REM Sleep Behavior Disorder7T-RBDNCT07790744
A Comprehensive, Multimodal Characterization of Prodromal PD in Subjects With RBD
An observational study of REM Sleep Behavior Disorder and Synucleinopathies, run by Danish Research Centre for Magnetic Resonance at 1 site in Denmark.
Trial summary
Comprehensive characterization of early-stage Parkinson's disease in patients with REM sleep behavior disorder Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder worldwide, significantly affecting quality of life and causing substantial social and economic burdens. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- REM Sleep Behavior Disorder, Synucleinopathies, Parkinson's Disease (PD)
- How many people
- 100 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Feb 2026to 31 Dec 2035
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: We have 2 groups; Subjects diagnosed with REM-sleep behaviour disorder via polysomnography Healthy, age- and gendermatched controls. Our RBD-group will be recruited via an ongoing cohort at a different site (Danish center for sleep medicine), where subjects diagnosed with RBD via polysomnography will be asked to also participate in our cohort, should they fulfill our inclusion criteria. Controls will be recruited via our own institutions webpage, as well as advertisements on other danish websites such as trialtree.dk.
Who may be able to join
- Both groups - The ability to give informed consent
- For RBD-group
- Verified REM-sleep behaviour disorder via polysonography
- No other significant neurological and psychiatric ilness
- For Healthy controls
- Age matched to RBD-group
Who cannot join
- Ferrous objects in or around the body
- Pacemaker or other implanted electronic devices
- Drug abuse unrelated to medication or alcohol abuse over a period of 6 months prior to the experiment
- Other major immunological, cardiac, neurological or neuropsychiatric disorders
- Claustrophobia
- Incapability of giving informed consent
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- Unwillingness to be informed about abnormal findings.
- Participation in clinical trials involving drug testing over a period of 6 months prior to the experiment.
- Disease symptoms leading to excessive movement inside the scanner (e.g., excessive tremor)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
Danish Research Centre for Magnetic Resonance
Hvidovre, 2650
Sune G Thomsen, MD, +4552176251, sune.gram.thomsen.01@regionh.dk
About this study
Comprehensive characterization of early-stage Parkinson's disease in patients with REM sleep behavior disorder
Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder worldwide, significantly affecting quality of life and causing substantial social and economic burdens. Currently, treatments for Parkinson's disease primarily manage symptoms through medication and lifestyle changes but cannot stop disease progression. By the time Parkinson's disease is diagnosed, substantial nerve-cell loss has already occurred in specific brain areas. Identifying early signs of PD before symptoms fully develop is essential for improving future treatment strategies.
Read more
This research project aims to deeply understand the earliest stages of Parkinson's disease by studying patients with REM sleep behavior disorder (RBD). RBD is a condition characterized by unusual movements or behaviors during dream sleep, caused by nerve-cell loss in the brainstem. Importantly, more than 80% of individuals with RBD eventually develop Parkinson's disease or related conditions, such as Dementia with Lewy Bodies or Multiple System Atrophy.
Study Goals:
Our study will examine multiple potential biomarkers (measurable indicators) that could help identify early stages of Parkinson's disease. These include:
- Brain structure changes: The Investigators will use advanced imaging methods (7-Tesla MRI) to closely examine specific brain regions known to be affected early in Parkinson's disease, particularly the substantia nigra and the locus coeruleus (LC). The LC helps regulate sleep and wakefulness, and studies have shown it is damaged in patients with RBD and Parkinson's disease. Additionally, the investigators will use specialized imaging (Pe2i-PET and MIBG-scintigraphy) to measure dopamine availability and changes in heart nerve function.
- Abnormal protein buildup (ɑ-synuclein): In Parkinson's disease, nerve-cell death is linked to abnormal clumping of a protein called ɑ-synuclein within cells. Detecting this abnormal protein buildup early might help identify who is at risk of developing Parkinson's disease. The investigators aim to explore how levels of ɑ-synuclein aggregation relate to other early signs of the disease.
