The Parkinson's Progression Markers Initiative (PPMI) Clinical - Establishing a Deeply Phenotyped PD Cohort
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 4,500
- 试验地点
- 90
- 主要终点
- Comparison between Rates of Change
研究概览
简要总结
The Parkinson Progression Marker Initiative (PPMI) is a longitudinal, observational, multi-center natural history study to assess progression of clinical features, digital outcomes, and imaging, biologic and genetic markers of Parkinson's disease (PD) progression in study participants with manifest PD, prodromal PD, and healthy controls.
The overall goal of PPMI is to identify markers of disease progression for use in clinical trials of therapies to reduce progression of PD disability.
详细描述
PPMI is a broad program, expanding the goals of the original PPMI study, that includes this PPMI Clinical protocol, as well as other program initiatives such as the PPMI Remote, PPMI Digital App and PPMI Online protocols. Participants in PPMI may be asked to be enrolled in other PPMI program protocols, but depending on their method of recruitment, participants may be enrolled sequentially in varying order, as appropriate. PPMI participants may also be asked to participate in additional PPMI program initiatives (as they are developed), which may only involve a subset of PPMI participants based on their cohort designation and/or site location.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Other
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •7.1 Healthy Controls (HC) Note: Active Healthy controls previously enrolled in PPMI do not require re-assessment of eligibility criteria listed below for enrollment in PPMI Clinical. Active participants do need to be able to provide informed consent for PPMI Clinical participation (includes use of a designated research proxy).
- •7.1.1 Inclusion Criteria (HC)
- •Male or female age 57 years or older at Screening visit.
- •Individuals taking any of the following drugs: alpha methyldopa, methylphenidate, amphetamine derivatives or modafinil, must be willing and medically able to hold the medication for at least 5 half-lives before SPECT imaging.
- •Confirmation that participant is eligible based on Screening SPECT imaging.
- •Able to provide informed consent.
- •Either is male, or is female and meets additional criteria below, as applicable:
- •Female of childbearing potential who is not pregnant, lactating, or planning pregnancy during the study and has a negative pregnancy test on day of Screening SPECT imaging test prior to injection of DaTscanTM.
排除标准
- •First degree relative with PD (i.e., biologic parent, sibling, child).
- •Current or active clinically significant neurological disorder (in the opinion of the Investigator).
- •Previously obtained MRI scan with evidence of clinically significant neurological disorder (in the opinion of the Investigator).
- •Received any of the following drugs: dopamine receptor blockers (neuroleptics), metoclopramide and reserpine within 6 months of Screening visit.
- •Current treatment with anticoagulants (e.g., coumadin, heparin, oral thrombin inhibitors) 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.
- •Any other reason that, in the opinion of the investigator, would render the participant unsuitable for study enrollment.
- •7.2 Parkinson's Disease (PD) Note: Active PD participants previously enrolled in PPMI do not require re-assessment of eligibility criteria listed below for enrollment in PPMI Clinical. Active participants do need to be able to provide informed consent for PPMI Clinical participation (includes use of a designated research proxy).
- •7.2.1 Inclusion Criteria (PD)
- •Male or female age 30 years or older at Screening Visit.
- •A diagnosis of Parkinson's disease for 2 years or less at Screening Visit.
- •Not expected to require PD medication within at least 6 months from Baseline.
- •Patients must have at least two of the following: resting tremor, bradykinesia, rigidity (must have either resting tremor or bradykinesia); OR either asymmetric resting tremor or asymmetric bradykinesia.
- •Hoehn and Yahr stage I or II at Baseline.
- •Individuals taking any of the following drugs: alpha methyldopa, methylphenidate, amphetamine derivatives or modafinil, must be willing and medically able to hold the medication for at least 5 half-lives before SPECT imaging.
- •Confirmation that participant is eligible based on Screening SPECT imaging.
- •Able to provide informed consent.
- •Either is male, or is female and meets additional criteria below, as applicable:
- •Female of childbearing potential who is not pregnant, lactating, or planning pregnancy during the study and has a negative pregnancy test on day of Screening SPECT imaging test prior to injection of DaTscanTM.
- •7.2.2 Exclusion Criteria (PD)
- •Currently taking levodopa, dopamine agonists, MAO-B inhibitors, amantadine or another PD medication, except for low-dose treatment of restless leg syndrome (with permission of medical monitor).
- •Has taken levodopa, dopamine agonists, MAO-B inhibitors or amantadine within 60 days of Baseline visit.
- •Has taken levodopa or dopamine agonists prior to Baseline visit for more than a total of 90 days.
- •Atypical PD syndromes due to either drugs (e.g., metoclopramide, flunarizine, neuroleptics) or metabolic disorders (e.g., Wilson's disease), encephalitis, or degenerative diseases (e.g., progressive supranuclear palsy).
- •A clinical diagnosis of dementia as determined by the investigator.
- •Previously obtained MRI scan with evidence of clinically significant neurological disorder (in the opinion of the Investigator).
- •Received any of the following drugs: dopamine receptor blockers (neuroleptics), metoclopramide and reserpine within 6 months of Screening visit.
