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

February 10, 2020 updated by: First Affiliated Hospital Xi'an Jiaotong University

DL-3-n-butylphthalide Treatment in Patients With Mild to Moderate Alzheimer's Disease Already Receiving Donepezil : A Multi Center, Prospective Cohort Stud

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
92

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shaanxi
      • Xi'an, Shaanxi, China, 710061
        • First Affiliated Hospital of Xi'an JiaoTong University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

46 years to 81 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

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

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
the patients with mild to moderate AD have already been prescribed the drugs,we just observed passively.
Other Names:
  • NBP
Drug: Donepezil
the patients with mild to moderate AD have already been prescribed the drugs,we just observed passively.
Other Names:
  • Aricept
donepezil group
only using donepezil treatment in patients with mild to moderate AD
Drug: Donepezil
the patients with mild to moderate AD have already been prescribed the drugs,we just observed passively.
Other Names:
  • Aricept

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog)
Time Frame: Baseline, 48 weeks
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus)
Time Frame: Baseline, 48 weeks
secondary efficacy parameter is the endpoint score on CIBIC-plus
Baseline, 48 weeks
Alzheimer's Disease Cooperative Study-Activities of Daily Living(ADCS-ADL)
Time Frame: Baseline, 48 weeks
Secondary efficacy parameter is the baseline-to-endpoint score change on the ADCS-ADL.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 ADCS-ADL at last.
Baseline, 48 weeks
Neuropsychiatric Inventory(NPI)
Time Frame: Baseline, 48 weeks
Additional parameter included the baseline-to-endpoint score changes on the NPI.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 NPI at last.
Baseline, 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
First Affiliated Hospital Xi'an Jiaotong University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: qiu-min Qu, First Affiliated Hospital Xi'an Jiaotong University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 14, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 14, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 17, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 12, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 10, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • XJTU1AF-CRF-2015-027

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings