Parkinson Disease
Conditions
Brief summary
This research study is evaluating an investigational cell product called autologous induced pluripotent stem cell (iPSC)-derived dopamine neurons. This research study is a single-center Phase 1/2a clinical trial, which will test the safety of injecting the investigational cell product into the brain of subjects with Parkinson's disease.
Detailed description
The goal of this research study is to test a new treatment for Parkinson's disease. Parkinson's disease is a progressive disease that causes people to lose specific brain cells called midbrain dopamine neurons. When these dopamine neurons are lost, it leads to a lack of dopamine in the brain. When there is not enough dopamine, people with Parkinson's disease experience problems with their movement. This trial will test whether new dopamine neurons made from blood cells from subjects with Parkinson's disease are safe when surgically injected into the area of the brain affected (called the putamen) of the same subjects (called autologous transplantation). The trial will assess the safety of the injected cells and will also measure the effects of the transplanted autologous dopamine neurons on Parkinson's disease symptoms. At this time, autologous iPSC-derived midbrain dopamine neurons are available only through participation in the ongoing Phase 1/2a clinical trial. Expanded access or compassionate use outside of the trial is not available.
Interventions
BIOLOGICALAutologous midbrain dopamine neurons
The autologous midbrain dopamine neurons are an experimental cryopreserved cell product derived from human autologous induced pluripotent stem cells. The autologous midbrain dopamine neurons are surgically administered into the putamen. Six participants received unilateral transplantation into one putamen. Six participants will receive bilateral transplantation into both putamina during a single surgical session.
Sponsors
Penelope J. Hallett, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Oryon Cell Therapies
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Males and females between ages 55 to eighty. * Diagnosis of Parkinson's disease with motor symptoms by neurologist according to Movement Disorder Society (MDS) 2015 Clinical Diagnostic Criteria for Parkinson's disease. * Diagnosis of Parkinson's disease for at least 5 years. * Dopamine drug responsiveness demonstrated by a positive "on/off" test with at least a 30% improvement on UPDRS III (motor) scale. * No gross abnormalities on MRI, including hydrocephalus or extensive white matter disease. * No significant cognitive impairment (Montreal Cognitive Assessment). * No significant untreated depression (Beck Depression Inventory 2). * Up to date cancer screening per primary MD. * Able to understand trial requirements and intervention procedures and provide written informed consent.
Exclusion criteria
* History of intracranial surgeries. * Any previous thalamotomy, pallidotomy or deep brain stimulation. * Atypical Parkinsonism (Parkinsonism-Plus syndrome, secondary parkinsonism, hereditary parkinsonism) * History of psychiatric disorders including schizophrenia or psychosis likely to compromise with ability to comply with trial protocol requirements. * Prior history of intracerebral, subdural, or epidural hemorrhage. * History of malignancy within 5 years. * Inability to have an MRI. * Life expectancy \< 6 months due to concomitant illnesses. * Ingestion of investigational drug or recipient of investigational procedure within 6 months prior to trial. * Subjects with active cardiovascular and cerebrovascular disease within 6 months prior to signing the informed consent form: 1. History of severe heart failure (congestive heart failure of New York Heart Association Class II or above or left ventricular ejection fraction \< 35% by any examination method), unstable angina pectoris and myocardial infarction 2. Severe arrhythmia 3. History of cardiovascular surgery (cardiac, vascular stent surgery, angioplasty); 4. History of stroke or transient ischemic attack 5. History of subarachnoid hemorrhage 6. Subjects with major vascular diseases (aortic aneurysm, aortic dissecting aneurysm, internal carotid artery stenosis) * Hypertensive subjects with poorly controlled blood pressure (defined as blood pressure above 160/100 mmHg despite treatment with antihypertensive drugs) and subjects with severe postural hypotension. * Abnormal pre-operative coagulation labs. * Any necessary chronic anticoagulation medication in use (not including antiplatelet therapy and chronic NSAID). * Diabetic subjects with poorly controlled blood glucose (glycosylated hemoglobin \> 9.0%, or fasting plasma glucose (FPG) ≥ 11.1 mmol/L). * Active infectious disease. Subjects known to have tested positive for HIV, Human T-lymphotropic Virus, Hepatitis B Virus, Hepatitis C Virus, Cytomegalovirus (IgM \> IgG) and/or syphilis will be evaluated by an expert as to subject eligibility based on the subject's infectious status. * Any illness which, in the Investigator's judgment, will interfere with the subject's ability to comply with the protocol, compromise subject safety, or interfere with the interpretation of the trial results. * Active clinical infection being treated by antibiotics within one week of enrollment. * Known drug or alcohol dependence or any other clinical factors or conditions (for example, history of seizures) which will interfere with the trial conduct or interpretation of the results or who in the opinion of the investigator are not suitable to participate. * Unwilling and/or not able to give written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: number and severity of adverse events and serious adverse events | Baseline to 12 months post-transplant and baseline to 18 months post-transplant | To assess the safety of autologous transplantation of cryopreserved midbrain dopamine neurons into the putamen of subjects with Parkinson's disease by measuring (1) the incidence of serious adverse events at 12 months and 18 months post-transplantation and (2) the incidence and severity of all intervention emergent adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in UPDRS Part III | 18 months following transplantation | Change in Movement Disorder Society Unified Parkinson's Disease Rating Scale (UPDRS) motor (Part III) compared to the baseline. UPDRS Part III assesses motor function and is measured in both "Off" and "On" states. UPDRS Part III score range: 0-132. A lower score is associated with milder Parkinson's disease motor symptoms. |
| Change in ON time without troublesome dyskinesia | 18 months following transplantation | Change in ON time without troublesome dyskinesia is measured using a Parkinson's disease patient diary card. |
| Change in OFF time | 18 months following transplantation | Change in OFF time is measured using a Parkinson's disease patient diary card. |
| Change in baseline Levodopa Equivalent Daily Dose | 18 months following transplantation | Change in Levodopa Equivalent Daily Dose (LEDD) which measures Parkinson's medications. |
| Change in Unified Dyskinesia Rating Scale | 18 months following transplantation | The Unified Dyskinesia Rating Scale evaluates dyskinesia in patients with Parkinson's disease (range 0-104). A lower score indicates less dyskinesia. |
| Change in UPDRS Part II | 18 months following transplantation | Change in Movement Disorder Society Unified Parkinson's Disease Rating Scale (UPDRS) Part II, which assesses the motor aspects of experiences of daily living in the week prior to the visit. Score range: 0-52. A lower score is associated with less disability. |
| Change in MoCA | 18 months following transplantation | Change in Montreal Cognitive Assessment (MoCA), which measures various aspects of cognitive function. Score range 0-30. A higher score is associated with better cognitive function. |
| Change in DaTscan | Baseline to 18 months following transplantation | DaTscan (SPECT neuroimaging for dopamine transporter, DAT) imaging is performed to assess changes in dopamine neuron function in the putamen (the transplanted area of the brain). |
Countries
United States
Outcome results
None listed