Safety and Efficiency of Umbilical Cord-derived Mesenchymal Stem Cells(UC-MSC) in Patients With Alzheimer's Disease

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the safety and the tolerability of UC-MSC (Human Umbilical Cord-Derived Mesenchymal Stem Cell) .This study is also to investigate the efficacy of this treatment in patients with Alzheimer's disease (AD).

Detailed Description
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To date, most AD patients who seek treatment already have neuritic plaques, neurofibrillary tangles, and neurodegeneration. At this stage of the disease, perhaps a multi-faceted approach to halt the toxicity of amyloid-β peptides and promote cell survival and/or replace lost cells would be most beneficial.Most of the treatments for Alzheimer disease are chemical drug which can improve the symptoms but is not able to inhibit the disease progression. Mesenchymal stem cells (MSCs) are multipotent cells that are being clinically explored as a new therapeutic for treating a variety of immune-mediated diseases.Preclinical studies of the mechanism of action suggest that the therapeutic effects afforded by MSC transplantation are short-lived and related to dynamic, paracrine interactions between MSCs and host cells.Clinical trials of MSCs thus far have shown no adverse reactions to allogeneic versus autologous MSC transplants. Clinical studies showed that umbilical cord derived MSC is immunologically stable and not toxic. This study is to evaluate the safety and the tolerability of UC-MSC (Human Umbilical Cord-Derived Mesenchymal Stem Cell).This study is also to investigate the efficacy of this treatment in patients with Alzheimer's disease.

Official Title
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Open-Label, Single-Center, Self Control, Phase Ⅰ/Ⅱ Clinical Trial to Evaluate the Safety and the Efficacy of UC-MSC in Patients With Alzheimer's Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Biological: Human Umbilical Cord Derived MSC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women who are age in the range of 50 to 85 All women: go into menopause Probable Alzheimer's disease as determined by NINCDS-ADRDA criteria MMSE score between 3 and 20, both inclusive Voluntarily participating subject who sign the consent form Exclusion Criteria: Subject with cancer Subject with positive test for Human Immunodeficiency Virus(HIV) Subject who cannot undergo Magnetic Resonance Imaging(MRI), computed tomography(CT) screening Subject with psychological diseases (i.e. depression, schizophrenia, bipolar disorder, etc) Subject with dementia caused by other than Alzheimer's disease (i.e. infection of central nervous system, Creutzfeld-Jacob disease, severe head trauma, Pick's disease, Huntington's disease, and Parkinson's disease) Subject with vascular dementia as determined by the clinical criteria of Design Standards Manual(DSM) IV and the imaging criteria of Erkinjuntii Subject with severe white matter hyperintensities (WMH); Severe WMH is defined that length of the deep white matter is 25 mm or longer and length of the periventricular capping/banding is 10 mm or longer. Subject who have had stroke in 3 months. Subject with severe kidney failure (1.5 mg/dL of serum creatinine or more) Hemoglobin < 9.5 g/dL for men, < 9.0 g/dL for women; Total WBC count < 3000/mm3; Total bilirubin ≥ 3 mg/dL Subject who is suspect to have active lung diseases based on check X-ray result Subject who have been excluded in the subject selection process for this study before A platelet count < 150,000/mm3; Plasma prothrombin time(PT)≥ 1.5; the international normalized ratio (INR) or activated partial thromboplastin time(aPTT)≥ 1.5X control value Subject who is determined inappropriate by the investigators

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human Umbilical Cord Derived MSC<br> | Biological: Human Umbilical Cord Derived MSC<br>* 20 million cells per subject（0.5×10^6 UC-MSCs per kg ） intravenous injection Infusion number:8 (Once every two weeks in the first month of each quarter) Time interval: two and a half months<br>* Other names: Other Name: UC-MSC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse event | All subjects: Follow-up a year Number of participants with adverse event, number of participants with normal range of vital signs and laboratory examination Indexes of safety evaluation: symptom or sign, laboratory examination, adverse reaction rate | 10 weeks from post-administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from the baseline in Alzheimer' s Disease Assessment Scale-cognitive subscale(ADAS-Cog) at 10 weeks post-dose | Changes from the baseline in ADAS-cog, Clinician's Interview-Based Impression of Change(CIBIC), mini-mental state examination（MMSE), CIBIC-plus, Activity of Daily Living Scales(ADL), Neuropsychiatric Inventory(NPI), serum transthyretin, amyloid beta and tau in cerebrospinal fluid, Thl/Th2 cytokines in the peripheral blood. | 10 weeks from post-administration |