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

Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06467461
• Other study ID #: NEUR-2023-32484
• Status: Recruiting
• Start date: February 8, 2024
• Est. completion date: December 30, 2028

Study information

• Verified date: June 2024
• Source: University of Minnesota
• Contact: Joy Schmidt
• Phone: (612) 624 -1456
• Email: schmidtj[@]umn.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 30, 2028
• Est. primary completion date: September 1, 2028
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Dementia With Lewy Bodies
• Lewy Body Disease
• Mental Disorders
• Nerve Degeneration
• Parkinson Disease
• REM Sleep Behavior Disorder

Intervention

Other:
• No intevention
No intervention. This is an observational study

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the incidence (positive or negative) of phosphorylated alpha synuclein deposits	Participating subjects will have three small skin punch biopsies for a targeted skin biopsy using CND Lifesciences Syn-One Test. We are seeking 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).	Baseline (Time 1) and Follow-up after 24 months, +/- 3 months (Time 2)
Primary	neuromelanin signal intensity in the Subcoeruleus/Coeruleus Complex	Participants will have a 7T MRI of the brain 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	Baseline (Time 1) and Follow-up after 24 months, +/- 3 months (Time 2)
Primary	monopitch measured by fundamental frequency variability	In a Computerized Speech Lab, participant's voice and speech quality will be recorded in a quiet room with reduced acoustic reverberation in order to investigate whether individuals with 5-HT RBD have a synucleinopathy syndrome. The focus on speech function is designed to detect subtle brainstem deficits prior to more overt manifestations of cortical dementia.test for speech deficits	Baseline (Time 1) and Follow-up after 24 months, +/- 3 months (Time 2)