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

• ClinicalTrials.gov Identifier: NCT03128450
• Recruitment Status: Unknown
• First Posted: April 25, 2017
• Last Update Posted: September 14, 2017
• Sponsor: Second Affiliated Hospital of Soochow University
• Information provided by (Responsible Party): Chun-Feng Liu, Second Affiliated Hospital of Soochow University

Tracking Information

• First Submitted Date: February 9, 2017
• First Posted Date: April 25, 2017
• Last Update Posted Date: September 14, 2017
• Actual Study Start Date: April 15, 2017
• Estimated Primary Completion Date: June 1, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 21, 2017)

The change of Unified Parkinson's Disease Reting Scale(UPDRS)score from baseline [ Time Frame: Baseline and 16, 28 weeks ]

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％

Original Primary Outcome Measures (submitted: April 20, 2017)

The change of Unified Parkinson's Disease Reting Scale(UPDRS)score from baseline [ Time Frame: Baseline and 3, 6 months ]

Improvement rate of UPDRS motor score defined as below: Reduction rate =（baseline score-3 or 6 months 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％

Current Secondary Outcome Measures (submitted: May 21, 2017)

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

Original Secondary Outcome Measures (submitted: April 20, 2017)

• motor function index [ Time Frame: baseline and 3, 6 months ]
  Hoehn-Yahr modified score
• Non-motor function score:cognitive function [ Time Frame: baseline and 3, 6 months ]
  Minimum Mental State Examination and Montreal Cognitive Assessment to assess cognitive function
• Non-motor function score:smell [ Time Frame: baseline and 3, 6 months ]
  Argentina Hyposmia Rating Scales is used to detect the smell
• Non-motor function score:fatigue [ Time Frame: baseline and 3, 6 months ]
  Fatigue Severity Scale to assess the extent of fatigue
• Non-motor function score:emotion [ Time Frame: baseline and 3, 6 months ]
  Hamilton Depression Scale to evaluate the degree of depression, Hamilton Anxiety Scale to evaluate the degree of anxiety
• Non-motor function score:non-motor symptoms [ Time Frame: baseline and 3, 6 months ]
  non-motor symptoms in PD patients is evaluated used Non-motor Symptoms Questionnaire
• Non-motor function score:autonomic symptoms [ Time Frame: baseline and 3, 6 months ]
  The scale for outcomes in PD for autonomic symptoms to assess autonomic dysfunction
• Non-motor function score:the quality of life. [ Time Frame: baseline and 3, 6 months ]
  The 39-item Parkinson's disease questionnaire to assess the quality of life.
• Immunological index [ Time Frame: baseline and 3, 6 months ]
  CD3(%)，CD4(%)，CD8(%)，Treg cells(%)
• Imaging index [ Time Frame: baseline and 3, 6 months ]
  Magnetic Resonance Imaging or positron emission tomography
• Blood routine examination [ Time Frame: baseline and 3, 6 months ]
  Blood routine examination includes the total number of red blood cells, hemoglobin, total number of white blood cells, white blood cells count, platelet count.
• Biochemical routine examination [ Time Frame: baseline and 3, 6 months ]
  Biochemical routine examination includes liver function, renal function, blood glucose, blood lipid
• Safety index [ Time Frame: 1,2,3,4,5,6 weeks and 3, 6 months ]
  Adverse Event and Serious Adverse Event

Current Other Pre-specified Outcome Measures (submitted: May 21, 2017)

PD therapy drugs [ Time Frame: baseline and 16, 28 weeks ]

Reduction rate of PD therapy drugs

Original Other Pre-specified Outcome Measures (submitted: April 20, 2017)

PD therapy drugs [ Time Frame: baseline and 3, 6 months ]

Reduction rate of PD therapy drugs

Descriptive Information

• Brief Title: A Study To Evaluate the Safety and Efficacy of Human Neural Stem Cells for Parkinson's Disease Patient
• Official Title: 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
• Brief Summary: 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

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.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Parkinson Disease

Intervention

Biological: human neural stem cell

human neural stem cell: 100ul/vessel，2 vessel/one bag，≥2×10 6cells/vessel

Study Arms

Experimental: h-NSC arm

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.

Intervention: Biological: human neural stem cell

Publications *

• Hallett PJ, Cooper O, Sadi D, Robertson H, Mendez I, Isacson O. Long-term health of dopaminergic neuron transplants in Parkinson's disease patients. Cell Rep. 2014 Jun 26;7(6):1755-61. doi: 10.1016/j.celrep.2014.05.027. Epub 2014 Jun 6.
• Kefalopoulou Z, Politis M, Piccini P, Mencacci N, Bhatia K, Jahanshahi M, Widner H, Rehncrona S, Brundin P, Björklund A, Lindvall O, Limousin P, Quinn N, Foltynie T. Long-term clinical outcome of fetal cell transplantation for Parkinson disease: two case reports. JAMA Neurol. 2014 Jan;71(1):83-7. doi: 10.1001/jamaneurol.2013.4749.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: April 20, 2017): 12
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 1, 2018
• Estimated Primary Completion Date: June 1, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 35 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03128450
• Other Study ID Numbers: Second Affiliated Hospital
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided
• Plan Description: Will decisde if the IPD based on patient consent

• Current Responsible Party: Chun-Feng Liu, Second Affiliated Hospital of Soochow University
• Original Responsible Party: Same as current
• Current Study Sponsor: Second Affiliated Hospital of Soochow University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jie Li; Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou

• PRS Account: Second Affiliated Hospital of Soochow University
• Verification Date: May 2017