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)
Overview
- Phase
- Phase 2
- Intervention
- Cerebrolysin + donepezil
- Conditions
- Alzheimer Disease
- Sponsor
- Ever Neuro Pharma GmbH
- Enrollment
- 217
- Locations
- 3
- Primary Endpoint
- Change From Baseline in Alzheimer's Disease Assessment Scale Cognitive Subpart (Extended Version) (ADAS-COG+) at Week 28
- Status
- Completed
- Last Updated
- 16 years ago
Overview
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Cerebrolysin + donepezil
Intervention: Cerebrolysin + donepezil
Cerebrolysin + placebo
Intervention: Cerebrolysin + placebo
Donepezil + placebo
Intervention: Donepezil + placebo
Outcomes
Primary Outcomes
Change From Baseline in Alzheimer's Disease Assessment Scale Cognitive Subpart (Extended Version) (ADAS-COG+) at Week 28
Time Frame: baseline and 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.
Clinical Interview-based Impression of Change (CIBIC+) Score
Time Frame: week 28
Secondary Outcomes
- 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)
- Clinical Interview-based Impression of Severity (CIBIS+) Score(week 28)
- Change From Baseline for Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL)(week 16, 28)
- Change From Baseline in Total Score for Neuropsychiatric Inventory (NPI)(week 16, 28)
- Combined Responders, i.e. Response in ADAS-COG+ and CIBIC+(week 4, 12, 16, 28)
- Adverse Experiences, Vital Signs, Physical and Neurological Examinations, Laboratory Tests (Hematology, Clinical Chemistry , Urinalysis, Electrocardiogram [ECG])(Baseline, week 4, 12, 16, 28)