A Study To Evaluate the Safety and Efficacy of Human Neural Stem Cells for Parkinson's Disease Patient

Study Overview
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Brief Summary
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This Pilot study will evaluate the safety and Efficacy of an investigational cell transplantation therapy, h-NSC, in patients with Parkinson's disease, through nasal drug delivery, a new delivery way. All patients will receive the therapy, which consists of human neural stem cells,

Detailed Description
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h-NSC is a cellular therapeutic consisting of human fetal neural stem cells (h-NSC). h-NSC injection will be delivered through nasal way for patients with Parkinson's disease (PD). The study will enroll 12 moderate to severe PD patients to be treated with the cell injection therapy at the same dose. The total therapy course will be four weeks，one dose for one week. The follow up will be two times within 24 weeks after finishing the treatment. The main objective of the study is to evaluate the efficacy and safety of the cell transplantation by this new delivery way.

Official Title
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A Single Arm, Open-Label，Pilot Study to Evaluate the Safety and Efficacy of Human Neural Stem Cells Injection (ANGE-S003) Through Nasal Way Delivery to Patients With Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Biological: human neural stem cell


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient diagnosed with idiopathic PD, at least with two key symptoms (Static tremor, bradykinesia, rigidity ) , without any other evidence of Secondary Parkinson's syndrome. Disease course ≥7 years，modified Hoehn-Yahr is 3-5 stage Patient age ≥35 years Patients receiving a stable dose of levodopa for at least 1 months with the expectation that the treatment will remain unchanged throughout the course of the study The doses of levodopa ≥300mg •Signed informed consent form (ICF) by patient self or his law-in relationship before enrollment. Exclusion Criteria: Hepatic dysfunction(transaminase ≥1.5 normal range), Renal dysfunction(Cr>2.0mg/dl or 177μmol/L)，Cardiac dysfunction or other severe systematic diseases etc. Suffering malignancy or during anti-cancer treatment period. Pregancy, lactation or possible pregancy and plan to pregancy patient Attended other intervention clinical trial within 3 months aftre getting ICF, or during other ongoing intervention clinical trial Investigator think inappropriate patient for this protocol

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 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: h-NSC arm<br>human neural stem cell: 100ul/vessel，2 vessel/one bag，≥2×10 6cells/vessel，produced by Shanghai Angecon Biotechology Cooperate. One enrolled PD patient was given 2 vessels h-NSC througth nasal cavity weekly for 4 weeks。Total cell number will be over ≥4×10 6cells for one time. | Biological: human neural stem cell<br>* human neural stem cell: 100ul/vessel，2 vessel/one bag，≥2×10 6cells/vessel<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of Unified Parkinson's Disease Reting Scale(UPDRS)score from baseline | Improvement rate of UPDRS motor score defined as below: Reduction rate =（baseline score 16, 28 weeks score after therapy）/ baseline score×100%. Based on reduction rate, the efficacy can be defined as complete remission, partial remission, effective and invalid The reduction rate will be 100%, >50%, >25-50%, ≤ 25% for complete remission, partial remission, effective and invalid. The improvement rate =[(complete+partial+effective patient number)/total patient number]×100％ | Baseline and 16, 28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| motor function index | Hoehn-Yahr modified score | baseline and 16, 28 weeks | 
| Non-motor function score:cognitive function | Minimum Mental State Examination and Montreal Cognitive Assessment to assess cognitive function | baseline and 16, 28 weeks | 
| Non-motor function score:smell | Argentina Hyposmia Rating Scales is used to detect the smell | baseline and 16, 28 weeks | 
| Non-motor function score:fatigue | Fatigue Severity Scale to assess the extent of fatigue | baseline and 16, 28 weeks | 
| Non-motor function score:emotion | Hamilton Depression Scale to evaluate the degree of depression, Hamilton Anxiety Scale to evaluate the degree of anxiety | baseline and 16, 28 weeks | 
| Non-motor function score:non-motor symptoms | non-motor symptoms in PD patients is evaluated used Non-motor Symptoms Questionnaire | baseline and 16, 28 weeks | 
| Non-motor function score:autonomic symptoms | The scale for outcomes in PD for autonomic symptoms to assess autonomic dysfunction | baseline and 16, 28 weeks | 
| Non-motor function score:the quality of life. | The 39-item Parkinson's disease questionnaire to assess the quality of life. | baseline and 16, 28 weeks | 
| Immunological index | CD3(%)，CD4(%)，CD8(%)，Treg cells(%) | baseline and 16, 28 weeks | 
| Imaging index | Magnetic Resonance Imaging or positron emission tomography | baseline and 16, 28 weeks | 
| Blood routine examination | Blood routine examination includes the total number of red blood cells, hemoglobin, total number of white blood cells, white blood cells count, platelet count. | baseline and 16, 28 weeks | 
| Biochemical routine examination | Biochemical routine examination includes liver function, renal function, blood glucose, blood lipid | baseline and 16, 28 weeks | 
| Safety index | Adverse Event and Serious Adverse Event | 1,2,3,4,weeks and 16, 28 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson Disease, Neural stem cell, Nasal delivery