BioFINDER-Sleep: Idiopathic REM-sleep Behavior Disorder & Early Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 650
- 试验地点
- 1
- 主要终点
- Longitudinal Changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
研究概览
简要总结
BioFINDER-Sleep study was established in 2021 and will include patients with early Parkinson´s disease (PD) and persons with iRBD to provide essential insights into the underlying mechanisms of the progressive neurodegenerative processes in central and peripheral nervous systems. Briefly polysomnography will be used to establish the presence of RBD in both the early PD cohort and in the iRBD cohort. Then, state of the art multimodal imaging techniques will be used, including, magnetic resonance imaging (MRI), positron emission tomography (PET) of the dopamine transporters (DAT-PET) to quantify dopamine terminal loss, and [123I] MIBG scintigraphy of the heart will be performed to quantify the loss noradrenaline terminals to the heart. In addition to this, synuclein seed amplification assays (SSAs) will be applied to cerebrospinal fluid (CSF) and skin samples to establish synuclein pathology status. Further, CSF and blood biomarkers will be developed that can be used to as prognostic markers. These investigations will be done in parallel to clinical assessments of motor and non-motor symptoms as well as assessment of cognitive function in a longitudinal setting.
详细描述
General aims:
The setup enables the study to test several hypotheses concerning the relation between neurodegenerative disorders and RBD. Here, the main specific aims are summarized:
- Patients with early PD will be recruited to estimate the frequency of concomitant RBD in this cohort at the time of diagnosis as well as at follow-up. The longitudinal setup enables the study to test the claim that early PD patients with concomitant RBD represent a more severe subtype of PD and whether this is reflected in blood, CSF or imaging biomarkers that are collected longitudinally.
- Persons with iRBD represent an important prodromal stage of parkinsonian disorders and are included here to study changes in clinical symptoms, blood and CSF biomarkers, imaging modalities over time to better understand the earliest symptomatic phases of these neurodegenerative disorders.
- Collected multimodal biomarkers longitudinally enables the study to investigate whether co-pathologies, like presence of Alzheimer's disease pathology, affect the clinical and biomarker trajectories over time in people with prodromal or early PD.
- Minor motor symptoms are considered a general characteristic of synucleinopathies, even in prodromal stages. However, clinical scales used in regular neurological examination may not be sensitive to subtle worsening of minor motor symptoms. Therefore, a setup will be implemented to characterize motor function in the cohort using GAITRite® and the Mobility Lab®. In addition to this, patients are asked to download an app (Roche-PD app) on their mobile phones where weekly tests of motor function and cognitive function allow for continuous monitoring of progression of symptoms. This setup will allow the study to develop clinically meaningful markers of disease.
Study plan:
Patient population:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 50 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Idiopathic RBD:
- •Polysomnography verified RBD according to AASM criteria.
- •Does not fulfill diagnostic criteria for idiopathic Parkinson´s disease.
- •Age range 50-
- •Women who are <55 years of age will be required to take a pregnancy test before participation in the PET and scintigraphy part of the study if not post-menopausal.
- •Ability to give informed consent.
- •Speaks and understands Swedish to the extent that an interpreter is not necessary for the patient to fully understand the study information and cognitive tests.
- •Early Parkinson´s disease:
- •Fulfills the diagnostic criteria for idiopathic Parkinson´s disease.
- •The PD patients will be de novo (yet without any PD treatment) or with treatment for a maximum of 3 years.
- •Age range 50-
- •Women who are <55 years of age will be required to take a pregnancy test before participation in the PET and scintigraphy part of the study if not post-menopausal.
- •Ability to give informed consent.
- •Speaks Swedish fluently as stated above. Healthy Controls
- •Age range 50-
- •Women who are <55 years of age will be required to take a pregnancy test before participation in the PET and scintigraphy part of the study if not post-menopausal.
- •No diagnosis of PD or another significant neurological disorder.
- •No diagnosis of RBD.
- •Ability to give informed consent.
- •Speaks Swedish fluently as stated above.
排除标准
- •For all groups:
- •Past history of severe or repeated concussive head injury or stroke or any significant systemic disease or unstable medical condition.
- •History of severe and unstable depression, schizophrenia, schizoaffective disorder or bipolar disorder.
- •Significant white matter microvascular disease.
- •Contraindication to MRI and PET.
- •Exclusion criteria specific for early Parkinson´s disease:
- •Normal dopamine transporter ([18F]FE-PE2I) scan.
研究组 & 干预措施
Idiopathic REM-sleep Behavior Disorder (iRBD)
200 individuals with iRBD will be recruited through advertisement or due to being under clinical investigation for the condition at any clinic in the county of Skåne, Sweden.
干预措施: Dopamine transporter PET scan with [18F]FE-PE2I (Diagnostic Test)
Idiopathic REM-sleep Behavior Disorder (iRBD)
200 individuals with iRBD will be recruited through advertisement or due to being under clinical investigation for the condition at any clinic in the county of Skåne, Sweden.
干预措施: Magnetic resonance imaging (MRI) (Diagnostic Test)
Idiopathic REM-sleep Behavior Disorder (iRBD)
200 individuals with iRBD will be recruited through advertisement or due to being under clinical investigation for the condition at any clinic in the county of Skåne, Sweden.
