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

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

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,

Study Overview

• Status: Unknown
• Conditions: Parkinson Disease
• Intervention / Treatment: Biological: human neural stem cell

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
• Enrollment (Anticipated): 12
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215004
      • Department of Neurology, Second Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 33 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Biological: human neural stem cell; human neural stem cell: 100ul/vessel，2 vessel/one bag，≥2×10 6cells/vessel

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PD therapy drugs	Reduction rate of PD therapy drugs	baseline and 16, 28 weeks

Collaborators and Investigators

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

Publications and helpful links

General 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, Bjorklund 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2017
• Primary Completion (Anticipated): June 1, 2018
• Study Completion (Anticipated): November 1, 2018

Study Registration Dates

• First Submitted: February 9, 2017
• First Submitted That Met QC Criteria: April 20, 2017
• First Posted (Actual): April 25, 2017

Study Record Updates

• Last Update Posted (Actual): September 14, 2017
• Last Update Submitted That Met QC Criteria: September 13, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Parkinson Disease; Neural stem cell; Nasal delivery
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: Second Affiliated Hospital

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Will decisde if the IPD based on patient consent

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No