- •Current treatment with anticoagulants (e.g., coumadin, heparin, oral thrombin inhibitors) 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.
- •Any other reason that, in the opinion of the investigator, would render the participant unsuitable for study enrollment.
- •7.3 Parkinson's Disease (PD) with LRRK2 or GBA variant Note: Active PD participants previously enrolled in PPMI do not require re-assessment of eligibility criteria listed below for enrollment in PPMI Clinical. Active participants do need to be able to provide informed consent for PPMI Clinical participation (includes use of a designated research proxy).
- •7.3.1 Inclusion Criteria (PD ¬- LRRK2 or GBA)
- •Male or female age 30 years or older at Screening Visit.
- •A diagnosis of Parkinson's disease for 2 years or less at Screening Visit.
- •Patients must have at least two of the following: resting tremor, bradykinesia, rigidity (must have either resting tremor or bradykinesia); OR either asymmetric resting tremor or asymmetric bradykinesia.
- •Hoehn and Yahr stage I or II at Baseline.
- •Confirmation of causative LRRK2 or GBA (willingness to undergo genetic testing as part of genetic screening and be informed of genetic testing results, or approved documentation of prior genetic testing results).
- •Individuals taking any of the following drugs: alpha methyldopa, methylphenidate, amphetamine derivatives or modafinil, must be willing and medically able to hold the medication for at least 5 half-lives before SPECT imaging.
- •Confirmation that participant is eligible based on Screening SPECT imaging.
- •Able to provide informed consent.
- •Either is male, or is female and meets additional criteria below, as applicable:
- •Female of childbearing potential who is not pregnant, lactating, or planning pregnancy during the study and has a negative pregnancy test on day of Screening SPECT imaging test prior to injection of DaTscanTM.
- •7.3.2 Exclusion Criteria (PD - LRRK2 or GBA)
- •Received any of the following drugs: dopamine receptor blockers (neuroleptics), metoclopramide and reserpine within 6 months of Screening visit.
- •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.
- •Any other reason that, in the opinion of the investigator, would render the participant unsuitable for study enrollment.
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研究组 & 干预措施
Clinical Observation
In PPMI Clinical up to 4,500 participants will be enrolled and followed longitudinally once identified, over the course of 5-8 years.
结局指标
主要结局
Comparison between Rates of Change
时间窗: Study intervals ranging from 3 months to 156 months
Use clinical and biological data to estimate the mean rates of change and the variability around the mean of clinical, digital, imaging, biological and genetic outcomes in study participants with PD diagnosis (including patients with a LRRK2, GBA, SNCA or rare genetic variants (such as Parkin or Pink1) and individuals with prodromal Parkinson's disease (including individuals with REM sleep behavior disorder (RBD)), olfactory loss, LRRK2, GBA, SNCA or rare genetic variants (such as Parkin or Pink1) and/or other risk factors for PD with and without dopamine transporter (DAT) deficit and in healthy participants.
Establish the probability of phenoconversion to PD
时间窗: study intervals ranging from baseline to 156 months.
Evaluate the probability of phenoconversion to PD for individuals with prodromal PD enrolled in the prodromal cohorts (including individuals with RBD, olfactory loss, a LRRK2, GBA, SNCA or rare genetic variants (such as Parkin or Pink1) and/ or other risk factors for PD with and without DAT deficit).
Establish standardized protocols for acquisition, transfer and analysis of clinical, digital, imaging, biologic and genetic data that can be used by the PD research community.
时间窗: Baseline to 156 months
This protocol will build on the existing PPMI infrastructure
Comprehensive and uniformly acquired dataset
时间窗: Baseline to 156 months
Develop a comprehensive and uniformly acquired clinical, digital and imaging dataset and repository of biological and genetic samples that would be available to the PD research community to test hypotheses of the underlying molecular pathobiology of PD, enable modeling of PD progression to identify clinical and/or data driven PD progression sub-sets, and inform studies testing PD therapeutics (for examples, clinical trials targeting synuclein, LRRK2, GBA as well as other targets)
Prevalence of measures of clinical, imaging and biomic outcomes in various subsets
时间窗: study intervals ranging from baseline to 156 months.
Confirm existing and identify novel clinical, digital, imaging, biologic and genetic PD progression markers to identify quantitative individual measures or combinations of measures that demonstrate optimum interval change in study participants with PD diagnosis (including patients with a LRRK2, GBA, SNCA or rare genetic variants (such as Parkin or Pink1)) and individuals with prodromal Parkinson's disease (including individuals with RBD, olfactory loss, a LRRK2, GBA, SNCA or rare genetic variants (such as Parkin or Pink1) and/or other risk factors for PD with and without DAT deficit in comparison to healthy controls or in sub-sets of study participants with PD diagnosis or prodromal PD defined by baseline assessments, progression milestones and/or rate of clinical, digital, imaging, biologic and genetic change, or other measures.
次要结局
未报告次要终点
研究者
Ken Marek, MD
Protocol Co- Principal Investigator
Institute for Neurodegenerative Disorders