Parkinson'
Conditions
Sponsors
Kyoto University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)The patient has a diagnosis of PD (clinically established or clinically probable) in accordance with the MDS Clinical Diagnostic Criteria for Parkinson's Disease (2015). 2)The patient plans to undergo transplantation of human iPSC-derived dopaminergic progenitors. 3)The patient has a poor response to existing drug treatments. 4)The patient is >= 50 years and < 70 years of age at the time of informed consent. 5)The patient has had PD for at least 5 years. 6)The patient has both ON and OFF (as demonstrated by the MDS-UPDRS Part III and a symptom diary). 7)The patient is in stage 3 or higher on the Hoehn and Yahr scale at OFF time. 8)The patient is in stage 3 or lower on the Hoehn and Yahr scale at ON time. 9)The patient has an L-dopa response of 30% or more without influence of antiparkinsonian drugs. 10)The patient has a decrease pattern characteristic to PD in the basal ganglia region on DAT scan. 11)The patient has the following organ functions as determined by laboratory tests within 7 days before registration: i)Neutrophil count >= 2,000/microL ii)Platelet count >= 5.0 X 10^4/microL iii)AST, ALT =< 3.0 X upper limit of normal at the study site iv)Total bilirubin =< 1.5 X upper limit of normal at the study site v)eGFR >= 60 mL/min/1.73 m2 vi)eGFR (mL/min/1.73 m2) = 194 X Cr^-1.094 X age^-0.287 (X 0.739 for females) 12)The patient provides written informed consent to participate in the study. A patient who cannot write due to the disease may be enrolled if he or she provides verbal consent and a witness signs the informed consent form.
Exclusion criteria
Exclusion criteria: 1)The patient has a symptomatic organic lesion as detected by head MRI. 2)The patient has abnormal immune function. 3)The patient is demented or deemed at high risk of dementia. 4)The patient has bleeding tendency or abnormal coagulation function. 5)The patient is HBs antigen-positive, or HBs antibody- or HBc antibody-positive with evidence of HBV-DNA. 6)The patient is anti-HIV antibody-positive. 7)The patient is anti-HTLV-1 antibody-positive. 8)The patient has active infection such as hepatitis C or syphilis (STS/TPHA). 9)The patient has contraindication to the study drug (tacrolimus), concomitant drugs (e.g., levodopa, carbidopa, MRI contrast), and/or their components. 10)The patient has hypersensitivity to the study drug (tacrolimus), concomitant drugs (e.g., levodopa, carbidopa, MRI contrast), and/or their components. 11)The patient has severe allergic to gentamicin, a bovine-derived ingredient l or a pig-derived ingredient. 12)The patient has undergone transplantation of human iPSC-derived dopaminergic progenitors. 13)The patient has any of the following diseases concurrently: .Malignant neoplasm .Epilepsy .Mental disease (e.g., depression, bipolar disorder, schizophrenia) .Other serious concurrent diseases (e.g., cerebrovascular disorder, heart disease, chronic respiratory disease, inadequately controlled hypertension, diabetes mellitus) 14)The patient has a history of any of the following: .Malignant neoplasm .Epilepsy .Cerebral hemorrhage .Mental disease (e.g., depression, bipolar disorder, schizophrenia) .Pallidotomy, thalamotomy, or deep brain stimulation 15)The patient is pregnant or lactating, or does not agree to avoid pregnancy throughout the study. 16)The patient, in the opinion of the investigator or subinvestigator, is not appropriate to conduct the study safely.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1) Incidence and severity of adverse events 2) Presence or absence of graft expansion in the brain at 24 months after transplantation | — |
Secondary
| Measure | Time frame |
|---|---|
| <Safety endpoints> 1) Uptake of [18F]FLT 2) Uptake of [18F]GE180 3) Dyskinesia score 4) Graft size (MRI) <Efficacy endpoints> 1) MDS-UPDRS Part III total score (at ON and OFF times) 2) MDS-UPDRS Part II total score 3) MDS-UPDRS Part I total score 4) Sum score of MDS-UPDRS Part I, Part II, and Part III (at ON and OFF times) 5) Average daily ON duration (with or without dyskinesia) and OFF duration 6) Bradykinesia subscale 7) Uptake of [18F]FDOPA 8) Uptake on DAT scan 9) Parkinson's Disease Questionnaire (PDQ-39) 10) Hoehn and Yahr severity 11) L-dopa equivalent dose 12) Euro-QOL 5 Dimensions-5 Levels (EQ-5D-5L) 13) Work Productivity and Activity Impairment Questionnaire (WPAI) 14) Nursing care category | — |
Countries
Japan
Contacts
Public ContactNobukatsu Sawamoto
Kyoto University Hospital Department of Neurology
Outcome results
None listed