<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04414813</url>
  </required_header>
  <id_info>
    <org_study_id>DFSC-2019（CR）-001</org_study_id>
    <nct_id>NCT04414813</nct_id>
  </id_info>
  <brief_title>Stereotactic Transplantation of hAESCs for Parkinson's Disease</brief_title>
  <official_title>Clinical Study of Stereotactic Transplantation of Human Amniotic Epithelial Stem Cells (hAESCs) in the Treatment of Parkinson's Disease (PD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai East Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai East Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the safety and efficacy of stereotactic&#xD;
      transplantation of hAESCs for Parkinson's disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study plans to recruit 3 participants with Parkinson's disease . Using stereotactic&#xD;
      technology, hAESCs will be accurately transplanted into the lateral ventricle. Therapeutic&#xD;
      effectiveness and safety of hAESCs on PD will be evaluated. hAESCs are derived from placental&#xD;
      amnion donated after cesarean section in healthy women. hAESCs is developed from the epiblast&#xD;
      as early as 8 days after fertilization, recent reports indicate that hAESCs have some&#xD;
      characteristics of neural stem cell. These cells are able to differentiate into dopaminergic&#xD;
      neurons and secrete dopamine and various neurotrophic factors. These HAESCs could be seen as&#xD;
      one of the best potential stem cell source for treating Parkinson's disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 8, 2020</start_date>
  <completion_date type="Actual">February 8, 2023</completion_date>
  <primary_completion_date type="Actual">February 8, 2023</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>The study plans to recruit 3 patients who meet the criteria. 50 millions HAESCs will be transplanted to participants with PD.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with adverse event and serious adverse event</measure>
    <time_frame>12 months</time_frame>
    <description>An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. A serious adverse event is defined as an adverse event that meets at least one of the following serious criteria: • fatal • life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • congenital anomaly/birth defect • other significant medical hazard. Whether an adverse event was treatment-related (TRAE) or not was determined by investigator.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Unified Parkinson's Disease Rating Scale (UPDRS) in ON and OFF state</measure>
    <time_frame>day 0, 1 month, 2 month, 3 month, 6 month, 9 month and 12 month.</time_frame>
    <description>UPDRS is used for evaluating the impairment and disability associated with Parkinson's Disease (PD). It consists of four sections: (1) Mentation, behavior, and mood; (2) Activities of daily living (ADLs); (3) Motor; and (4) Complications.&#xD;
The UPDRS score ranges from 0 to 199, with higher score indicating greater disability.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the Hoehn and Yahr scale</measure>
    <time_frame>day 0, 1 month, 2 month, 3 month, 6 month, 9 month and 12 month.</time_frame>
    <description>Hoehn and Yahr scale is used to provide a general estimate of clinical function of PD patients, combining functional deficits (disability) and objective signs (impairment). The Hoehn and Yahr score ranges from 0 to 5, with higher score indicating higher dysfunction of PD patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Parkinson's Disease Questionnaire (PDQ-39)</measure>
    <time_frame>day 0, 1 month, 2 month, 3 month, 6 month, 9 month and 12 month.</time_frame>
    <description>PDQ-39 provides the evidence of the quality of life of a PD patient. The higher the score, the lower the quality of life of PD patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the Schwab and England score</measure>
    <time_frame>day 0, 1 month, 2 month, 3 month, 6 month, 9 month and 12 month.</time_frame>
    <description>The Schwab and England scale develop a scale that describes the capacity of daily living shown by a PD patient. It measures the following three areas: dependence, abilities, and awareness. The Schwab and England scores range from 0% to 100%, with higher scores indicating greater healthy status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levodopa equivalent daily dose</measure>
    <time_frame>day 0, 1 month, 2 month, 3 month, 4 month, 5 month, 6 month, 9 month and 12 month.</time_frame>
    <description>Differences in daily dosage of levodopamine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cranial doparmin transporter measured by positron emission tomography(PET)-magnetic resonance Imaging(MRI)</measure>
    <time_frame>4 month, 6 month</time_frame>
    <description>Changes of cranial expression of dopamine transporter investigated by PET-MR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose metabolism measured by 18F-Fluoro-2-deoxy-glucose (FDG) PET scan</measure>
    <time_frame>4 month, 6 month</time_frame>
    <description>Changes in cranial glucose metabolism investigated by PET-MR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differences in biochemical indicators of cerebrospinal fluid</measure>
    <time_frame>day 0, 1 month, 2 month, 3 month, 4 month,5 month,6 month, 9 month and 12 month.</time_frame>
