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This is a 48-week, double-blind, randomized, placebo-controlled study. Sixty-four patients are randomly assigned to take NBP (600mg per day) or placebo for 48 weeks, with 32 patients in each treatment group. Anti-dementia treatment-naive patients meet the inclusion/exclusion criteria are enrolled.
Patients are assigned to NBP will take 200mg tid daily. Patients are visited at baseline, as well as 4, 12, 24, 36, 48weeks after baseline. Safety data is recorded until an additional 30 days after the last treatment (48 weeks).
The primary outcomes include cognitive function and activities of daily living (ADL). All subjects are assessed at baseline, 4w, 12w,24w, 36w intermittent visit and 48w endpoint with the Auditory Verbal Learning Test (AVLT), the Brief Visuospatial Memory Test-Revised (BVMT-R), the Symbol Digit Modalities Test (SDMT), the Trail Making Test-A/B (TMT-A/B), the Benton Judgment of Line Orientation (JLO), the verbal fluency test, the Boston Naming Test (BNT), the Controlled Oral Word Association Test (COWAT), the Stroop test, the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and the ADL. The secondary outcomes include the global function and behavioral and psychological symptoms of dementia (BPSD), which are evaluated with the Clinical Dementia Rating (CDR) and the Neuropsychiatric Inventory (NPI), respectively. Independent raters who are blinded to patients' distribution are assigned to assess the participants.
The exploratory outcomes are markers of vascular regulation, including circulating endothelial progenitor cells (EPCs), white matter hyperintensities (WMH) on MRI, cerebral blood flow (CBF) measured with transcranial Doppler (TCD) and arterial spin labeling (ASL) MRI, and parameters of carotid duplex ultrasonic (CDU). In addition, apolipoprotein E (APOE) polymorphism and plasma biomarkers are also detected.
Safety are assessed at each visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NBP | Experimental | DL-3-n-butylphthalide (NBP), soft capsule, 200mg Tid, po, for 48 weeks. |
|
| Placebos | Placebo Comparator | Placebo, soft capsule, 200mg Tid, po, for 48 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NBP | Drug | NBP soft capsules |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Auditory Verbal Learning Test (AVLT) at endpoint and change from baseline | AVLT is used to evaluate verbal learning and memory ability. Higher score indicates better performance. | 48 weeks post-dose and change from baseline |
| Brief Visuospatial Memory Test-Revised (BVMT-R) at endpoint and change from baseline | BVMT-R is used to evaluate spatial memory ability. Higher score indicates better performance. | 48 weeks post-dose and change from baseline |
| Digital span (DS) at endpoint and change from baseline | DS is used to assess attention. Higher score indicates better performance. | 48 weeks post-dose and change from baseline |
| Symbol Digit Modalities Test (SDMT) at endpoint and change from baseline | SDMT is used to assess information processing speed. Higher score indicates better performance. | 48 weeks post-dose and change from baseline |
| Trail Making Test-A (TMT-A) at endpoint and change from baseline | TMT-A is used to assess information processing speed. Lower score indicates better performance. | 48 weeks post-dose and change from baseline |
| TMT-B at endpoint and change from baseline | TMT-B is used to assess executive function. Lower score indicates better performance. | 48 weeks post-dose and change from baseline |
| Stroop test at endpoint and change from baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Global function at endpoint and change from baseline | Clinical Dementia Rating (CDR) is used to evaluate global function. | 48 weeks post-dose and change from baseline |
| Neuropsychiatric Inventory (NPI) at endpoint and change from baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Hamilton Depression Scale (HAMD) at endpoint and change from baseline | HAMD is used to evaluate depressive symptoms. | 48 weeks post-dose and change from baseline |
| Geriatric Depression Scale (GDS) at endpoint and change from baseline |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Nan Zhang, MD, PhD | Contact | +8622 60119688 | nkzhangnan@163.com | |
| Mengya Xing, MD, PhD | Contact | +86 13702198695 | xing_mengya@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Nan Zhang, MD, PhD | Tianjin Medical University General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tianjin Medicial University General Hospital | Recruiting | Tianjin | Tianjin Municipality | 300052 | China |
De-identified individual participant data for all primary and secondary outcome measures will be available
Data will be available within 6 months of study completion.
Data access requests will be reviewed by an external Independent Review Panel. Requestors will be required to sign a Data Access Agreement.
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| ID | Term |
|---|---|
| D015140 | Dementia, Vascular |
| D059345 | Cerebral Small Vessel Diseases |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C027125 | 3-n-butylphthalide |
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double-blind, randomized, placebo controlled study
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| Placebos | Drug | Soft capsules manufactured to mimic NBP |
|
Stroop test is used to assess executive function. Higher score indicates better performance. |
| 48 weeks post-dose and change from baseline |
| Benton Judgment of Line Orientation (JLO) at endpoint and change from baseline | JLO is used to assess visuospatial function. Higher score indicates better performance. | 48 weeks post-dose and change from baseline |
| Verbal fluency test at endpoint and change from baseline | Verbal fluency test is used to evaluate language function. Higher score indicates better performance. | 48 weeks post-dose and change from baseline |
| Boston Naming Test (BNT) at endpoint and change from baseline | BNT is used to evaluate language function. Higher score indicates better performance. | 48 weeks post-dose and change from baseline |
| Controlled Oral Word Association Test (COWAT) at endpoint and change from baseline | COWAT is used to evaluate language function. Higher score indicates better performance. | 48 weeks post-dose and change from baseline |
| Mini-Mental State Examination (MMSE) at endpoint and change from baseline | MMSE is used to evaluate global cognition. Higher score indicates better performance. | 48 weeks post-dose and change from baseline |
| Montreal Cognitive Assessment (MoCA) at endpoint and change from baseline | MoCA is used to evaluate global cognition. Higher score indicates better performance. | 48 weeks post-dose and change from baseline |
| Activity of daily living (ADL) at endpoint and change from baseline | ADL is used to evaluate activities of daily living. | 48 weeks post-dose and change from baseline |
NPI is used to evaluate behavioral and psychological symptoms of dementia (BPSD).
| 48 weeks post-dose and change from baseline |
GDS is used to evaluate depressive symptoms.
| 48 weeks post-dose and change from baseline |
| Regulation of endothelial progenitor cell at endpoint and change from baseline | Circulating endothelial progenitor cell (EPC) is detected with flow cytometry. | 48 weeks post-dose and change from baseline |
| Transcranial Doppler (TCD) at endpoint and change from baseline | TCD is used to measure cerebral blood flow. | 48 weeks post-dose and change from baseline |
| Carotid duplex ultrasonic (CDU) at endpoint and change from baseline | CDU is used to evaluate cerebral blood flow and arteriosclerosis. | 48 weeks post-dose and change from baseline |
| Arterial spin labeling (ASL) MRI at endpoint and change from baseline | Arterial spin labeling (ASL) is used to measure cerebral blood flow. | 48 weeks post-dose and change from baseline |
| White matter hyperintensities (WMH) at endpoint and change from baseline | The extent and volume of WMH are analyzed on MRI. | 48 weeks post-dose and change from baseline |
| D002537 | Intracranial Arteriosclerosis |
| D020765 | Intracranial Arterial Diseases |
| D003704 | Dementia |
| D056784 | Leukoencephalopathies |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |