DL-3-n-butylphthalide Treatment in Patients With Mild to Moderate Alzheimer's Disease Already Receiving Donepezil
Status:
Completed
Trial end date:
2019-12-01
Target enrollment:
Participant gender:
Summary
Alzheimer's disease (AD) is the commonest cause of dementia. There is no effective treatment
to cure the disease. Cholinesterase inhibitors, such as donepezil, are widely recommended to
patients with mild to moderate AD. But the cognitive function of most of the patients using
donepezil gradually aggravate, with Mini-Mental State Examination(MMSE) score falling by 2
points per year on average, and donepezil cannot effectively delay AD progress.
DL-3-n-butylphthalide(NBP) is a synthetic chiral compound containing L- and D-isomers of
butylphthalide. It is developed from L-3-n-butylphthalide, which was initially isolated as a
pure component from seeds of Apium graveolens in 1978 by researchers of Institute of Medicine
of Chinese Academy of Medical Sciences. Studies in the past several decades have demonstrated
that NBP is effective in alleviating oxidative damage and mitochondria dysfunction, improving
microcirculation. NBP was approved by the State Food and Drug Administration of China (SFDA)
as a therapeutic drug for treatment of ischemic stroke in 2005 Not only for ischemic stroke,
NBP has been reported to increase the expression of N-methyl-D-aspartate subtype glutamate
receptor 2B(NR2B) and synaptophysin in hippocampus of aged rats after chronic cerebral
hypoperfusion and increasing brain acetylcholine level, which are important processes
involved in learning and memory. It could alleviate the learning and memory deficits induced
by cerebral ischemia in rats. A multicentre, randomized, double-blind, placebo-controlled
trial conducted by Professor Jia investigated that NBP was effective for improving cognitive
and global functioning in patients with subcortical vascular cognitive impairment without
dementia and exhibited good safety over the 6-month treatment period. The pathogenesis of AD
involved mitochondria dysfunction and microcirculation dysfunction, which are the action
targets of NBP. Investigators observed that MMSE score lowering slowly when using NBP
treatment in patients with mild to moderate AD already receiving donepezil. But investigators
lack of system evaluation and follow-up. Hence, investigators hypothesized that NBP may have
therapeutic efficacy for patients with AD and designed the present study.
Details
Lead Sponsor:
First Affiliated Hospital Xi'an Jiaotong University