    <description>Cerebrospinal fluid indicator tests include biochemical indicators and the following parameters: Dopamine (DA), high vanillic acid (HVA), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (MHPG), α synuclein (α-synuclein), amyloid deposition (Aβ42), Tau protein (Tau) Protein, Neurofilament light (NF-L), and yKL-40 (YKL-40).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Parkinson's Disease</condition>
  <arm_group>
    <arm_group_label>hAESCs treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>50 millions hAESCs are transplanted to participants with PD.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Human Amniotic Epithelial Stem Cells</intervention_name>
    <description>Stereotactic transplantation of hAESCs for participants with PD.</description>
    <arm_group_label>hAESCs treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. 30-70 years old, with primary Parkinson's disease more than 5 years, male or female;&#xD;
&#xD;
          2. The &quot;off-stage&quot;Hohen and Yahr grade of Parkinson's disease is from 2 to 4; and&#xD;
             the&quot;off-stage&quot;UPDRS score is 38-70, difference between two scores before treatment is&#xD;
             less than 10% ;&#xD;
&#xD;
          3. The dosage of medicine is stable for more than 3 months;&#xD;
&#xD;
          4. Levodopa treatment was effective ;&#xD;
&#xD;
          5. Stable condition, good control of complications, no general anesthesia&#xD;
             contraindications, no contraindications to stereotactic surgery and other conditions&#xD;
             that interfere with clinical evaluation;&#xD;
&#xD;
          6. No abnormalities affecting cell transplantation were found through head MRI;&#xD;
&#xD;
          7. Patients shall be properly cared during treatment, and caregivers can provide&#xD;
             assistance to the researcher if necessary.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Atypical Parkinson's disease, such as Parkinson's syndrome, secondary Parkinson's&#xD;
             disease;&#xD;
&#xD;
          2. Only having tremor syndrome;&#xD;
&#xD;
          3. Serious movement disorders and cannot complete any routine exercise tasks;&#xD;
&#xD;
          4. Symptoms of severe neurological deficits caused by other diseases;&#xD;
&#xD;
          5. Severe mental symptoms or dementia;&#xD;
&#xD;
          6. Patients are unwilling to cooperate or incapable of completing self-evaluation, and&#xD;
             cannot complete the evaluator with the help of a doctor;&#xD;
&#xD;
          7. History of striatum or extrapyramidal surgery, including deep brain stimulation (DBS);&#xD;
&#xD;
          8. Ongoing treatment of apomorphine injecting ;&#xD;
&#xD;
          9. Coagulation disorders or ongoing anticoagulation therapy;&#xD;
&#xD;
         10. Women of childbearing age who do not take effective contraception;&#xD;
&#xD;
         11. Pregnant or lactation;&#xD;
&#xD;
         12. Patients who have participated in other clinical studies of drugs or medical devices&#xD;
             within 3 months;&#xD;
&#xD;
         13. Botox toxin, phenol, subarachnoid injection of baclofen or interventional therapy for&#xD;
             the treatment of dystonia or spasticity within 6 months;&#xD;
&#xD;
         14. History of seizures or taking prophylactic anti-epileptic drugs;&#xD;
&#xD;
         15. General anesthesia or stereotactic surgery contraindications, such as sleep apnea,&#xD;
             chronic obstructive pulmonary disease;&#xD;
&#xD;
         16. Other circumstances judged by the investigator that may cause negative effect to the&#xD;
             subject;&#xD;
&#xD;
         17. Alcohol or drug abuse;&#xD;
&#xD;
         18. Used diazepam within 3 months;&#xD;
&#xD;
         19. Severe cognitive impairment, depression, or behavioral disorder, defined as the&#xD;
             Mini-Mental State Assessment Scale (MMSE) of less than 26 points, and the Hamilton&#xD;
             Depression Rating Scale (HAMD) of greater than 35 points;&#xD;
&#xD;
         20. Chest CT shows active disease or tumor;&#xD;
&#xD;
         21. Currently suffering from or ever had a tumor other than cutaneous basal cell tumor and&#xD;
             cervical carcinoma in situ;&#xD;
&#xD;
         22. The detection of HIV, hepatitis B virus(HBV), hepatitis C virus (HCV), syphilis and&#xD;
             other infection indicators before surgery can not exclude HIV and syphilis infection;&#xD;
&#xD;
         23. Abnormal liver and kidney normal function tests in the laboratory, liver and kidney&#xD;
             function is defined as Alanine aminotransferase（ALT）, Aspartate aminotransferase（AST）&#xD;
             is less than 2.5 times the upper limit of normal, blood urea nitrogen (BUN) and&#xD;
             Creatinine（Cr） are less than the upper limit of normal.&#xD;
&#xD;
         24. Other situations not suitable for enrollment judged by investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>WU Jingwen, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai East Hospital, China</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>WU Jingwen</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>May 21, 2019</study_first_submitted>
  <study_first_submitted_qc>May 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>April 11, 2023</last_update_submitted>
  <last_update_submitted_qc>April 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Parkinson's Disease</keyword>
  <keyword>stereotactic transplantation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04414813
org study id: DFSC-2019（CR）-001
nct id: NCT04414813
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the safety and efficacy of stereotactic
      transplantation of hAESCs for Parkinson's disease.
