Combined treatment with cerebrolysin and donepezil in mild to moderate alzheimer's disease: Results of a double-blind, randomized clinical trial

Background: Cerebrolysin (Cere) is a peptide mixture with neurotrophic activity being effective in Alzheimer's disease (AD) treatment. A randomized, double-blind clinical trial was conducted to evaluate the efficacy and the safety of Cere, Donepezil and a combination therapy in mild to moderate AD patients. Methods: AD patients (N=197 45 male/152 female; age: 51-95 years) received iv infusions of Cere (10 ml) or placebo (saline) 5 days/week from weeks 1-4 and 13-16 (40 infusions) and Donepezil (5 mg for 4 weeks and 10 mg thereafter) or placebo tablets throughout the study. The effects of Cere, Donepezil and Combination on cognition, clinical global impression, activities of daily living and neuropsychiatric symptoms were evaluated with ADAS-cog, CIBIC+, ADCS-ADL and NPI. Primary efficacy parameters were CIBIC+ score and change from baseline in the ADAS-cog+ at week 28. Results: At week 28 and in comparison with patients treated only with Donepezil: (1) Cere-treated patients showed a significant improvement in global clinical impression (CIBIC+: p<0.05; CIBIC+ responders rate: p<0.01) and no significant differences for ADAScog, ADCS-ADL and NPI scores; (2) patients receiving combination therapy showed higher scores in the CIBIC+ responders rate (p<0.01), almost significant differences in CIBIC+ score (p=0.068) and ADAS-cog&CIBIC+ responders rate (p=0,056), and nonsignificant improvements in ADAS-cog and ADCS-ADL. Patients treated with Cere or Combination were cognitively stable and those receiving only Donepezil deteriorated after week 16. Conclusions: Results of the present study indicate that: 1) Cere is at least as efficacious as Donepezil for the treatment of mild-moderate AD; 2) The combined therapy showed a tendency for superiority with respect to Donepezil alone. Since Cere-treated patients maintained cognitive improvement till the end of the study and those receiving only Donepezil deteriorated after week 16, long-term benefits of the combination therapy with Cere+Donepezil are suggested and must be investigated in future clinical trials.