The Parkinson's Progression Markers Initiative (PPMI)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 952
- 试验地点
- 34
- 主要终点
- Mean Rates of Change
研究概览
简要总结
This is a observational, multi-center study to assess progression of clinical features, imaging and biologic biomarkers in Parkinson disease (PD) patients compared to healthy controls (HC) and in PD patient subtypes.
The primary objective of this study is to identify clinical, imaging and biologic markers of PD progression for use in clinical trials of disease-modifying therapies.
详细描述
Amendment 14 - 26-Mar-2018 Revised to reflect the implementation of PPMI Wearables and Sensor Study Companion Protocol
Amendment 13 - 20-Nov-2017 Extension of study duration until 2023 for all cohorts (except Genetic Registry).
Amendment 12 - 01-Jun-2017 Planned date of trial extended to September 30, 2020 Ceasing new enrollments into the Genetic Registry for LRRK2 and GBA subjects Added Sensor - PPMI Companion Study Allow for consent to share contact information with FOUND team at any visit. Incorporation of Parkinson's Disease Risk Factor Questionnaire (PD-RFQ) into FOUND.
Amendment 11 - 01-Apr-2016 Added the collection of peripheral blood mononuclear cells (PBMC) from blood samples at interim visits.
Addition of PPMI Pathology Core/PPMI Brain and Tissue Bank Addition of Gait Assessment Companion Study (Select PPMI sites - Genetic Cohort only) Testing for additional GBA mutations - previously testing involved testing only for the GBA N370S mutation; however, going forward, testing will include tests for additional GBA mutations that are identified as being associated with certain ancestry.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Parkinson Disease (PD) Subjects:
- •A diagnosis of Parkinson disease for 2 years or less at Screening.
- •Confirmation from imaging core that screening DAT scan is consistent with dopamine transporter deficit, or if applicable a VMAT-2 PET scan consistent with vesicular monoamine transporter deficit.
- •Not expected to require PD medication with at least 6 months from Baseline.
- •Male or female age 30 years or older at time of PD diagnosis.
- •Healthy Control (HC) Subjects:
- •Male or female age 30 years or older at Screening.
排除标准
- •Parkinson Disease (PD) Subjects:
- •Currently taking levodopa, dopamine agonists, MAO-B inhibitors, amantadine or other PD medication.
- •Has taken levodopa, dopamine agonists, MAO-B inhibitors or amantadine within 60 days of Baseline.
- •Has taken levodopa or dopamine agonists prior to Baseline for more than a total of 60 days.
- •Received any of the following drugs that might interfere with DAT imaging: Neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative, within 6 months of Screening.
- •Current treatment with anticoagulants (e.g., coumadin, heparin) that might preclude safe completion of the lumbar puncture.
- •If applicable, currently taking medications that are known to cause QT-prolongation, or are currently taking tetrabenazine (TBZ or amphetamine type medications.
- •Condition that precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia.
- •Use of investigational drugs within 60 days prior to Baseline (dietary supplements taken outside of a clinical trial are not exclusionary, e.g., coenzyme Q10).
- •Healthy Control (HC) Subjects:
- •Current or active neurological disorder.
- •First degree relative with idiopathic PD (parent, sibling, child).
- •MoCA score <
- •Received any of the following drugs that might interfere with DAT imaging: Neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative, within 6 months of Screening.
- •If applicable, currently taking medications that are known to cause QT-prolongation, or are currently taking tetrabenazine (TBZ) or amphetamine type medications.
- •Current treatment with anticoagulants (e.g., coumadin, heparin) that might preclude safe completion of the lumbar puncture.
- •Condition that precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia.
- •Use of other investigational drugs within 60 days prior to baseline (dietary supplements taken outside of a clinical trial are not exclusionary, e.g., coenzyme Q10).
- •SWEDD Subjects:
- •All PD criteria apply, as above, except a SWEDD subject must have confirmation from imaging core that screening dopamine transporter SPECT scan shows no evidence of dopamine transporter deficit or if applicable a VMAT-2 PET scan shows no evidence of vesicular monoamine transporter deficit.
- •Prodromal Subjects:
- •Inclusion Criteria (Prodromal Subjects) 4.2.7.
