Phase I Trial of Autologous Induced Pluripotent Stem Cell-derived Dopaminergic Progenitor Cell Transplantation for Parkinson's Disease
Overview
- Phase
- Phase 1
- Intervention
- autologous dopaminergic cell implantation
- Conditions
- Parkinson Disease
- Sponsor
- Jeffrey S. Schweitzer, MD, PhD
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Safety and Tolerability
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
The goal of this clinical trial is to assess the safety and tolerability of the surgical transplantation of dopaminergic progenitor cells into the brains of participants with Parkinson's disease. The transplanted dopaminergic cells will be derived from the participant's own skin cells.
Detailed Description
This Phase I, open-label clinical trial aims to assess the feasibility and safety of autologous midbrain dopaminergic progenitor cell (mDAP) transplantation for the treatment of Parkinson's disease. mDAPs will be produced for each participant from a fibroblast sample and then transplanted bilaterally into the putamen under general anesthesia. The study will assess the safety and tolerability of the cell transplant procedure through clinical assessments and neuroimaging (CT, MRI and 18F-DOPA PET) over a 2-year follow-up period.
Investigators
Jeffrey S. Schweitzer, MD, PhD
George A. Lopez, MD Endowed Chair in Neurosurgery
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of Parkinson's Disease consistent with the Movement Disorders Society 2015 Parkinson's diagnostic criteria.
- •Age 45 - 80 years
- •English proficiency sufficient to understand the consent form and participate in a discussion of risks and benefits
- •At least 5 years since Parkinson's disease motor symptom onset
- •Modified Hoehn and Yahr stage 3-4 in "off"-medication state
- •Motor symptoms responsive to levodopa and/or dopamine agonist, defined as taking at least 300 mg/day of levodopa and exhibiting improvement between "off" and "on" MDS-UPDRS of at least 30%
- •At least 3 hours of cumulative "off" time per day
- •Stable regimen of Parkinson's medications, including levodopa and dopamine agonists, for at least 4 weeks prior to screening.
- •Acceptable surgical laboratory values including:
- •Platelets \> 100×109/L (transfusion independent)
Exclusion Criteria
- •Subjects unable to give consent due to dementia or psychosis.
- •Montreal Cognitive Assessment (MoCA) score \< 26
- •Subjects with a first-degree relative with Parkinson's disease or with a known genetic mutation predisposing to the development of Parkinson's disease (i.e. this initial study is confined to the more common "sporadic" vs a "genetic" form of the disease).
- •Atypical Parkinsonism (Parkinson's-Plus syndrome, secondary parkinsonism)
- •Moderate or severe levodopa-induced dyskinesias in any body segment (such patients were found to be more prone to graft-induced dyskinesias in the fetal tissue studies that are proof of priniciple for this therapy)
- •Neurologic history or imaging demonstrating brain pathology not directly related to Parkinson's disease that is likely to interfere with study compliance or assessment of Parkinson's related motor disability.
- •History of stroke or transient ischemic attack
- •History of subarachnoid hemorrhage
- •Presence or history of psychosis within 12 months of screening
- •Suicidal ideation associated with intent or plan in the past 12 months (an answer of "yes" to C-SSRS questions 4 or 5) or with a previous history of suicide attempts in the past 5 years.
Arms & Interventions
Low dose administration
4 million autologous dopaminergic cells will be implanted into the putamen on each side of the brain
Intervention: autologous dopaminergic cell implantation
High dose administration
8 million autologous dopaminergic cells will be implanted into the putamen on each side of the brain
Intervention: autologous dopaminergic cell implantation
Outcomes
Primary Outcomes
Safety and Tolerability
Time Frame: 2 years from time of implantation
Incidence and severity of adverse events and serious adverse events
Secondary Outcomes
- 18-F DOPA PET uptake(2 years from time of implantation)
- Change in motor function(2 years from time of implantation)
- Change in "off" hours(2 years from time of implantation)
- Change in dyskinesia(2 years from time of implantation)
- Change in PD medication usage(2 years from time of implantation)
- Change in Parkinson's disease related quality of life(2 years from time of implantation)
- Global impression of change(2 years from time of implantation)