A Comprehensive, Multimodal Characterization of Prodromal PD in Subjects With RBD

NCT07790744 | Recruiting DMC

• 1 other identifier: 7T-RBD
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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:

• 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

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  Baseline

Secondary Outcomes (6)

• Motor-task performance

  Baseline

• Cognitive test performance

  Baseline

• Resting-state EEG

  Baseline

• Correlation between LC and autonomic dysfunction.

  Baseline

• Autonomic, sympathic responses to arousing stimuli

  Baseline

Other Outcomes (3)

• Longitudinal outcomes

  Through study completion, an average of 1 year

• Longitudinal outcomes

  Through study completion, an average of 1 year

• Longitudinal outcomes

  Through study completion, an average of 1 year

Study Arms (2)

Control Participants

Control participants without known major psychiatric or neurological disease.

RBD-subjects

Subjects diagnosed with RBD via polysomnography.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Danish Research Centre for Magnetic Resonance: lead
• Danish Center for Sleep Medicine: collaborator
• University Hospital Bispebjerg and Frederiksberg: collaborator

Study Sites (1)

Danish Research Centre for Magnetic Resonance

Hvidovre, 2650, Denmark

RECRUITING

Related Publications (7)

• 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.

  PMID: 34244806 BACKGROUND

• Doppler 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.

  PMID: 28180961 BACKGROUND

• Sakakibara 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.

  PMID: 30746415 BACKGROUND

• Pitton 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.

  PMID: 37891838 BACKGROUND

• Borghammer 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.

  PMID: 31498132 BACKGROUND

• Madelung 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.

  PMID: 40328786 BACKGROUND

• Madelung 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.

  PMID: 35114035 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood and skin samples testing for the occurence of alfa-synuclein pathology

MeSH Terms

Conditions

REM Sleep Behavior Disorder; Synucleinopathies; Parkinson Disease; Parkinson Disease 4, Autosomal Dominant Lewy Body

Condition Hierarchy (Ancestors)

REM Sleep Parasomnias; Parasomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders

Central Study Contacts

Sune G Thomsen, MD

CONTACT

+4552176251; sune.gram.thomsen.01@regionh.dk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2026
• First Posted: August 27, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 31, 2035
• Last Updated: August 27, 2026

Record last verified: 2026-03

Locations

DK (1)