NCT07533799

The Swedish BioFINDER Sleep Study

BioFINDER-Sleep: Idiopathic REM-sleep Behavior Disorder & Early Parkinson's Disease

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 650 (estimated)
• Sponsor: Skane University Hospital · Academic / Other
• Sex: All
• Age: 50 Years – 100 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed description

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: 1. 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. 2. 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. 3. 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. 4. 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: The study plan to recruit early PD patients, persons with iRBD as well as healthy controls to participate in the current study. Early PD patients will be recruited from the Memory Clinic at Skåne University Hospital as well as private or public Neurology clinics within Region Skåne. Persons with iRBD will be recruited to participate in the study through advertisements in relevant media and in collaboration with private and public Sleep clinics that perform diagnostic sleep studies. Healthy controls will be recruited through advertisements. Clinical assessments: All subjects included in this study will undergo a standardized clinical assessment and fill out questionnaires as instructed by the nurse or doctor associated with the project. Symptoms of Parkinson´s disease will be evaluated using the MDS-UPDRS as well as assessment of Hoehn \& Yahr stages. Subtle motor symptoms will be examined by the use of Purdue PEG board, and alternate tapping test and the 3-m time up and go test. Questionnaires will be used to reveal the presence of non-motor symptoms, including the presence of autonomic dysfunction. Objective measurement of orthostatic hypotension is included in the clinical assessment. Hyposmia or anosmia will be quantified with Sniffin' Sticks test. The clinical assessment will be performed at baseline, and after 18, 36, 54 and 72 months to allow for detection of conversion to an established parkinsonian disorder. All follow-ups include a more in-depth evaluation of motor symptoms by a physical therapist. PET imaging: \[18F\]FE-PE2I is a highly selective imaging ligand for the assessment of dopamine transporters and provide an indirect measure of surviving dopaminergic neurons. Briefly, 185 MBq \[18F\]FE-PE2I will be injected intravenously and a static PET scan of 30 min will be performed on GE Discovery MI PET-CT cameras, starting 15 min post injection. \[18F\]FE-PE2I will be repeated at follow-up at 3 and 6 years after baseline. MIBG scintigraphy: Early and late images of the thorax will be collected for 15 minutes, 15 and 210 minutes after the administration of 110 MBq \[123I\] MIBG, respectively. Images will be collected on a SPECT-gamma camera to estimate the mean heart-uptake/mean mediastinum-uptake ratios and to estimate washout rates as the differences of mean uptake in early and late images. A low dose SPECT/CT is performed after the late images. \[123I\] MIBG scintigraphy will be repeated at follow-up at 3 and 6 years after baseline. Magnetic resonance imaging; 3 Tesla Magnetic resonance imaging (MRI) scans will be done in all study cohorts on a 3T Siemens MAGNETOM Prisma scanner. A wide variety of MRI techniques will be used to study regional brain volume (three-dimensional magnetization-prepared rapid acquisition with gradient echo (3D MPRAGE)), metabolism (MR spectroscopy (MRS)), structural and functional connectivity of different brain regions (diffusion tensor imaging (DTI) and functional MRI (fMRI)), regional blood flow (arterial spin labeling (ASL)), iron deposition (susceptibility-weighted imaging (SWI)) and the presence of small vessel disease (MPRAGE, SWI and fluid-attenuated inversion recovery (FLAIR)) as well as neuromelanin sensitive sequences that can be used as an indirect measure of dopaminergic and noradrenergic terminals. The protocol will take approximately 60 min to perform. No contrast-enhancing agent will be used. MRI will be repeated at follow-up at 3 and 6 years after baseline. Polysomnography The examination will take place during a separate study visit that includes a stay overnight at the hospital. A complete setup of the polysomnography will be performed according to the requirements of American Academy of Sleep Medicine to detect REM-sleep without atonia and compliant with the recommendations by the International REM Sleep Behavior Disorder Disorder Study Group (IRBDSG). Digital assessments of motor and cognitive performance. In a subset of study participants motor and cognitive function will be assessed using an application on a smartphone (Roche PD App). The assessments will include active tasks as well as passive tasks to evaluate both motor and cognitive performance. Cerebrospinal fluid and plasma sampling Lumbar CSF samples will be collected in all cohorts according to a standardized protocol in line with clinical standards. In short, lumbar puncture will be done between 9-12 am. 25 ml of CSF will be collected in Low Binding polypropylene tubes, which are stored on ice for 5-20 min until the CSF samples will be centrifuged (2000g, +4°C, 10 min). Thereafter, the CSF will be aliquoted in ca 1 ml portions into Low Binding polypropylene tubes followed by storage at -80°C until batch analyses. Plasma collection will be done at the same visit as the lumbar puncture. Approximately 60ml blood will be drawn into tubes containing either EDTA (5 x 6 ml tubes) or Lithium heparin (3 x 3 ml tubes) as anticoagulant. After centrifugation (2000g, +4°C, 10 min), plasma samples will be aliquoted into polypropylene tubes and stored at -80°C pending biochemical analyses. Further, EDTA-blood (2 x 6 ml) will also be obtained for genetic DNA analyses and PAX tubes (2 x 2,5 ml) will be frozen without any centrifugation or aliquoting for future RNA analyses. Fluid sampling will be repeated at follow-up at 3 and 6 years after baseline. Skin biopsy In the current study, skin biopsies are taken using a 3 mm punch biopsy methodology. A total of four biopsies will be collected from the paravertebral areas on both sides at the level of C7-C8 and an area on one of the legs, 10 cm proximal to the knee. Skin biopsy will be repeated at follow-up at 3 and 6 years after baseline, with the possibility of additional two biopsy collections if needed. Detailed motor assessments (physical therapist) The assessments mainly address level of physical activity, activity avoidance, gait- and balance problems (including falls and fear of falling) as well as dual task performance, i.e. combining a motor and a cognitive task. The data collection consists of self-administered questionnaires, interview administered questions, clinical assessments as well using objective measures (i.e. using an electronic walkway or using six wearable sensors while conducting some of the tests). Detailed motor assessment by physical therapist will be repeated at follow-up at 3 and 6 years after baseline.

Conditions

• Parkinson´s Disease
• REM Sleep Behavior Disorder (iRBD)
• Lewy Body Disease
• Synucleinopathy
• Synucleinopathies

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Dopamine transporter PET scan with [18F]FE-PE2I	Positron emission tomography (PET) imaging of dopamine transporters (DAT-PET) to quantify dopamine terminal loss.
DIAGNOSTIC_TEST	Magnetic resonance imaging (MRI)	Different MRI sequences relevant for brain imaging and with focus on dopamine associated structures of the brain.
DIAGNOSTIC_TEST	[123I] MIBG scintigraphy of the heart	MIBG scintigraphy to quantify the loss noradrenaline terminals to the heart.
DIAGNOSTIC_TEST	α-synuclein seeding amplification assays	synuclein seed amplification assays (SSAs) will be applied to cerebrospinal fluid (CSF) and skin samples to establish synuclein pathology status
DIAGNOSTIC_TEST	Polysomnography	Polysomnography to establish presence of REM-sleep behavior disorder
DIAGNOSTIC_TEST	Smell test	Sniffin' Sticks test to quantify hyposmia or anosmia.

Timeline

• Start date: 2021-10-01
• Primary completion: 2033-06-01
• Completion: 2033-06-01
• First posted: 2026-04-16
• Last updated: 2026-04-16

Locations

1 site across 1 country: Sweden