Clinical trial NCT02886494: A Study to Evaluate Efficacy and Safety of BAC in Patient With Alzheimer's Disease or Vascular Dementia
Official title: A Randomized, Double-Blind, Vehicle-Controlled, Parallel, Phase II Study to Evaluate Efficacy and Safety of BAC in Patient With Alzheimer's Disease or Vascular Dementia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease or Vascular Dementia
Lead sponsor: Charsire Biotechnology Corp.
Sponsor class: INDUSTRY
First posted: 2016-09-01
Enrollment: 80
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Randomized, Double-Blind, Vehicle-Controlled, Parallel, Phase II Study to Evaluate Efficacy and Safety of BAC in Patient with Alzheimer's Disease or Vascular Dementia

Detailed description: This study was designed as a randomized, double-blind, vehicle-controlled and parallel trial to evaluate the efficacy and safety of BAC in patients with Alzheimer's disease or vascular dementia. The investigation product, BAC, is a potential anti-inflammatory agent consisted of Multi-Glycan Complex (MGC) from the Soybean extract. It aims to reduce the neruoinflammation in the Alzhemimer's disease and vascular dementia.

In each study site, eligible patients were randomized and stratified to 1 of 2 dementia types (Alzheimer's disease and non-Alzheimer's disease) in 3:1 ratio to receive either one of topical application of BAC or BAC matched vehicle, topical application on external nasal skin, scalp, and neck, 2 times daily, 30 g/day.

The treatment duration for each patient was 12 weeks, which consisted of 6 visits located at Screening (within 2 weeks before Baseline visit), Baseline (Week 0), Weeks 2, 4, 8, and Week 12 (Final). During the treatment period, patients may continue to receive medications or treatments routinely used for Alzheimer's disease or vascular dementia except those prohibited under this protocol.

Eligibility criteria: Inclusion Criteria:

1. With either gender aged at least 40 years old
2. With a diagnosis of one of the following disease i. Vascular dementia according to the NINDS-AIREN International Workshop criteria or ii. Alzheimer's disease according to the NIAAA criteria iii. "Mixed" dementia (possible Alzheimer's disease with cerebrovascular disease) according to the NIAAA criteria

   Note:
   1. NINDS-AIREN: National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et l'Enseignement en Neurosciences
   2. NIAAA: National Institute on Aging-Alzheimer's Association
3. With mild-to-moderate dementia (score of the Mini-Mental State Examination (MMSE) defined as between 10 to 24 and score of ADAS-Cog as at least 12)
4. Able to read, write, communicate, and understand cognitive testing instructions
5. Having a responsible caregiver who spends at least 4 hours daily with the patient. The caregiver will accompany the patient to all study visits, , supervise administration of study drug, and be able to assess the patient's condition
6. Patients and the responsible caregiver willing and able to provide written informed consent form

Exclusion Criteria:

1. With large vessel thrombosis (thrombotic stroke occurring in large arteries)
2. With radiological evidence of other brain disorders (subdural hematoma, post-traumatic / post-surgery)
3. With dementia caused by other brain diseases except Alzheimer's disease and vascular dementia (e.g. Parkinson's disease, demyelinated disease of the central nervous system, tumor, hydrocephalus, head injury, central nervous system infection including syphilis, acquired immune deficiency syndrome, etc.)
4. With clinical evidence of pulmonary, hepatic, gastrointestinal, metabolic, endocrine or other life threatening diseases judged by investigators not suitable to enter the study
5. With clinically unstable hypertension, diabetes mellitus, and cardiac disease for the last 3 months
6. Ever hospitalized for stroke or with acute coronary syndrome in the previous 3 months prior to screening
7. Drug or alcohol abuse within the previous 12 months of screening.
8. With one of the following abnormal laboratory parameters: hemoglobin \< 10 mg/dL or platelet \< 100\*109/L; creatinine or total bilirubin more than 1.5 times the upper limit value; alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphates (ALP), γ-glutamyl transferase (γ-GT) more than 2 times the upper limit of normal, or thyroid-stimulating hormone (TSH) more than 2.5 times the upper limit value or less than the lower limit value of normal
9. With severe depression graded by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and Cornell Scale for Depression in Dementia (CSDD)
10. With any uncontrolled illness (including, but not limited to, any of the following: ongoing or active infection including hepatitis B, C, and HIV, active bleeding, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris or, cardiac arrhythmia) judged by the investigator that entering the trial may be detrimental to the patient
11. With known or suspected hypersensitivity to any ingredients of study product and vehicle
12. Pregnant or lactating or premenopausal with childbearing potential but not taking reliable contraceptive method(s) during the study period

    Note: Reliable contraceptive methods will consider as below:
    1. Established use of oral, injected or implanted hormonal methods of contraception \> 3 months prior to baseline.
    2. Placement of an intrauterine device (IUD) or intrauterine system (IUS) \> 3 months prior to baseline.
    3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
    4. Partner male sterilization (i.e., vasectomy) \> 1 month of screening
13. Enrollment in any investigational drug trial within 4 weeks of screening visit
14. Experienced dosage increment of routinely use in drugs listed as follows within past three months before Screening visit

    1. medications/treatments for Alzheimer's disease or vascular dementia
    2. antipsychotic medications including but not limited to selective serotonin reuptake inhibitors (SSRIs), benzodiazepine (BZD)
    3. Vitamin B12
    4. drugs for thyroid disease
15. Current antiplatelet drug (antiaggregant) except dosage including but not limited to aspirin \<= 100mg/day, clopidogrel \<= 75mg/day, ticagrelor \<= 180mg/day, dipyridamole \<= 400mg/day
16. Caregivers who have psychotic symptoms, are imminently suicidal, have an unstable medical condition (e.g. recent heart attack, recent stroke, episodes of dizziness, fainting attacks) or significant orthopaedic problems.

Primary outcomes:
measure: Change in Alzheimer Disease Assessment Scale-cognitive (ADAS-cog) Score at Week 12 Visit Compared to Baseline
timeFrame: Week 12
Secondary outcomes:
measure: Change in ADAS-cog Score at All Post Treatment Visits (Except Week 12 Visit) Compared to Baseline
timeFrame: Week 4, 8
measure: Clinician's Interview Based Impression of Change-Plus Caregiver Input (CIBIC-plus) Score at All Post Treatment Visits
timeFrame: Week 4, 8, 12
measure: Change in Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Score at All Post Treatment Visits Compared to Baseline
timeFrame: Week 4, 8, 12
measure: Change in Mini-Mental State Examination (MMSE) Score at All Post Treatment Visits Compared to Baseline
timeFrame: Week 4, 8, 12
measure: Change in Neuropsychiatric Inventory (NPI) Score at All Post Treatment Visits Compared to Baseline: NPI-10 Frequency × Severity
timeFrame: Week 4, 8, 12
measure: Change in Neuropsychiatric Inventory (NPI) Score at All Post Treatment Visits Compared to Baseline: NPI-10 Caregiver Distress Score
timeFrame: Week 4, 8, 12
measure: Change in Neuropsychiatric Inventory (NPI) Score at All Post Treatment Visits Compared to Baseline: NPI-12 Frequency × Severity Score
timeFrame: Week 4, 8, 12
measure: Change in Neuropsychiatric Inventory (NPI) Score at All Post Treatment Visits Compared to Baseline: NPI-12 Caregiver Distress Score
timeFrame: Week 4, 8, 12
measure: Number of Participants With Adverse Events
timeFrame: AEs were reported through the study completion (up to 12 weeks)
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Clinical Research Consortium
state: Arizona
city: Little Rock
country: United States
facility: Woodland International Research Group
state: Arkansas
city: Rogers
country: United States
facility: Woodland Research Northwest, LLC
state: Arkansas
city: San Diego
country: United States
facility: Pacific Research Network, LLC
state: California
city: Atlanta
country: United States
facility: NeuroTrials Research, Inc.
state: Georgia
city: Springfield
country: United States
facility: The Cognitive and Research Center of NJ
state: New Jersey
city: Toms River
country: United States
facility: Advanced Memory Research Institute of NJ, PC
state: New Jersey
city: Brooklyn
country: United States
facility: SPRI
state: New York
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Dayton
country: United States
facility: Neurology Diagnostics, Inc.
state: Ohio
Study officials:
affiliation: Pacific Research Network
name: Stephen Thein
role: PRINCIPAL_INVESTIGATOR
References: