Precise Transplantation of hAESCs Into the Ventricle for Parkinson's Disease.

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Primary Purpose

Status

Not yet recruiting

Phase

Early Phase 1

Locations

China

Study Type

Interventional

Intervention

hAESCs treatment

placebo (saline)

About this trial

This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson's Disease; stem cell

Eligibility Criteria

30 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

30-70 years old, with more than 5 years primary Parkinson's disease history, male or female;
The "off-age" UPDRS exercise score is between 38 and 70 points, two times before the operation, the "down period" UPDRS exercise score was stable, that is, (high value - low value) / high value ≤ 10%;
The Parkinson treatment is stable for more than 3 months;
Levodopa treatment was effective;
No general anesthesia contraindications, no contraindications to stereotactic surgery and other conditions that interfere with clinical evaluation;
No abnormalities affecting cell transplantation were found through the cranial MRI;
Patients shall be properly cared during treatment, and caregivers can provide transplantation situations and assistance to the researcher if necessary.

Exclusion Criteria:

Atypical Parkinson's disease, such as Parkinson's syndrome, secondary Parkinson's disease;
Only having tremor syndrome;
"off period" or "on period" has serious movement disorders and cannot complete any routine exercise tasks;
Symptoms of severe neurological deficits caused by other diseases;
Severe mental symptoms or dementia;
Patients are unwilling to cooperate or incapable of completing self-evaluation, and cannot complete the evaluator with the help of a doctor;
History of striatum or extrapyramidal surgery, including deep brain stimulation (DBS);
Injecting apomorphine treatment;
Abnormal blood coagulation or ongoing anticoagulation therapy;
Women of childbearing age who do not take effective contraception;
Pregnant or lactation;
Patients who have participated in other clinical studies of drugs or medical devices within 3 months;
Botox toxin, phenol, subarachnoid injection of baclofen or interventional therapy for the treatment of dystonia or spasticity within 6 months;
History of seizures or prophylactic anti-epileptic drugs;
Alcohol or drug abuse;
Severe cognitive impairment, depression, or behavioral disorder, defined as the Mini-Mental State Assessment Scale (MMSE) of less than 26 points, and the Hamilton Depression Rating Scale (HAMD) of greater than 35 points;
Malignant tumor or active infection within 5 years;
Serum virology showed positive results for hepatitis C virus (HCV) , treponema pallidum (TP) or HIV; Active hepatitis B (hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) positive, and peripheral blood HBV DNA titer ≥1×10^3 IU/ mL);
Abnormal liver and kidney function tests in the laboratory, liver and kidney function is defined as Alanine aminotransferase（ALT), Aspartate aminotransferase（AST) is less than 2.5 times the upper limit of normal, blood urea nitrogen (BUN) and Creatinine（Cr) are less than the upper limit of normal.
Other conditions considered ineligible for inclusion by the investigator.

Sites / Locations

Jingwen Wu

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

hAESCs treatment

Control group

Arm Description

A total of 6 times hAESCs transplants will be performed. 50 million (in 2ml) hAESCs will be transplanted into the ventricle of participants through the Ommaya sac (set as day 0 at the beginning of the trial). Subsequently, hAESCs ventricle transplants will be performed at 1 month ±5 days, 2 months ±5 days, 3 months ±5 days, 6 months ±5 days, and 9 months ±5 days after the first cell transplantation, with a volume of 50 million cells (in 2 ml) each time.

Four times hAESCs transplants and two times placebo (cell preservation solution) injections will be performed by Ommaya sac. 50 million (in 2ml) hAESCs will be transplanted into the ventricle of participants (set as day 0 at the beginning of the trial). Subsequently, hAESCs will be transplanted into the ventricle for 3 times, respectively, at 1 month ±5 days , 2 months±5 days , and 3 months ±5 days after the first cell transplantation, with a volume of 50 million cells (in 2 ml) each time. Ventricle injection of 2 ml placebo (cell preservation solution) will be performed at 6 months ±5 days and 9 months ±5 days after the first cell transplantation.

Outcomes

Primary Outcome Measures

Number of participants with adverse event (AE), serious adverse event(SAE) and adverse events of special interest(AESI)

AE occurring throughout the study period will be evaluated using the CTCAE V5.0 standard. AE/SAE and AESI were evaluated after Ommaya sac installation by laboratory examination, measurement of vital signs, physical examination, and subjects' symptoms to detect new abnormalities and/or deterioration of previous conditions and evaluate the safety of the study. AESI is defined as intracranial infection, hemorrhage, rejection, and edema within 7 days after Ommaya sac installation, as well as acute allergic reactions and ectopic mass formation associated with study therapy.

Secondary Outcome Measures

Changes in Unified Parkinson's Disease Rating Scale (UPDRS) in OFF state between the experimental group and the control group at 12 months after the first hAESCs treatment

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

Changes in the Hoehn and Yahr scale

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.