- •Subjects must have at least one of the following characteristics:
- •Male or female age 60 years or older
- •Confirmation from olfactory core that olfaction as determined by UPSIT is at or below the 10th percentile by age and gender
- •REM Behavior Disorder (RBD):
- •Male or female age 60 years or older
- •Confirmation from sleep core that subject's Polysomnography (PSG) meets criteria for RBD
- •Male or female age 60 years or older
- •Written confirmation or documentation from testing facility that the individual is LRRK2 mutation positive 4.2.7.
- •Confirmation from imaging core that screening dopamine transporter SPECT scan is read as eligible (see below). About 80 subjects will have a range of DAT deficit similar to subjects with early PD (mild to moderate DAT deficit). About 20 subjects will be selected with no DAT deficit or minimal DAT deficit similar in age, gender, and risk profile to those with mild to moderate DAT deficit. 4.2.7.
- •Ability to provide written informed consent in accordance with Good Clinical Practice (GCP), International Conference on Harmonization (ICH), and local regulations. 4.2.7.
- •Willing and able to comply with scheduled visits, required study procedures and laboratory tests. 4.2.7.
- •Women may not be pregnant, lactating or planning pregnancy during the course of the study. Includes a negative urine pregnancy test on day of screening scan prior to injection (DaTSCAN).
- •Exclusion Criteria (Prodromal Subjects)
- •Current or active clinically significant neurological disorder or psychiatric disorder (in the opinion of the Investigator).
- •GDS score greater than or equal to 10 (GDS score of 5 - 9 requires Investigator discretion to enter study).
- •STAI Form Y-1 greater than or equal to 54 requires Investigator discretion to enter study.
- •A clinical diagnosis of dementia63 as determined by the investigator (Appendix 1).
- •A clinical diagnosis of Parkinson disease at the Screening visit as determined by the Investigator.
- •Received any of the following drugs that might interfere with dopamine transporter SPECT imaging: Neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative, within 6 months of Screening.
- •Current treatment with anticoagulants (e.g., coumadin, heparin) that might preclude safe completion of the lumbar puncture.
- •Condition that precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia.
- •Any other medical or psychiatric condition or lab abnormality, which in the opinion of the investigator might preclude participation.
- •Use of investigational drugs or devices within 60 days prior to Baseline (dietary supplements taken outside of a clinical trial are not exclusionary, e.g., coenzyme Q10).
- •Previously obtained MRI scan with evidence of clinically significant neurological disorder (in the opinion of the Investigator).
- •Genetic Cohort: Parkinson Disease Subjects - Inclusion:
- •Patients must have at least two of the following: resting tremor, bradykinesia, rigidity (must have either resting remor or bradykinesia) or either asymmetric resting tremor or asymmetric bradykinesia.
- •A diagnosis of Parkinson Disease for 7 years or less at screening.
- •Hoehn and Yahr state <4 at baseline
- 另有 20 项未显示
研究组 & 干预措施
Datscan SPECT Imaging
Subjects will b injected with 3-5 mCi of dopamine transporter. Within a 4 hour (+/- 30 minutes) window following the injection, subjects will undergo SPECT imaging on the camera.
干预措施: DaTscan (Drug)
结局指标
主要结局
Mean Rates of Change
时间窗: Baseline to 156 months
The mean rates of change and the variability around the mean of clinical, imaging and biomic outcomes in early PD patients, and where appropriate the comparison of these rates between PD patient subsets and between various subsets (including, but not limited to: PD vs. healthy subjects, PD vs. SWEDD, PD vs. prodromal, PD with and without LRRK2, GBA or SNCA mutation, unaffected LRRK2, GBA or SNCA mutation carriers vs. healthy controls) at study intervals ranging from 3 months to 36 months. Specific examples of outcomes include MDS-UPDRS, dopamine transporter imaging striatal uptake, vesicular monoamine transporter type-2 uptake, and serum and CSF alpha-synuclein. PD patient subsets may be defined by baseline assessments, genetic mutations, progression milestones and/or rate of clinical, imaging, or biomic change.
次要结局
- Comparison between Rates of Change(Study intervals ranging from 3 months to 156 months)
- Predictive Value(Baseline to 156 months)
- Prevalence of measures of clinical, imaging and biomic outcomes in various subsets ((study intervals ranging from baseline to 156 months.)
- To examine the proportion of SWEDD subjects that have a change in their clinical management at 24 months(Baseline to 156 Months)
- Exploratory Analysis(Baseline to 156 months)
研究者
Ken Marek, MD
Study Chair
Michael J. Fox Foundation for Parkinson's Research