Identification of Prodromal Neurodegeneration in Serotonergic-Induced REM Sleep Behavior Disorder
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Skin biopsy, Speech testing, Ultra high field 7T MRI.
- Who it may be relevant to
- Registry conditions: Dementia With Lewy Bodies, Parkinson Disease, REM Sleep Behavior Disorder. Basic parameters: 18 years — 75 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
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.
Interventions
- Diagnostic test Skin biopsy
Skin biopsy to detect systemic alpha-synuclein pathology in 5-HT RBD - Diagnostic test Speech testing
Speech Testing to quantify evolving signs of 5-HT RBD - Diagnostic test Ultra high field 7T MRI
7T MRI to examine 5-HT RBD for evidence of brainstem neurodegeneration
Primary outcome measures
- Phosphorylated alpha synuclein deposits on skin biopsy [Time frame: time point 1 (baseline) and time point 2 (24 months, +/- 3 months)]
- Neuromelanin signal intensity in the Subcoeruleus/Coeruleus Complex [Time frame: time point 1 (baseline) and time point 2 (24 months, +/- 3 months)]
- Monopitch as measured by fundamental frequency variability. [Time frame: time point 1 (baseline) and time point 2 (24 months, +/- 3 months)]
Secondary outcome measures (2)
- 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)]
- Speed of articulatory change as measured by F2 Transitions [Time frame: time point 1 (baseline) and time point 2 (24 months, +/- 3 months)]
Eligibility criteria
Inclusion criteria
Serotonergic REM sleep behavior (5-HT RBD) participants
Inclusion criteria
- 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
Inclusion criteria
- 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.
The following serotonergic medications will be included:
Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, and Sertraline
Exclusion criteria
Serotonergic REM sleep behavior (5-HT RBD) participants
Exclusion criteria
- 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
- History of dysarthria, aphasia or other condition which could interfere with speech assessment
- Reduced capacity to consent
- MRI exclusion criteria for 7T scans: presence of any metallic clip(s) or implantable medical devices (e.g., heart valve, aneurysm clip, coils or surgery, renal or aortic clips, shunts, stents or stent grafts, metal mesh/coil implants, neurostimulator, insulin pump, IVC filter, etc.).
- History of allergic response to xylocaine or other local anesthesia
- Pregnant women will be excluded due to unknown risk of MRI on developing fetus Control Participants
Exclusion Criteria: same exclusion criteria as 5-HT RBD group, plus the following:
- History of dream enactment that may suggest RBD
- Increased REM motor tone (REM atonia index > 0.10) on PSG suggestive of RBD
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Basic science
Study locations
United States · 1 center
- University of Minnesota — Minneapolis
Identifiers
NCT: NCT06467461 · NEUR-2023-32484