Changes in the Schwab and England score

The Schwab and England score develop a scale that describes the capacity of daily living shown by a PD patients. It measures the following three areas: dependence, abilities, and awareness. The Schwab and England score range from o% to 100%, with higher scores indicating greater healthy status.

Changes in the Parkinson's Disease Questionnaire (PDQ-39)

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.

Changes in the Hamilton Depression (HAMD) Scale

HAMD is the most widely used scale in clinical evaluation of depression in PD patients. This project takes 8 points as the critical value of depression, and the total score over 35 points is considered as severe depression, more than 20 points is likely to be diagnosed with depression, less than 8 points is not depressed.

Differences in biochemical indicators of cerebrospinal fluid

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).

Cranial dopamin transporter measured by positron emission tomography (PET)- magnetic resonance imaging (MRI)

Changes of cranial expression of dopamine transporter investigated by PET-MR

Glucose metabolism measured by 18F-Fluoro-2-deoxy-glucose (FDG) PET scan

Changes of cranial glucose metabolism investigated by PET-MR

Full Information

NCT ID

NCT05435755

First Posted

March 15, 2022

Last Updated

October 27, 2022

Sponsor

Shanghai East Hospital

Collaborators

Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China

1. Study Identification

Unique Protocol Identification Number

NCT05435755

Brief Title

Precise Transplantation of hAESCs Into the Ventricle for Parkinson's Disease.

Official Title

The Precise Transplantation of Human Amniotic Epithelial Stem Cells Into the Ventricle Through Surgical Robot in the Treatment of Parkinson's Disease.

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

December 2, 2022 (Anticipated)

Primary Completion Date

July 30, 2023 (Anticipated)

Study Completion Date

August 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shanghai East Hospital

Collaborators

Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to evaluate the safety of multiple treatments of hAESCs treatments, while exploring the effectiveness of hAESCs treatments for PD.

Detailed Description

The study plans to use randomized controlled trial and recruit 12 participants with Idiopathic Parkinson's disease. The trial will be divided into two groups, hAESCs treatment group and control group, each group 6 subjects. Through surgical robot technology, hAESCs will be precisely multiple transplanted into the lateral ventricles, that is two times consolidation hAESCs treatments or placebo were added to the four times basic hAESCs treatments. Therapeutic safety and effectiveness of multiple treatments of hAESCs on PD will be evaluated to further develop the optimal stem cell treatment strategy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson's Disease

Keywords

Parkinson's Disease; stem cell

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Model Description

The study plans to recruit 12 patients who meet the criteria. 50 millions hAESCs will be transplanted to participants with PD.

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

hAESCs treatment

Arm Type

Experimental

Arm Description

A total of 6 times hAESCs transplants will be performed. 50 million (in 2ml) hAESCs will be transplanted into the ventricle of participants through the Ommaya sac (set as day 0 at the beginning of the trial). Subsequently, hAESCs ventricle transplants will be performed at 1 month ±5 days, 2 months ±5 days, 3 months ±5 days, 6 months ±5 days, and 9 months ±5 days after the first cell transplantation, with a volume of 50 million cells (in 2 ml) each time.

Arm Title

Control group

Arm Type

Placebo Comparator

Arm Description

Four times hAESCs transplants and two times placebo (cell preservation solution) injections will be performed by Ommaya sac. 50 million (in 2ml) hAESCs will be transplanted into the ventricle of participants (set as day 0 at the beginning of the trial). Subsequently, hAESCs will be transplanted into the ventricle for 3 times, respectively, at 1 month ±5 days , 2 months±5 days , and 3 months ±5 days after the first cell transplantation, with a volume of 50 million cells (in 2 ml) each time. Ventricle injection of 2 ml placebo (cell preservation solution) will be performed at 6 months ±5 days and 9 months ±5 days after the first cell transplantation.

Intervention Type

Biological

Intervention Name(s)

hAESCs treatment

Intervention Description

Precise Transplantation of hAESCs Into the Ventricle for Parkinson's Disease.

Intervention Type

Biological

Intervention Name(s)

placebo (saline)

Intervention Description

2 times placebo (normal saline) injections as control group

Primary Outcome Measure Information:

Title

Number of participants with adverse event (AE), serious adverse event(SAE) and adverse events of special interest(AESI)

Description

AE occurring throughout the study period will be evaluated using the CTCAE V5.0 standard. AE/SAE and AESI were evaluated after Ommaya sac installation by laboratory examination, measurement of vital signs, physical examination, and subjects' symptoms to detect new abnormalities and/or deterioration of previous conditions and evaluate the safety of the study. AESI is defined as intracranial infection, hemorrhage, rejection, and edema within 7 days after Ommaya sac installation, as well as acute allergic reactions and ectopic mass formation associated with study therapy.

Time Frame

12 Months

Secondary Outcome Measure Information:

Title

Changes in Unified Parkinson's Disease Rating Scale (UPDRS) in OFF state between the experimental group and the control group at 12 months after the first hAESCs treatment

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

Time Frame