干预措施: [123I] MIBG scintigraphy of the heart (Diagnostic Test)
Idiopathic REM-sleep Behavior Disorder (iRBD)
200 individuals with iRBD will be recruited through advertisement or due to being under clinical investigation for the condition at any clinic in the county of Skåne, Sweden.
干预措施: α-synuclein seeding amplification assays (Diagnostic Test)
Idiopathic REM-sleep Behavior Disorder (iRBD)
200 individuals with iRBD will be recruited through advertisement or due to being under clinical investigation for the condition at any clinic in the county of Skåne, Sweden.
干预措施: Polysomnography (Diagnostic Test)
Idiopathic REM-sleep Behavior Disorder (iRBD)
200 individuals with iRBD will be recruited through advertisement or due to being under clinical investigation for the condition at any clinic in the county of Skåne, Sweden.
干预措施: Smell test (Diagnostic Test)
Early Parkinson´s disease
200 patients with early Parkinson's disease will be recruited from the Neurology clinic at Skåne University Hospital and in addition other Neurology clinics in the county of Skåne, Sweden.
干预措施: Magnetic resonance imaging (MRI) (Diagnostic Test)
Early Parkinson´s disease
200 patients with early Parkinson's disease will be recruited from the Neurology clinic at Skåne University Hospital and in addition other Neurology clinics in the county of Skåne, Sweden.
干预措施: Dopamine transporter PET scan with [18F]FE-PE2I (Diagnostic Test)
Early Parkinson´s disease
200 patients with early Parkinson's disease will be recruited from the Neurology clinic at Skåne University Hospital and in addition other Neurology clinics in the county of Skåne, Sweden.
干预措施: [123I] MIBG scintigraphy of the heart (Diagnostic Test)
Early Parkinson´s disease
200 patients with early Parkinson's disease will be recruited from the Neurology clinic at Skåne University Hospital and in addition other Neurology clinics in the county of Skåne, Sweden.
干预措施: α-synuclein seeding amplification assays (Diagnostic Test)
Early Parkinson´s disease
200 patients with early Parkinson's disease will be recruited from the Neurology clinic at Skåne University Hospital and in addition other Neurology clinics in the county of Skåne, Sweden.
干预措施: Polysomnography (Diagnostic Test)
Early Parkinson´s disease
200 patients with early Parkinson's disease will be recruited from the Neurology clinic at Skåne University Hospital and in addition other Neurology clinics in the county of Skåne, Sweden.
干预措施: Smell test (Diagnostic Test)
Healthy controls
250 healthy controls will be recruited through advertisement and by personal invitation by mail.
干预措施: Dopamine transporter PET scan with [18F]FE-PE2I (Diagnostic Test)
Healthy controls
250 healthy controls will be recruited through advertisement and by personal invitation by mail.
干预措施: Magnetic resonance imaging (MRI) (Diagnostic Test)
Healthy controls
250 healthy controls will be recruited through advertisement and by personal invitation by mail.
干预措施: [123I] MIBG scintigraphy of the heart (Diagnostic Test)
Healthy controls
250 healthy controls will be recruited through advertisement and by personal invitation by mail.
干预措施: α-synuclein seeding amplification assays (Diagnostic Test)
Healthy controls
250 healthy controls will be recruited through advertisement and by personal invitation by mail.
干预措施: Polysomnography (Diagnostic Test)
Healthy controls
250 healthy controls will be recruited through advertisement and by personal invitation by mail.
干预措施: Smell test (Diagnostic Test)
结局指标
主要结局
Longitudinal Changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
时间窗: From baseline to the end of follow-up 72 months later
Will be evaluated at each follow-up visit every 18 months. The MDS-UPDRS is a clinical rating tool used to assess both motor and non-motor symptoms of Parkinson's disease, as well as their effect on activities of daily living. It is divided into 4 subparts and cotains questions and clinical evaluations. Part 1 and 2 each contain 13 questions. Each question is scored from 0 to 4, where higher scores indicate more severe symptoms. The maximum score for each of these parts is 52. Part 3 is a clinical examination of motor symptoms. It includes 33 items, also scored from 0 to 4. The maximum score for this section is 132. Part 4 assesses motor complications and contains 6 items, scored from 0 to 4. The maximum score for this part is 24"
Longitudinal Changes in Mini-Mental State Examination (MMSE)
时间窗: From baseline to the end of follow-up 72 months later
Will be evaluated at each follow-up visit every 18 months. MMSE screens for cognitive impairment and score from 0-30 points where higher points indicate better cognitive function.
Time to phenoconversion from iRBD to manifest parkinsonian disorders
时间窗: From baseline to the end of follow-up 72 months later
Time to phenoconversion from diagnosis of iRBD to manifestation of a parkinsonian disorders according to clinical diagnostic criteria as evaluated at consensus group decision at the last visit.
次要结局
- Correlation between objective testing of motor function by clinician and digital biomarkers of motor function(From baseline to the end of follow-up 72 months later)
- Correlation of changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) to imaging and fluid biomarkers(From baseline to the end of follow-up 72 months later)
- Correlation of changes in Mini-Mental State Examination (MMSE) to imaging and fluid biomarkers(From baseline to the end of follow-up 72 months later.)
研究者
Erik Stomrud
Principal Investigator
Skane University Hospital