The Efficacy of DL-NBP in Patients With Mild Subcortical Ischemic Vascular Dementia

NCT03906123 | Unknown DMC

• 1 other identifier: TianjinMUGH001
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Subcortical Vascular Dementia; Cerebral Small Vessel Diseases

Keywords

DL-3-n-butylphthalide; vascular dementia; cerebral small vessel disease; cognitive function; cerebral blood flow

Outcome Measures

Primary Outcomes (14)

• 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

  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

Secondary Outcomes (2)

• Global function at endpoint and change from baseline

  48 weeks post-dose and change from baseline

• Neuropsychiatric Inventory (NPI) at endpoint and change from baseline

  48 weeks post-dose and change from baseline

Other Outcomes (7)

• Hamilton Depression Scale (HAMD) at endpoint and change from baseline

  48 weeks post-dose and change from baseline

• Geriatric Depression Scale (GDS) at endpoint and change from baseline

  48 weeks post-dose and change from baseline

• Regulation of endothelial progenitor cell at endpoint and change from baseline

  48 weeks post-dose and change from baseline

Study Arms (2)

NBP

EXPERIMENTAL

DL-3-n-butylphthalide (NBP), soft capsule, 200mg Tid, po, for 48 weeks.

Drug: NBP

Placebos

PLACEBO COMPARATOR

Placebo, soft capsule, 200mg Tid, po, for 48 weeks.

Drug: Placebos

Interventions

NBP DRUG

NBP soft capsules

Also known as: DL-3-n-butylphthalide

NBP

Placebos DRUG

Soft capsules manufactured to mimic NBP

Placebos

Eligibility Criteria

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

You may qualify if:

• Patients meet the criteria of major neurocognitive disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5);
• 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;
• 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;
• Patients or legal representative should sign the informed consent and have a reliable caregiver.

You may not qualify if:

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

Sponsors & Collaborators

• Tianjin Medical University General Hospital: lead

Study Sites (1)

Tianjin Medicial University General Hospital

Tianjin, Tianjin Municipality, 300052, China

RECRUITING

MeSH Terms

Conditions

Dementia, Vascular; Cerebral Small Vessel Diseases

Interventions

3-n-butylphthalide

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Arteriosclerosis; Intracranial Arterial Diseases; Dementia; Leukoencephalopathies; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Nan Zhang, MD, PhD

  Tianjin Medical University General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nan Zhang, MD, PhD

CONTACT

+8622 60119688; nkzhangnan@163.com

Mengya Xing, MD, PhD

CONTACT

+86 13702198695; xing_mengya@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: double-blind, randomized, placebo controlled study

Study Record Dates

• First Submitted: March 27, 2019
• First Posted: April 8, 2019
• Study Start: November 18, 2017
• Primary Completion: December 31, 2019
• Study Completion: January 31, 2020
• Last Updated: April 8, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available within 6 months of study completion.
• Access Criteria: Data access requests will be reviewed by an external Independent Review Panel. Requestors will be required to sign a Data Access Agreement.

Locations

CN (1)