A Phase 1 Clinical Trial of Autologous iPSC-Derived Dopamine Neuron Transplantation for Parkinson's Disease
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Safety: number and severity of adverse events and serious adverse events
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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:
- •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
- •Severe arrhythmia
- •History of cardiovascular surgery (cardiac, vascular stent surgery, angioplasty);
- •History of stroke or transient ischemic attack
- •History of subarachnoid hemorrhage
- •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.
研究组 & 干预措施
Autologous midbrain dopamine neurons
干预措施: Autologous midbrain dopamine neurons (Biological)
结局指标
主要结局
Safety: number and severity of adverse events and serious adverse events
时间窗: 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.
次要结局
- Change in UPDRS Part III(18 months following transplantation)
- Change in MoCA(18 months following transplantation)
- Change in OFF time(18 months following transplantation)
- Change in Unified Dyskinesia Rating Scale(18 months following transplantation)
- Change in DaTscan(Baseline to 18 months following transplantation)
- Change in ON time without troublesome dyskinesia(18 months following transplantation)
- Change in baseline Levodopa Equivalent Daily Dose(18 months following transplantation)
- Change in UPDRS Part II(18 months following transplantation)
研究者
Penelope J. Hallett, Ph.D.
Associate Professor
Mclean Hospital