Identification of Prodromal Neurodegeneration in Serotonergic-Induced REM Sleep Behavior Disorder
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-75
SponsorUniversity of Minnesota
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Diagnosis of polysomnogram-confirmed RBD with history of dream enactment or clear dream enactment visualized on video from polysomnogram.
History of dream enactment began shortly after (less than 2 months) starting a serotonergic antidepressant medication. Control Participants
Age (±3 years) and sex matched to participants with 5-HT RBD
On serotonergic medication for at least 6 months without history of dream enactment.
Disqualifiers
Younger than 18
Older than 75
Meet criteria for Parkinson's disease, dementia with Lewy bodies, Multiple System Atrophy, Pure Autonomic Failure, Alzheimer's disease, other diagnosed neurodegenerative disorder, or other known cause of RBD (e.g. narcolepsy)
Untreated obstructive sleep apnea, obesity hypoventilation, central sleep apnea or other sleep disordered breathing
Trial design
Design model
Single group
Treatments tested in this trial
Skin biopsy
Diagnostic testSkin biopsy to detect systemic alpha-synuclein pathology in 5-HT RBD
Speech testing
Diagnostic testSpeech Testing to quantify evolving signs of 5-HT RBD
Ultra high field 7T MRI
Diagnostic test7T MRI to examine 5-HT RBD for evidence of brainstem neurodegeneration
Treatment groups
60 Participants
are divided into 1 treatment groupGroup A: Research participantsOther 3 interventions
Trial outcomes
Primary outcomes
1
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 frame
time point 1 (baseline) and time point 2 (24 months, +/- 3 months)2
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 frame
time point 1 (baseline) and time point 2 (24 months, +/- 3 months)3
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 frame
time point 1 (baseline) and time point 2 (24 months, +/- 3 months)Secondary outcomes
1
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 frame
time point 1 (baseline) and time point 2 (24 months, +/- 3 months)2
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 frame
time point 1 (baseline) and time point 2 (24 months, +/- 3 months)Sponsors and contacts
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Source ClinicalTrials.gov