The study plans to recruit 3 participants with Parkinson's disease . Using stereotactic
      technology, hAESCs will be accurately transplanted into the lateral ventricle. Therapeutic
      effectiveness and safety of hAESCs on PD will be evaluated. hAESCs are derived from placental
      amnion donated after cesarean section in healthy women. hAESCs is developed from the epiblast
      as early as 8 days after fertilization, recent reports indicate that hAESCs have some
      characteristics of neural stem cell. These cells are able to differentiate into dopaminergic
      neurons and secrete dopamine and various neurotrophic factors. These HAESCs could be seen as
      one of the best potential stem cell source for treating Parkinson's disease.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: The study plans to recruit 3 patients who meet the criteria. 50 millions HAESCs will be transplanted to participants with PD.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants with adverse event and serious adverse event
time frame: 12 months
description: An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. A serious adverse event is defined as an adverse event that meets at least one of the following serious criteria: • fatal • life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • congenital anomaly/birth defect • other significant medical hazard. Whether an adverse event was treatment-related (TRAE) or not was determined by investigator.
measure: Changes in Unified Parkinson's Disease Rating Scale (UPDRS) in ON and OFF state
time frame: day 0, 1 month, 2 month, 3 month, 6 month, 9 month and 12 month.
description: UPDRS is used for evaluating the impairment and disability associated with Parkinson's Disease (PD). It consists of four sections: (1) Mentation, behavior, and mood; (2) Activities of daily living (ADLs); (3) Motor; and (4) Complications.
The UPDRS score ranges from 0 to 199, with higher score indicating greater disability.
measure: Changes in the Hoehn and Yahr scale
time frame: day 0, 1 month, 2 month, 3 month, 6 month, 9 month and 12 month.
description: Hoehn and Yahr scale is used to provide a general estimate of clinical function of PD patients, combining functional deficits (disability) and objective signs (impairment). The Hoehn and Yahr score ranges from 0 to 5, with higher score indicating higher dysfunction of PD patients.
measure: Changes in Parkinson's Disease Questionnaire (PDQ-39)
time frame: day 0, 1 month, 2 month, 3 month, 6 month, 9 month and 12 month.
description: PDQ-39 provides the evidence of the quality of life of a PD patient. The higher the score, the lower the quality of life of PD patients.
measure: Changes in the Schwab and England score
time frame: day 0, 1 month, 2 month, 3 month, 6 month, 9 month and 12 month.
description: The Schwab and England scale develop a scale that describes the capacity of daily living shown by a PD patient. It measures the following three areas: dependence, abilities, and awareness. The Schwab and England scores range from 0% to 100%, with higher scores indicating greater healthy status.
measure: Levodopa equivalent daily dose
time frame: day 0, 1 month, 2 month, 3 month, 4 month, 5 month, 6 month, 9 month and 12 month.
description: Differences in daily dosage of levodopamine
measure: Cranial doparmin transporter measured by positron emission tomography(PET)-magnetic resonance Imaging(MRI)
time frame: 4 month, 6 month
description: Changes of cranial expression of dopamine transporter investigated by PET-MR
measure: Glucose metabolism measured by 18F-Fluoro-2-deoxy-glucose (FDG) PET scan
time frame: 4 month, 6 month
description: Changes in cranial glucose metabolism investigated by PET-MR
measure: Differences in biochemical indicators of cerebrospinal fluid
time frame: day 0, 1 month, 2 month, 3 month, 4 month,5 month,6 month, 9 month and 12 month.
description: Cerebrospinal fluid indicator tests include biochemical indicators and the following parameters: Dopamine (DA), high vanillic acid (HVA), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (MHPG), α synuclein (α-synuclein), amyloid deposition (Aβ42), Tau protein (Tau) Protein, Neurofilament light (NF-L), and yKL-40 (YKL-40).
arm group label: hAESCs treatment
arm group type: Experimental
description: 50 millions hAESCs are transplanted to participants with PD.
intervention type: Biological
intervention name: Human Amniotic Epithelial Stem Cells
description: Stereotactic transplantation of hAESCs for participants with PD.
arm group label: hAESCs treatment
criteria: 
gender: All
minimum age: 30 Years
maximum age: 70 Years
healthy volunteers: No
last name: WU Jingwen, Dr
role: Principal Investigator
affiliation: Shanghai East Hospital, China
facility: 
country: China
responsible party type: Sponsor
mesh term: Parkinson Disease
sharing ipd: No