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NCT Number: NCT06467461

Identification of Prodromal Neurodegeneration in Serotonergic-Induced REM Sleep Behavior Disorder

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.

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Key information

Conditions

Dementia With Lewy Bodies Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Dementia Lewy Body Disease Mental Disorders Movement Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Parasomnias Parkinson Disease Parkinsonian Disorders REM Sleep Behavior Disorder REM Sleep Parasomnias Sleep Wake Disorders Synucleinopathies

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location status: Recruiting

Location contact

Joy Schmidt

CONTACT

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Skin Biopsy

Diagnostic Test

Skin biopsy to detect systemic alpha-synuclein pathology in 5-HT RBD

Speech testing

Diagnostic Test

Speech Testing to quantify evolving signs of 5-HT RBD

Ultra high field 7T MRI

Diagnostic Test

7T MRI to examine 5-HT RBD for evidence of brainstem neurodegeneration

Primary outcomes

  1. Phosphorylated alpha synuclein deposits on skin biopsy

    Time frame: time point 1 (baseline) and time point 2 (24 months, +/- 3 months)

    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).

  2. Neuromelanin signal intensity in the Subcoeruleus/Coeruleus Complex

    Time frame: time point 1 (baseline) and time point 2 (24 months, +/- 3 months)

    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.

  3. Monopitch as measured by fundamental frequency variability.

    Time frame: time point 1 (baseline) and time point 2 (24 months, +/- 3 months)

    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.

Secondary outcomes

  1. 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)

    Subject-specific masks of all REM sleep-related pontine nuclei of interest, volume of Subcoeruleus/Coeruleus Complex.

  2. Speed of articulatory change as measured by F2 Transitions

    Time frame: time point 1 (baseline) and time point 2 (24 months, +/- 3 months)

    Speed of articulatory change as measured by F2 Transitions, which are shown to be reduced in people with dysarthria

Study contacts

Contact information is provided by the study sponsor or research team.

Joy Schmidt

CONTACT

[email protected]

(612) 624 -1456

Sponsors and collaborators

Lead sponsor

University of Minnesota

Other

Registry information

Important dates

Study start
2024
Primary completion
2027
Study completion
2028
First posted
Jun 21, 2024
Registry last updated
Jul 8, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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