Alzheimer's DiseaseNCT02711683
DL-3-n-butylphthalide Treatment in Patients With Mild to Moderate Alzheimer's Disease Already Receiving Donepezil
An observational study of Alzheimer's Disease, run by First Affiliated Hospital Xi'an Jiaotong University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- DL-3-n-butylphthalide and Donepezil
- How many people
- 92 participants
- Where
- 1 siteChina
- Study dates
- Mar 2016to Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients With Mild to Moderate Alzheimer's Disease Already Receiving Donepezil
Who may be able to join
- 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.
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- absent of neurological sign;
- having used donepezil more than 3 months and remained relatively stable；
- sign the informed consent.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, 710061
About this study
Official title: 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.
- Conditions
- Alzheimer's Disease
- Being tested
- DL-3-n-butylphthalide, Donepezil
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DL-3-n-butylphthalideDrug
Also called NBP
the patients with mild to moderate AD have already been prescribed the drugs,we just observed passively.
DonepezilDrug
Also called Aricept
the patients with mild to moderate AD have already been prescribed the drugs,we just observed passively.
| Study group | Role | What they receive |
|---|---|---|
| DL-3-n-butylphthalide group | using DL-3-n-butylphthalide treatment in patients with mild to moderate AD already receiving donepezil Receives: Drug: DL-3-n-butylphthalide; Drug: Donepezil | |
| donepezil group | only using donepezil treatment in patients with mild to moderate AD Receives: Drug: Donepezil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 48 weeks
Secondary outcomes (3)
Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus)
secondary efficacy parameter is the endpoint score on CIBIC-plus
Measured: Baseline, 48 weeks
Alzheimer's Disease Cooperative Study-Activities of Daily Living(ADCS-ADL)
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.
Measured: Baseline, 48 weeks
Neuropsychiatric Inventory(NPI)
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.
Measured: Baseline, 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2016 (estimated)
- Study startMar 2016
- Primary completionDec 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by First Affiliated Hospital Xi'an Jiaotong UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- qiu-min Qu, Study director, First Affiliated Hospital Xi'an Jiaotong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02711683
- Sponsor's protocol ID
- XJTU1AF-CRF-2015-027
- Status last verified
- Jan 2020
- First submitted
- 14 Mar 2016
- Last updated
- 12 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DL-3-n-butylphthalide Treatment in Patients With Mild to Moderate Alzheimer's Disease Already Receiving Donepezil : A Multi Center, Prospective Cohort Stud
- ClinicalTrials.gov ID
- NCT02711683
- Acronym / sponsor ID
- XJTU1AF-CRF-2015-027
- Conditions
- Alzheimer's Disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- First Affiliated Hospital Xi'an Jiaotong UniversityUniversity, hospital or other
- Study start
- Mar 2016 (actual)
- Primary completion
- Dec 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 17 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DL-3-n-butylphthalide group | – | Drug: DL-3-n-butylphthalide, Drug: Donepezilusing DL-3-n-butylphthalide treatment in patients with mild to moderate AD already receiving donepezil |
| donepezil group | – | Drug: Donepezilonly using donepezil treatment in patients with mild to moderate AD |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients With Mild to Moderate Alzheimer's Disease Already Receiving Donepezil
Key inclusion criteria (9 listed)
- 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;
Key exclusion criteria (7 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DL-3-n-butylphthalideAlso: NBPthe patients with mild to moderate AD have already been prescribed the drugs,we just observed passively. | Drug | DL-3-n-butylphthalide group |
| DonepezilAlso: Ariceptthe patients with mild to moderate AD have already been prescribed the drugs,we just observed passively. | Drug | DL-3-n-butylphthalide group, donepezil group |
Primary outcome
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.
3 secondary outcomes
Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus)
Time frame: Baseline, 48 weeks
Alzheimer's Disease Cooperative Study-Activities of Daily Living(ADCS-ADL)
Time frame: Baseline, 48 weeks
Neuropsychiatric Inventory(NPI)
Time frame: Baseline, 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2020.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
qiu-min Qu study director
First Affiliated Hospital Xi'an Jiaotong University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Alzheimer's Disease, run by First Affiliated Hospital Xi'an Jiaotong University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) (time frame: Baseline, 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2020.