Neuroplasticity in RBD

Neuroplasticity in REM Sleep Behavior Disorder

REM sleep behavior disorder is a parasomnia that reflects the presence of alpha-synucleinopathy in the brain and is highly predictive of eventual phenoconversion to Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy over the course of years to decades. Neuroplastic adaptations in the brain during the prodromal stage of disease are thought to mask the expression of motor and non-motor signs and may substantially delay diagnosis during a potentially critical time window. This study will examine the state and progression (over 30 to 36 months) of neuroplastic changes in the excitability of the motor and prefrontal cortex (using transcranial magnetic stimulation), the structural and functional connectivity of the brain (using highfield, 7T, magnetic resonance imaging), and the relationship of these changes to the expression of motor and neuropsychological signs, in a cohort of individuals with REM sleep behavior disorder and matched controls.

Study Overview

• Status: Recruiting
• Conditions: REM Sleep Behavior Disorder
• Intervention / Treatment: Other: Natural progression over time

• Study Type: Interventional
• Enrollment (Estimated): 86
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Madison Wylie, MS; Phone Number: 612-505-8325; Email: aasen056@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota
      • Principal Investigator: Colum MacKinnon, PhD
      • Contact: Madison Wylie, MS; Phone Number: 612-505-8325; Email: aasen056@umn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Study Population

A total of 62 people with iRBD and 24 healthy age- and sex-matched control subjects will be recruited and enrolled for this project with the goal to complete testing in a least 50 iRBD and 16 control subjects at the 30-36 month follow-up time point (conservatively assuming a maximum 20% dropout rate).

Description

Inclusion Criteria for the iRBD Group:

• Diagnosis of polysomnogram-confirmed isolated iRBD.
• Able to ambulate independently without the use of an assistive device (e.g., cane) for 50 meters.
• Age: 21-75 years.

Inclusion Criteria For Control Subject Group:

• Age: 21-75 years.
• Able to ambulate independently without the use of an assistive device (e.g., cane or walker for 50 meters.

Exclusion criteria for iRBD group:

• Dementia diagnosis and/or a University of California Brief Assessment of Capacity to Consent (UBACC) score and MacCAT-CR score indicating impaired capacity to consent.
• History of musculoskeletal disorders that significant affect movement of lower or upper limbs as determined at the time of enrollment.
• Other significant neurological disorders that may affect participation or performance in the study.
• Anti-depressant associated RBD. Individuals will be excluded if their dream enactment emerged or clearly worsened after initiating an antidepressant medication.
• Meet criteria for overt Parkinson's disease, dementia with Lewy bodies, Multiple Systems Atrophy, Alzheimer's disease, or other neurodegenerative disorder, or other known cause of RBD (e.g., narcolepsy and drug induced RBD).
• Untreated sleep-disordered breathing
• History of musculoskeletal disorders that significantly affect movement of lower or upper limbs as determined at the time of enrollment.
• Pregnant women

• Additional exclusion criteria for TMS experiments (note that individuals who are excluded from the TMS experiment still have the opportunity to participate in the other data collection sessions):

  • History of seizures, epilepsy, stroke, multiple sclerosis, or traumatic brain injury
  • Recent history of frequent syncope (fainting) episodes in response to blood, emotional stress, or sensory triggers.
  • Intracranial metallic or magnetic devices (e.g. cochlear implant, deep brain stimulator)
  • Pacemaker or any implanted device
  • History of surgery on blood vessels, brain, or heart
  • Unexplained, recurring headaches or concussion within the last six months
  • Severe hearing impairment
  • If participant is taking one of the following medications that affects neuroplasticity testing, they will be excluded from the TMS experiment: haloperidol (dopamine antagonist), prazosin (norepinephrine antagonist), biperiden (acetylcholine antagonist), dopamine modulators, NMDA receptor and calcium channel modulators, GABAergic drugs (benzodiazepines), lithium, lovastatin, and cannabis.

Exclusion Criteria for Control subject Group:

• Same as exclusion criteria as the iRBD group
• History of dream enactment from either patient report or from a bed partner witness that may suggest iRBD.
• History of untreated sleep-disordered breathing.
• Presence of parkinsonism or cognitive impairment (including dementia or mild cognitive impairment).
• Active central nervous system, systemic, psychiatric conditions or use of psychoactive medication that would adversely affect cognitive, neuropsychiatric, motor, or autonomic functioning

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: iRBD Group: Progression over time; Each subject be assessed at baseline and approximately 2 years later. At each time point, each participant will attend eight testing sessions (MRI scanning, two TMS-motor test visits, two TMS-prefrontal test visits, motor assessments, neuropsychological testing, and overnight sleep testing (polysomnography - PSG).	Other: Natural progression over time; Each subject will attend eight testing sessions (MRI scanning, two TMS-motor test visits, two TMS-prefrontal test visits, motor assessments, neuropsychological testing, and overnight sleep testing (polysomnography - PSG).
Other: Control Group: Progression over time; Each subject be assessed at baseline and approximately 2 years later. At each time point, each participant will attend eight testing sessions (MRI scanning, two TMS-motor test visits, two TMS-prefrontal test visits, motor assessments, neuropsychological testing, and overnight sleep testing (polysomnography - PSG).	Other: Natural progression over time; Each subject will attend eight testing sessions (MRI scanning, two TMS-motor test visits, two TMS-prefrontal test visits, motor assessments, neuropsychological testing, and overnight sleep testing (polysomnography - PSG).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI Progression over 30 to 36 months	Yes/No whether a change was observed from baseline	30 to 36 months from baseline
Change in Beck Depression Inventory score	Higher score means more impairment	30 to 36 months from baseline
Change in Mattis Dementia Rating Scale	Higher score means less impairment	30 to 36 months from baseline
Change in Rey Complex Figure	Higher score means less impairment	30 to 36 months from baseline
Change in WAIS-IV Matrix Reasoning	Higher score means less impairment	30 to 36 months from baseline
Change in Stroop Color	Higher score means less impairment	30 to 36 months from baseline
Change in Stroop Word	Higher score means less impairment	30 to 36 months from baseline
Change in Stroop Color Word	Higher score means less impairment	30 to 36 months from baseline
Change in Wisconsin Card Sorting Test	Higher score means more impairment for subsections "# persev errors" and FMS; less impairment for subsections "# categories" and conceptualization	30 to 36 months from baseline
Change in D-KEFS	Higher score means less impairment	30 to 36 months from baseline
Change in BVMT-R	Higher score means less impairment	30 to 36 months from baseline
Change in HVLT	Higher score means less impairment	30 to 36 months from baseline
Change in WMS-3 Spatial Span	Higher score means less impairment	30 to 36 months from baseline
Change in Boston Naming Test	Higher score means less impairment	30 to 36 months from baseline
Change in Trail Making Test A	Higher score means more impairment	30 to 36 months from baseline
Change in Trail Making Test B	Higher score means more impairment	30 to 36 months from baseline

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Colum MacKinnon, Ph.D, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2023
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: July 20, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (Actual): July 25, 2022

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: iRBD
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Parasomnias; REM Sleep Parasomnias; REM Sleep Behavior Disorder
• Other Study ID Numbers: NEUR-2022-30985

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No