DL-3-n-butylphthalide Treatment in Patients With Mild to Moderate Alzheimer's Disease Already Receiving Donepezil

NCT02711683 | Completed

• 1 other identifier: XJTU1AF-CRF-2015-027
• Study Type: observational
• Target: 92
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog)

  Primary efficacy parameter is the baseline- to-endpoint score change on ADAS-cog. The participants will be followed up every 12 weeks. There is five times interviews totally. The investigators compare the the baseline- to-endpoint score change on ADAS-cog at last.

  Baseline, 48 weeks

Secondary Outcomes (3)

• Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus)

  Baseline, 48 weeks

• Alzheimer's Disease Cooperative Study-Activities of Daily Living(ADCS-ADL)

  Baseline, 48 weeks

• Neuropsychiatric Inventory(NPI)

  Baseline, 48 weeks

Study Arms (2)

DL-3-n-butylphthalide group

using DL-3-n-butylphthalide treatment in patients with mild to moderate AD already receiving donepezil

Drug: DL-3-n-butylphthalide; Drug: Donepezil

donepezil group

only using donepezil treatment in patients with mild to moderate AD

Drug: Donepezil

Interventions

DL-3-n-butylphthalide DRUG

the patients with mild to moderate AD have already been prescribed the drugs,we just observed passively.

Also known as: NBP

DL-3-n-butylphthalide group

Donepezil DRUG

the patients with mild to moderate AD have already been prescribed the drugs,we just observed passively.

Also known as: Aricept

DL-3-n-butylphthalide group; donepezil group

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients With Mild to Moderate Alzheimer's Disease Already Receiving Donepezil

You may qualify if:

• literate Chinese, aged 50-85 years, with a consistent caregiver who accompanied the subjects at least 4 days a week，2 hours a day;
• complaint and/or informant report of cognitive impairment involving memory and/or other cognitive domains lasting for at least 12 months; and progressing gradually.
• diagnosis of probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria;
• a mini-mental state examination (MMSE) score ≥11 and ≤22 (primary school) or ≥11 and ≤26 (junior school or above) ;
• Hachinski ischemia scale score ≤4;
• All patients meeting the clinical criteria underwent brain magnetic resonance imaging (MRI) scan including hippocampal assessment at screening. The MRI entry criteria are as follows: the number of cerebral infarcts (≥20 mm in diameter)less than 2, without infarcts in thalamus, hippocampal or entorhinal cortex, the medial temporal lobe atrophy visual rating scale (MTA) score more than 2 degree.
• absent of neurological sign;
• having used donepezil more than 3 months and remained relatively stable；
• sign the informed consent.

You may not qualify if:

• severe white matter lesion(WML)(score ≥3 according to the Fazekas rating scale), the number of cerebral infarcts (≥20 mm in diameter)more than 2, with infarcts in the important sites, such as thalamus, hippocampal or entorhinal cortex;
• dementia due to other causes, such as vascular dementia, infection of central nervous system，dementia with Lewy body(DLB)，etc
• suffered from other neurological disease, such as stroke, Parkinson's disease, epilepsy；
• suffered from mental disorders, such as schizophrenia，bipolar disorder，severe depression, delirium;
• suffered from unstable or severe disorders of heart, lung, liver, kidney and blood system;
• Severe impairment of vision and hearing;
• Using other cholinesterase inhibitors or memantine.

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead

Study Sites (1)

First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

3-n-butylphthalide; Donepezil

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Study Officials

• qiu-min Qu

  First Affiliated Hospital Xi'an Jiaotong University

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2016
• First Posted: March 17, 2016
• Study Start: March 1, 2016
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: February 12, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)