- Functional changes in brain and body: Polysomnography, an overnight sleep test recording brain (EEG) and heart (ECG) activity, is the best method for diagnosing RBD. The investigators will also measure brain activity during wakefulness to further understand early changes.
- Symptoms and physical tests: Participants will undergo thorough clinical assessments, including motor and cognitive tests, as well as tests evaluating autonomic (automatic nervous system) function, such as cardiovascular responses using a tilt-table test.
Together, these extensive assessments will provide a detailed understanding of how Parkinson's disease begins and progresses. This knowledge can greatly improve early diagnosis, allowing earlier and potentially more effective treatments for individuals at high risk.
Study Design:
The investigators will recruit:
- 50 individuals diagnosed with REM sleep behavior disorder
- 50 control participants without major psychiatric or neurological disease, matched by age and gender
THe investigation team have a complete, detailed plan and will begin collecting data as soon as ethical approval is granted.
Main Hypotheses:
Although our extensive data will allow many analyses, the investigation team specifically predict:
- Individuals with RBD will show more significant damage in the locus coeruleus compared to controls.
- Greater damage in the locus coeruleus will correlate with more severe cognitive issues, sleep problems, and autonomic dysfunction.
- Cognitive issues in RBD patients might correlate with specific patterns of damage in different parts of the locus coeruleus. For example, memory problems might be linked to more damage in the front (rostral) part of this region.
Impact:
This study will significantly enhance early detection of Parkinson's disease, paving the way for personalized medical approaches and potentially more effective treatments. Conducted by a multidisciplinary team of experts in brain imaging, sleep medicine, autonomic function, and protein aggregation, this research supports Denmark's leadership in precision clinical imaging and aligns closely with hospital research strategies aimed at understanding and treating chronic diseases. Ultimately, our goal is to improve personalized patient care for Parkinson's disease in the future.
- Conditions
- REM Sleep Behavior Disorder, Synucleinopathies, Parkinson's Disease (PD), Prodromal Parkinson's Disease
- Keywords
- REM-sleep behavior disorder, Non-motor symptoms, alpha-synuclein, 7T-MRI, Parkinson's Disease, Prodromal parkinson's Disease
- Medical subject headings
- REM Sleep Behavior Disorder, Synucleinopathies, Parkinson Disease, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Control Participants | Control participants without known major psychiatric or neurological disease. | |
| RBD-subjects | Subjects diagnosed with RBD via polysomnography. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Structural disintegraiton of the Locus Coeruleus
One of the main hypotheses is that there will be a strutural pattern of disintegration in the Locus Coeruleus (LC) in our RBD-cohort when compared to controls. This will be seen as a change in neuromelanin Contrast-to-Noise-Ratio (CNR) in the LC. We expect this pattern to have a caudo-rostral gradient, as other studies have shown in subjects with Parkinson's Disease.
Measured: Baseline
Differences in neuromelanin-CNR in the Substantia Nigra pars Compacta in RBD-subjects compared to controls
As with the Locus Coeruleus, it is expected to see altered neuromelanin signal from the SNc in RBD subjects compared to controls
Measured: Baseline
Secondary outcomes (6)
Motor-task performance
The investigators expect to see group-level differences in motor-task performance with an in-house designed motor-test battery, validated before being put into use.
Measured: Baseline
Cognitive test performance
The investigators expect to see group-level differences in cognitive test performance, tested with particular tests from the CANTAB-battery, between RBD-subjects and controls, with controls performing better..
Measured: Baseline
Resting-state EEG
Preliminary data from another study (Manuscript under review) at our site has shown that the aperiodic part of resting-state EEG is able to clearly separate subjects with clinically established Parkinson's Disease from controls.
We will test whether this also holds true in the prodromal RBD-state using a short resting-state EEG recording.
Measured: Baseline
Correlation between LC and autonomic dysfunction.
Loss of LC-CNR will positively correlate with increased burden of autonomic symptoms in RBD-subjects.
