Identification of Prodromal Neurodegeneration in Serotonergic-Induced REM Sleep Behavior Disorder
NCT Number: NCT06467461
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Dementia With Lewy Bodies|Parkinson Disease|REM Sleep Behavior Disorder
Interventions: DIAGNOSTIC_TEST: Skin biopsy|DIAGNOSTIC_TEST: Speech testing|DIAGNOSTIC_TEST: Ultra high field 7T MRI
Sponsor: University of Minnesota
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 60
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: BASIC_SCIENCE
Start Date: 2024-02-08
Completion Date: 2028-12-30
Locations: University of Minnesota, Minneapolis, Minnesota, 55455, United States

Summary:
This project will test the hypotheses that people with 5-HT RBD have systemic alpha- synuclein pathology, prodromal DLB signs, and brainstem lesions in regions that control REM sleep. AIM 1 will seek to detect abnormally phosphorylated alpha- synuclein aggregates on targeted skin biopsy in a cohort of people with 5-HT RBD and matched controls (taking SSRIs but without RBD). Aim 2 will use ultra-high field MRI at 7T to examine the pontine region of the coeruleus/subcoeruleus complex for evidence of neurodegeneration as well as segment and parcellate REM sleep related neuronal structures. Aim 3 will test for speech deficits. While these aims are independent we suspect that the severity of autonomic, speech and cognitive deficits will correlate with loss of neuromelanin signal on MRI and pathology on skin biopsy.

The investigation is a longitudinal designed study to examine histopathology, neuroimaging changes and speech function from baseline (Time 1) to a follow-up after 30 months (Time 2). A total of 60 individuals, 30 with 5-HT RBD and 30 controls, will be recruited at Time 1, brought back at Time 2, and tested across all Aims at both study visits.

Primary Outcome Measures: Phosphorylated alpha synuclein deposits on skin biopsy, Incidence (positive or negative) of phosphorylated alpha synuclein deposits. Indicating direct histopathological confirmation of underlying alpha-synuclein degeneration in 5-HT RBD in a cohort of people with 5-HT RBD and matched controls (taking SSRIs but without RBD)., time point 1 (baseline) and time point 2 (24 months, +/- 3 months)|Neuromelanin signal intensity in the Subcoeruleus/Coeruleus Complex, Examination of the pontine region of the coeruleus/subcoeruleus complex for evidence of neurodegeneration as well as segment and parcellate REM sleep related neuronal structures., time point 1 (baseline) and time point 2 (24 months, +/- 3 months)|Monopitch as measured by fundamental frequency variability., Participants' voice and speech quality will be examined for synucleinopathy syndrome. The focus on speech function is designed to detect subtle brainstem deficits prior to more overt manifestations of cortical dementia., time point 1 (baseline) and time point 2 (24 months, +/- 3 months)
Secondary Outcome Measures: Subject-specific masks of all REM sleep-related pontine nuclei of interest, volume of Subcoeruleus/Coeruleus Complex., Subject-specific masks of all REM sleep-related pontine nuclei of interest, volume of Subcoeruleus/Coeruleus Complex., time point 1 (baseline) and time point 2 (24 months, +/- 3 months)|Speed of articulatory change as measured by F2 Transitions, Speed of articulatory change as measured by F2 Transitions, which are shown to be reduced in people with dysarthria, time point 1 (baseline) and time point 2 (24 months, +/- 3 months)