Clinical Research on Stem Cell Therapy for Parkinson's Disease

Research Design and Implementation

(1) Inclusion, Exclusion and Withdrawal Criteria for Participants

1. Case Inclusion Criteria: 1.1 Male and female individuals aged between 40 and 70 years old, excluding adolescent patients with Parkinson's disease. 1.2 According to the 2015 MDS Parkinson's disease diagnostic criteria, confirmed by a PI or other movement disorder experts based on medical history, physical examination and neurological examination. 1.3 Modified Hoehn and Yahr staging under levodopa withdrawal period is less than or equal to 3 levels. 1.4 Have applied levodopa-like drugs, and have a good response to dopaminergic treatment, that is, compared with the withdrawal period, the UPDRS score (combined Parkinson's disease rating scale) of the subjects during the on period decreased by more than 33%. 1.5 If the subject is taking any central nervous system acting drugs (such as benzodiazepines, antidepressants, hypnotics), the treatment plan must be optimized and stabilized 90 days before the screening visit. 1.6 At least 90 days before the screening, stable Parkinson's disease symptom treatment has been carried out, and no additional Parkinson's disease symptom treatment is needed from the baseline visit for at least one year. 1.7 Pregnant women use reliable contraceptive methods during the period from 30 days before the baseline visit to 6 months after taking the study drug. 1.8 Participants voluntarily join this study, sign the informed consent form, and fully understand the content, process and possible adverse reactions of the trial, and be able to complete the study according to the requirements of the trial protocol.
2. Case Exclusion Criteria: 2.1 Atypical or drug-induced Parkinson's disease. 2.2 Any limb UPDRS resting tremor score of 3 or higher. 2.3 Montreal Cognitive Assessment (MoCA) score lower than 25 points. 2.4 Clinical features of psychosis or refractory hallucinations. 2.5 Epilepsy history, and having seizures within the past 6 months. 2.6 Mental retardation, possible or definite suicidal thoughts or behaviors, etc. mental disorders or symptoms. 2.7 Chronic kidney disease: Glomerular filtration rate (GFR) < 50 ml/min/m2 as the diagnostic criterion. 2.8 Liver function changes: Alanine transaminase (ALT) > 150 U/L and/or total bilirubin > 1.6 mg/dl. 2.9 Clinical refractory orthostatic hypotension at the time of screening or at the baseline visit, with a systolic blood pressure change of greater than or equal to 20 mmHg and a diastolic blood pressure change of greater than or equal to 10 mmHg within 2 minutes from a sitting position to standing position, and ineffective with drug treatment or baseline sitting blood pressure less than 90/60 mmHg. 2.10 Congestive heart failure history, clinically significant bradycardia, second or third degree atrioventricular block. 2.11 Pulmonary disease: Chronic obstructive pulmonary disease (COPD) or moderate to severe asthma. 2.12 Active malignant tumors or diagnosed as malignant tumors within 5 years before the screening. 2.13 Any autoimmune disease or immunodeficiency diagnosis, including recent 3-year chemotherapy or current use of immunosuppressive treatment, white blood cell (WBC) < 3 × 103 cells/ml. 2.14 Moderate to severe cerebrovascular accident or traumatic brain injury history. 2.15 Within the past 3 months or planned within the next 6 months to undergo major surgery. 2.16 Clinically significant abnormalities in the laboratory study during the screening visit. 2.17 History of using study medication within 30 days before the screening visit. 2.18 History of brain surgery for Parkinson's disease. 2.19 Unable to return for clinical assessment, laboratory study or imaging assessment during the follow-up. 2.20 History of drug abuse. 2.21 Active anticoagulation treatment or abnormal INR. 2.22 Other situations that researchers consider would cause significant danger to the subject or complicate the study assessment after enrollment.
3. Withdrawal Criteria: 3.1 If the patient requests to withdraw or if the equivalent dose of levodopa changes by more than 30% compared to the baseline level, the subject is deemed unsuitable to continue the trial.
4. Number of enrolled cases: It is planned to include 20 subjects who meet the inclusion and exclusion criteria.
5. Administration route: Human umbilical cord mesenchymal stem cells were administered via intravenous infusion. Some subjects were also given the treatment through nasal instillation.
6. Administration method: Human umbilical cord mesenchymal stem cells were administered intravenously once every 2 weeks, for a total of 5 times. Among them, half of the subjects (10 people) received nasal instillation of human umbilical cord mesenchymal stem cells once in the morning and once in the evening each day from the 6th to the 8th day after each administration; the remaining subjects (10 people) received nasal instillation of the stem cell solvent (0.9% sodium chloride injection containing 5% human albumin, which is consistent in appearance, packaging, instructions for use, and labels with the nasal administration preparation of human umbilical cord mesenchymal stem cells) once in the morning and once in the evening each day from the 6th to the 8th day after each administration. All subjects should receive basic treatment simultaneously during the trial period.