NCT04506073已完成2 期
A Randomized, Double-blind, Placebo-controlled Trial of Allogeneic Bone Marrow-derived Mesenchymal Stem Cells as a Disease-modifying Therapy for Idiopathic Parkinson's Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mya Schiess
- 入组人数
- 45
- 试验地点
- 2
- 主要终点
- Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
研究概览
简要总结
The purpose of this study is to select the safest and most effective number of repeat doses of allogeneic bone marrow-derived mesenchymal stem cell (MSC) infusions to slow the progression of Parkinson's disease (PD).
详细描述
Single site phase IIa study of allogeneic MSC in a double blind randomized control trial as disease modifying therapy for PD. The design includes three treatment arms with 45 patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 50 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Parkinson's disease by the UK brain bank criteria including the presence of 2 cardinal signs of PD plus bradykinesia.
- •Mild microsomia to anosmia.
- •A modified Hoehn and Yahr stage of 3 or less.
- •Date of diagnosis of PD between 3 to 10 years
- •Robust response to dopaminergic therapy.
排除标准
- •Atypical, vascular, or drug-induced Parkinsonism.
- •An atypical DAT scan or MRI supporting an alternative explanation for PD symptoms.
- •Patient not on levodopa containing medications.
- •Clinical features of psychosis or refractory hallucinations.
- •A Montreal Cognitive Assessment (MoCA) score of less than
- •Uncontrolled seizure disorder.
- •Abnormal Kidney and liver function.
- •Presence of clinically refractory orthostatic hypotension at the screening or baseline visit.
- •Body mass index of greater than or equal to
- •Cardiac disease: History of congestive heart failure, clinically significant bradycardia, presence of 2nd, or 3rd-degree atrioventricular block.
- •Pulmonary disease: COPD with oxygen-requirement at rest or with ambulation; or moderate to severe asthma.
- •Active malignancy or diagnosis of malignancy within 5 years prior to the start of screening
- •Any current suicidal ideation or behaviors.
- •Any diagnosis of autoimmune disease or immunocompromised state
- •History of medium or large size vessel cerebrovascular accidents.
- •History of traumatic brain injury with loss of consciousness and residual neurologic symptoms.
- •Major surgery within the previous 3 months or planned in the ensuing 6 months.
- •History of use of an investigational drug within 90 days prior to the screening visit.
- •History of brain surgery for PD.
- •Substance abuse disorder.
- •Active anticoagulation treatment and/or abnormal INR.
研究组 & 干预措施
Placebo
Placebo Comparator
3 placebo doses administered every 4 months.
干预措施: Placebo (Drug)
Mesenchymal Stem Cells
Experimental
3 infusions of 10 X 10^6 MSC/kg administered every 4 months.
干预措施: Mesenchymal Stem Cells (Drug)
Mesenchymal Stem Cells and Placebo
Experimental
2 infusions of 10 X 10^6 MSC/kg and 1 placebo infusion, all doses administered 4 months apart.
干预措施: Mesenchymal Stem Cells (Drug)
Mesenchymal Stem Cells and Placebo
Experimental
2 infusions of 10 X 10^6 MSC/kg and 1 placebo infusion, all doses administered 4 months apart.
干预措施: Placebo (Drug)
结局指标
主要结局
Safest number of effective doses of MSC as measured by the Part III of the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) scale
时间窗: Week 78 follow-up
Bayesian Mean Estimate of the Proportion of Participants Achieving a ≥5-point Improvement on MDS-UPDRS Part III From Screening to Week 62, Compared Between Each Active MSC Dose Arm and Placebo
时间窗: From Baseline to Week 62
The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III assesses motor symptoms of Parkinson's disease. . A responder was defined as a participant achieving a ≥5-point improvement (decrease of at least 5 points from screening) at Week 62. Reported are the Bayesian mean estimates of the proportion of participants achieving this response. The 95% confidence interval represents the Bayesian 95% credible interval.