Measured: Baseline
Autonomic, sympathic responses to arousing stimuli
Autonomic responses (Pupil dilation, skin conductance) to arousing stimuli will be changed in RBD-subjects compared to controls, correlating with lowered LC-CNR
Measured: Baseline
Cardiac sympathetic measures
Cardiac sympathetic nervous function, measures using MIBG-SPECT will be changed in RBD-subjects compared to controls, and correlate positively to the degree of cellular degeneration in the LC.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2026
- Study start1 Feb 2026
- Primary completion30 Jun 2028 (estimated)
- Study completion31 Dec 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for REM Sleep Behavior DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Danish Research Centre for Magnetic Resonance
- Sponsor type
- University, hospital or other
- Collaborators
- Danish Center for Sleep Medicine, University Hospital Bispebjerg and Frederiksberg
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07790744
- Sponsor's protocol ID
- 7T-RBD
- Acronym
- 7T-RBD
- Status last verified
- Mar 2026
- First submitted
- 20 Mar 2026
- Last updated
- 27 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The pseudonymized data can only be shared with a formal Data Processing Agreement and a formal approval by the Danish Data Protection agency in line with the requirements of the European General Data Protection Regulation. If complete anonymization can be achieved, individual data will be shared openly after study completion.
Publications
Miglis MG, Zitser J, Schneider L, During E, Jaradeh S, Freeman R, Gibbons CH. Cutaneous alpha-synuclein is correlated with autonomic impairment in isolated rapid eye movement sleep behavior disorder. Sleep. 2021 Dec 10;44(12):zsab172. doi: 10.1093/sleep/zsab172.
PubMed 34244806Doppler K, Jentschke HM, Schulmeyer L, Vadasz D, Janzen A, Luster M, Hoffken H, Mayer G, Brumberg J, Booij J, Musacchio T, Klebe S, Sittig-Wiegand E, Volkmann J, Sommer C, Oertel WH. Dermal phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as prodromal Parkinson's disease. Acta Neuropathol. 2017 Apr;133(4):535-545. doi: 10.1007/s00401-017-1684-z. Epub 2017 Feb 8.
PubMed 28180961Sakakibara R, Tateno F, Aiba Y, Ogata T, Kishi M, Terada H, Inaoka T, Nakatsuka T, Matsuoka K. MIBG Myocardial Scintigraphy Identifies Premotor PD/DLB During a Negative DAT Scan Period: Second Report. Mov Disord Clin Pract. 2018 Nov 9;6(1):46-50. doi: 10.1002/mdc3.12697. eCollection 2019 Jan.
PubMed 30746415Pitton Rissardo J, Fornari Caprara AL. Cardiac 123I-Metaiodobenzylguanidine (MIBG) Scintigraphy in Parkinson's Disease: A Comprehensive Review. Brain Sci. 2023 Oct 18;13(10):1471. doi: 10.3390/brainsci13101471.
PubMed 37891838Borghammer P, Van Den Berge N. Brain-First versus Gut-First Parkinson's Disease: A Hypothesis. J Parkinsons Dis. 2019;9(s2):S281-S295. doi: 10.3233/JPD-191721.
PubMed 31498132Madelung CF, Lokkegaard A, Fuglsang SA, Marques MM, Boer VO, Madsen KH, Hejl AM, Meder D, Siebner HR. High-resolution mapping of substantia nigra in Parkinson's disease using 7 tesla magnetic resonance imaging. NPJ Parkinsons Dis. 2025 May 6;11(1):113. doi: 10.1038/s41531-025-00972-7.
PubMed 40328786Madelung CF, Meder D, Fuglsang SA, Marques MM, Boer VO, Madsen KH, Petersen ET, Hejl AM, Lokkegaard A, Siebner HR. Locus Coeruleus Shows a Spatial Pattern of Structural Disintegration in Parkinson's Disease. Mov Disord. 2022 Mar;37(3):479-489. doi: 10.1002/mds.28945. Epub 2022 Feb 3.
PubMed 35114035