for Original ADAS-COG
Time frame: week 4, 12, 16, 28
CIBIC+ Score
Time frame: week 4, 12, 16
CIBIC+ Responders
Time frame: week 4, 12, 16, 28
Clinical Interview-based Impression of Severity (CIBIS+) Score
Time frame: week 28
Change From Baseline for Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL)
Time frame: week 16, 28
Change From Baseline in Total Score for Neuropsychiatric Inventory (NPI)
Time frame: week 16, 28
Combined Responders, i.e. Response in ADAS-COG+ and CIBIC+
Time frame: week 4, 12, 16, 28
Adverse Experiences, Vital Signs, Physical and Neurological Examinations, Laboratory Tests (Hematology, Clinical Chemistry , Urinalysis, Electrocardiogram [ECG])
Time frame: Baseline, week 4, 12, 16, 28
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