Clinical trial NCT03906123: The Efficacy of DL-NBP in Patients With Mild Subcortical Ischemic Vascular Dementia
Official title: The Efficacy of DL-3-n-butylphthalide (DL-NBP) on the Cognitive Function and Vascular Regulation in Patients With Mild Vascular Dementia (VaD) Caused by Subcortical Ischemic Vascular Disease (SIVD)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Subcortical Vascular Dementia
Cerebral Small Vessel Diseases
Keywords: DL-3-n-butylphthalide
vascular dementia
cerebral small vessel disease
cognitive function
cerebral blood flow
Lead sponsor: Tianjin Medical University General Hospital
Sponsor class: OTHER
First posted: 2019-04-08
Enrollment: 64
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: double-blind, randomized, placebo controlled study
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Patients meet the criteria of major neurocognitive disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5);
2. Patients aged with 50-80 years, years of education no less than 3, an MMSE range of 15\~26, an MoCA \< 26, an Hamilton Depression Scale (HAMD) \< 17;
3. The MRI (one research dedicated machine 3.0 T) features satisfy subcortical small vessel disease, including (1) multiple (\>=3) supratentorial subcortical lacunes (3-20 mm in diameter), with/without white matter hyperintensities (WMH) of any degree; (2) moderate to severe WMH (score\>= 2 according to the Fazekas rating scale in either periventricular region or deep white matter) with/without lacunes; (3) one or more strategically located subcortical small infarcts in the deep grey matters;
4. Patients or legal representative should sign the informed consent and have a reliable caregiver.

Exclusion Criteria:

1. Cognitive impairment caused by other central nervous system diseases, such as AD, dementia with Lewy body, frontal-temporal lobe degeneration, etc;
2. Cognitive impairment due to other conditions, such as severe depression, vitamin B 12 deficiency, abnormal thyroid function, etc;
3. Alcoholism, drug abuse or other conditions influenced the evaluation of cognition;
4. Patients unable to undertake MRI assessment.
5. Patients with a history of other severe disease such as epilepsy, myocardial infarction or heart failure will be excluded;
6. Administration of other investigational drugs, psychotropic drugs, drugs with psychiatric side effects, and oral anticoagulants are not allowed

Primary outcomes:
measure: Auditory Verbal Learning Test (AVLT) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Brief Visuospatial Memory Test-Revised (BVMT-R) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Digital span (DS) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Symbol Digit Modalities Test (SDMT) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Trail Making Test-A (TMT-A) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: TMT-B at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Stroop test at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Benton Judgment of Line Orientation (JLO) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Verbal fluency test at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Boston Naming Test (BNT) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Controlled Oral Word Association Test (COWAT) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Mini-Mental State Examination (MMSE) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Montreal Cognitive Assessment (MoCA) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Activity of daily living (ADL) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
Secondary outcomes:
measure: Global function at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Neuropsychiatric Inventory (NPI) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
Other outcomes:
measure: Hamilton Depression Scale (HAMD) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Geriatric Depression Scale (GDS) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Regulation of endothelial progenitor cell at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Transcranial Doppler (TCD) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Carotid duplex ultrasonic (CDU) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: Arterial spin labeling (ASL) MRI at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
measure: White matter hyperintensities (WMH) at endpoint and change from baseline
timeFrame: 48 weeks post-dose and change from baseline
Locations:
city: Tianjin
country: China
facility: Tianjin Medicial University General Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University General Hospital
name: Nan Zhang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: