This combined phase 1/2a clinical trial is to investigate the safety, dose limiting toxicity (DLT), and exploratory efficacy of three repeated intraventricular administrations of NEUROSTEM® (human umbilical cord blood-derived mesenchymal stem cells) versus placebo via an Ommaya reservoir at 4 week intervals in patients with Alzheimer's disease.
The study is divided into the 2 stages: dose-escalation in stage 1 and randomized and multiple-dose cohort parallel design in stage 2.The target population for enrollment in this study is patients with mild to moderate Alzheimer's disease.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
46
Low dose: 1 x 10\^7cells/2mL 3 repeated intraventricular administrations via an Ommaya Reservoir at 4 week intervals High dose: 3 x 10\^7cells/2mL 3 repeated intraventricular administrations via an Ommaya Reservoir at 4 week intervals
Intraventricular administrations of 2mL Normal Saline at 4 week intervals via an Ommaya Reservoir, for a total of 3 administrations
Samsung Medical Center
Seoul, South Korea
Number of subjects with adverse events
Number of subjects with adverse event, number of subjects with normal range of vital signs, mixed lymphocyte reaction result, and laboratory examination result
Time frame: 24 weeks after the first dose
Change from the baseline in ADAS-Cog
Alzheimer's Disease assessment Scale-Cognitive Subscale
Time frame: 24 weeks after the first dose
Change from the baseline in S-IADL
Seoul Instrumental Activities of Daily Living
Time frame: 24 weeks after the first dose
Change from the baseline in K-MMSE
Mini Mental State Exmination Korean version
Time frame: 24 weeks after the first dose
Change from the baseline in CGA-NPI
Caregiver-administered Neuropsychiatric Inventory
Time frame: 24 weeks from the first dose
ADAS-Cog Response Rate
ADAS-cog response is defined as no worsening (no change or improvement on ADAS-cog score) of the ADAS-cog score at 24 weeks after the first administration compared to the baseline
Time frame: 24 weeks after the first dose
Change in CDR-SOB
Clinical Dementia Rating-Sum of Box
Time frame: 24 weeks after the first dose
Change in Florbetaben-PET
Florbetaben - Pittsburgh Compound B-positron emission tomography
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Time frame: 24 weeks after the first dose
Change in FDG-PET (CMRglc: regional cerebral metabolic rate for glucose)
fluorodeoxyglucose positron emission tomography
Time frame: 24 weeks after the first dose
Change in CIBIC-plus
The Clinician's Interview Based Impression of Change-plus
Time frame: 24 weeks after the first dose
Change from baseline in MRI (DTI mapping)
MRI Analysis
Time frame: 24 weeks after the first dose
Change from the baseline in CSF biomarkers
biomakrer analysis
Time frame: 24 weeks after the first dose