Efficacy of benfotiamine plus donepezil treatment for patients with mild‐to‐moderate Alzheimer’s disease: multicenter, randomized, phase II clinical trial

Abstract

AbstractBackgroundTo assess the efficacy of benfotiamine plus donepezil treating mild‐to‐moderate Alzheimer’s disease (AD).MethodDesign: Multicenter, randomised, double‐blind, phase II clinical trial. Setting: 21 cognitive clinics of tertiary hospitals affiliated Medical Colleges or Universities in China. Participants: 434 patients who took donepezil (5 mg daily) continuously for more than 6 months (inclusive) were screened. Intervention: 302 patients entered this study and were randomly assigned (1:1:1 allocation) to high‐dose benfotiamine (600 mg daily, n = 99) plus donepezil (5 mg daily, the same below), low‐dose benfotiamine (300 mg daily, n = 104) plus donepezil or the only donepezil (n = 99) groups. Main outcomes measures: The primary efficacy outcome was the change of Assessment Scale‐Cognitive Subscale 11(ADAS‐cog) score at week 52 from baseline.ResultIn the overall population, the primary efficacy outcome did not reach significant difference, but tended to be beneficial to benfotiamine plus donepezil treatment with a dose‐effect relationship. Post hoc analyses showed that for the moderate AD subgroup in the full analysis set, the increases of ADAS‐cog scores at week 52 from baseline were the least in high‐dose benfotiamine plus donepezil (‐3.07, p = 0.027) and the second least in low‐dose benfotiamine plus donepezil (‐1.49, p > 0.05) as compared with that in only donepezil. There were no significant differences in the primary efficacy outcome among three subgroups of mild cases.ConclusionCompared to only donepezil, benfotiamine plus donepezil treatment tends to have beneficial effects on delaying cognitive decline of mild to moderate AD. Post hoc analyses showed that the efficacy of benfotiamine plus donepezil treatment with a dose‐effect relationship is better than that of only donepezil treatment for moderate AD, but not for mild AD. The current proof of concept study showed that the combination treatment of correcting TDP reduction with acetylcholinesterase inhibitor is an effective therapeutic way for AD. Future studies should further expand the sample to verify these results.