次要结局
- Quality of life as measured by the modified Schwab and England activities of daily living scale (ADL)(Baseline,week 7,week 20,week 29,week 39,week 52,week 78)
- Quality of life as measured by the Parkinson's Disease Questionnaire 39 (PDQ-39)(Baseline,week 7,week 20,week 29,week 39,week 52,week 78)
- Quality of life as measured by the EuroQol- 5 Dimension (EQ-5D)(Baseline,week 7,week 20,week 29,week 39,week 52,week 78)
- Cognitive function as measured by the the change in Montreal Cognitive Assessment (MoCA)(Baseline,week 29,week 78)
- Global measurement of disability as measured by the change in the screening "Off" modified Hoehn and Yahr (H&Y)(Baseline,week 7,week 20,week 29,week 39,week 52,week 78)
- Non-motor symtoms as measured by the The University of Pennsylvania Smell Identification Test (UPSIT- 40 odor test booklet).(Baseline,week 29,week 78)
- Behavioral changes as measured by the Columbia Suicide Severity Rating Scale (C-SSRS)(Baseline,week 7,week 20,week 29,week 39,week 52,week 78)
- Measurement of putative paracrine mechanism of MSCs as measured by concentration of cytokines in patient blood sample.(Baseline,week 7,week 20,week 29,week 39,week 78)
- Measurement of putative paracrine mechanism of MSCs as measured by concentration of chemokines in patient blood sample.(Baseline,week 7,week 20,week 29,week 39,week 78)
- Measurement of putative paracrine mechanism of MSCs as measured by concentration of growth factors(Baseline,week 7,week 20,week 29,week 39,week 78)
- Measurement of putative paracrine mechanism of MSCs as measured by concentration of neurotransmitters(Baseline,week 7,week 20,week 29,week 39,week 78)
- Measurement of putative paracrine mechanism of MSCs as measured by alpha-synuclein oligomers in the blood (serum or plasma)(Basleline,week 29,week 39,week 78)
- Measurement of putative paracrine mechanism of MSCs as measured by alpha-synuclein oligomers in the cerebral spinal fluid(Baseline,week 39)
- Safety and tolerability as measured by serious adverse reactions.(Baseline,week 7,week 20,week 29,week 39,week 78)
- Safety and tolerability as measured by immunologic responses.(Baseline,week 7,week 20,week 29,week 39,week 78)
- Motor function as measured by the Timed-Up-and-Go (TUG) scale(Baseline,week 7,week 20,week 29,week 39,week 52,week 78)
- Behavioral changes as measured by the Geriatric Depression Scale-Short Form (GDS-SF)(Baseline,week 7,week 20,week 29,week 39,week 52,week 78)
- Behavioral changes as measured by the Parkinson Anxiety Scale (PAS)(Baseline,week 7,week 20,week 29,week 39,week 52,week 78)
- Measurement of putative paracrine mechanism of MSCs using neuroimaging(Baseline,week 29,week 78)
- Number of Participants With New-onset Organ Failure(Baseline through week 88)
- Number of Participants Developing Donor-Specific Anti-HLA Antibodies(Baseline through week 88)
- Motor Function as Measured by the Timed-Up-and-Go (TUG) Scale(Baseline, Week 9, Week 27, Week 40, Week 62, Week 88)
- Number of Participants With Lifetime Suicidal Ideation (C-SSRS)(Baseline)
- Parkinson's Disease Severity as Assessed by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score(Baseline, Week 9, Week 27, Week 40, Week 62, Week 88)
- Motor Symptoms of Parkinson's Disease as Assessed by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Motor Examination Score(Baseline, Week 9, Week 27, Week 40, Week 62, Week 88)
- Global Measurement of Disability as Measured by the Change in the Screening "Off" Modified Hoehn and Yahr (H&Y)(Baseline, Week 9, Week 27, Week 40, Week 62, Week 88)
- Quality of Life as Measured by the Modified Schwab and England Activities of Daily Living Scale (ADL)(Baseline, Week 9, Week 27, Week 40, Week 62, Week 88)
- Quality of Life as Measured by the Parkinson's Disease Questionnaire-39 (PDQ-39)(Baseline, Week 9, Week 27, Week 40, Week 62, Week 88)
- Quality of Life as Measured by the EuroQol- 5 Dimension (EQ-5D) Index Score(Baseline, Week 9, Week 27, Week 40, Week 62, Week 88)
- Non- Motor Symptoms as Measured by the Non-Motor Symptoms Questionnaire (NMSQ)(Baseline, Week 9, Week 27, Week 40, Week 62, Week 88)
- Olfactory Function as Assessed by the University of Pennsylvania Smell Identification Test (UPSIT-40) Score(Baseline, Week 49, Week 88)
- Cognitive Function as Measured by the Montreal Cognitive Assessment (MoCA)(Baseline, Week 49, Week 88)
- Anxiety as Assessed by the Parkinson Anxiety Scale (PAS) Score(Baseline, Week 9, Week 27, Week 40, Week 62, Week 88)
- Depressive Symptoms as Assessed by the Geriatric Depression Scale-Short Form (GDS-SF) Score(Baseline, Week 9, Week 27, Week 40, Week 62, Week 88)
- Number of Participants Reporting Suicidal Ideation Since Last Visit(Week 9, Week 27, Week 49, Week 62, Week 88)
研究者
Mya Schiess
Professor and Adriana Blood Chair in Neurology
The University of Texas Health Science Center, Houston
研究点 (2)
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