Alzheimer's Disease
Conditions
Keywords
human umbilical cord blood derived mesenchymal stem cells, stem cells, alzheimer's disease, cognitive ability, mesenchymal stem cells, cord blood
Brief summary
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.
Detailed description
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.
Interventions
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
OTHERNormal saline 2mL
Intraventricular administrations of 2mL Normal Saline at 4 week intervals via an Ommaya Reservoir, for a total of 3 administrations
Sponsors
Medipost Co Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Stage 1: 9 subjects (3 subjects for low dose and 6 subjects for high dose) Stage 2: 36 subjects ( 24 subjects for high dose and 12 subjects for placebo) A total of 45 subjects to be enrolled
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1 stage Inclusion Criteria: 1. Korean male or female at 50 -85 years of age 2. Diagnosis of Probable Alzheimer type according to NINCDS-ADRDA criteria at Visit 1 (Screening) 3. Korea Mini-Mental State Examination (KMMSE) score of 18 - 26 at Visit 1 (Screening) 4. Positive for Amyloid on PIB-PET or Florbetaben PET 5. A subject who is informed of the clinical trial and signs a consent form (if unable to sign, a consent from a legally acceptable representative is required) 2 stage Inclusion Criteria: 1. Korean male or female at 50 -85 years of age 2. Diagnosis of Probable Alzheimer type or mild cognitive impairment due to Alzheimer's disease (stage A) according to NIA-AA criteria at Visit 1(Screening) 3. Korea Mini-Mental State Examination (KMMSE) score of over 18 at Visit 1 (Screening) 4. Positive for Amyloid on Florbetaben PET 5. A subject with neurodegeneration (mild atrophy of the brain) as confirmed by MRI 6. A subject who is informed of the clinical trial and signs a consent form (if unable to sign, a consent from a legally acceptable representative is required)
Exclusion criteria
1. Concurrent mental disorder (such as schizophrenia, depression, bi-polar diseases or others) aside from dementia 2. Concurrent dementia as a result of other neurodegenerative disorders (due to infectious disease of the central nervous system such as HIV, syphilis), head injury, Creutzfeld-Jacob disease, Pick's disease, Huntington's disease, or Parkinson's disease 3. Diagnosis of severe white matter hyperintensitivity (WMH) according to CREDOS (Clinical REsearch Center for Dementia of South Korea), which is defined as ≥ 25mm of the deep white matter and ≥ 10mm of the periventricular capping/banding in lengths 4. History of stroke within 3 months prior to study enrollment 5. Severe liver disorder (equivalent to double the normal values of ALT and AST) at Visit 1 6. Severe kidney disorder (serum creatinine ≥1.5mg/dL) at Visit 1 7. Pregnant or lactating females 8. Abnormal Laboratory findings at Visit 1 * Hemoglobin \< 9.5 g/dL for male and \<9.0 g/dL for female * Total WBC Count \< 3000/mm3 * Total Bilirubin \>= 3 mg/dL 9. Suspected active lung disease based on chest X-ray at Visit 1 10. Woman of childbearing age who refuses to practice medically acceptable contraceptive method (post menopausal patient with no menstruation for at least 12 months is considered as infertile) 11. History of screening failure for the clinical trial of NEUROSTEM® in the past 6 months 12. Participation in another clinical trial in the past 3 months prior to the beginning (Week 0) of this clinical trial 13. Bleeding disorder (abnormal blood coagulation test result (i.e. platelet count of \< 150,000/mm3, PT ≥ 1.5 INR, or aPTT ≥ 1.5 x control anti-coagulant or anti-platelet, without anticoagulant or anti-platelet therapy) 14. Diagnosis of cancer (of any body system, including brain tumor) 15. Substance/alcohol abuse 16. Contraindicated for any of the tests performed during the clinical trial period (for example, MRI, CT, PET) 17. A subject in whom Ommaya reservoir insertion is considered difficult 18. Whom the principal investigator considers inappropriate for participation in the study due to any reasons other than those listed above
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with adverse events | 24 weeks after the first dose | Number of subjects with adverse event, number of subjects with normal range of vital signs, mixed lymphocyte reaction result, and laboratory examination result |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from the baseline in S-IADL | 24 weeks after the first dose | Seoul Instrumental Activities of Daily Living |
| Change from the baseline in K-MMSE | 24 weeks after the first dose | Mini Mental State Exmination Korean version |
| Change from the baseline in CGA-NPI | 24 weeks from the first dose | Caregiver-administered Neuropsychiatric Inventory |
| ADAS-Cog Response Rate | 24 weeks after the first dose | 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 |
| Change in CDR-SOB | 24 weeks after the first dose | Clinical Dementia Rating-Sum of Box |
| Change from the baseline in ADAS-Cog | 24 weeks after the first dose | Alzheimer's Disease assessment Scale-Cognitive Subscale |
| Change in FDG-PET (CMRglc: regional cerebral metabolic rate for glucose) | 24 weeks after the first dose | fluorodeoxyglucose positron emission tomography |
| Change in CIBIC-plus | 24 weeks after the first dose | The Clinician's Interview Based Impression of Change-plus |
| Change from baseline in MRI (DTI mapping) | 24 weeks after the first dose | MRI Analysis |
| Change from the baseline in CSF biomarkers | 24 weeks after the first dose | biomakrer analysis |
| Change in Florbetaben-PET | 24 weeks after the first dose | Florbetaben - Pittsburgh Compound B-positron emission tomography |
Countries
South Korea
Outcome results
None listed