Neuroplasticity in RBD

Parkinson Clinical Trial

Official title:

Neuroplasticity in REM Sleep Behavior Disorder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05471960
• Other study ID #: NEUR-2022-30985
• Status: Recruiting
• Start date: August 1, 2022
• Est. completion date: August 1, 2030

Study information

• Verified date: July 2023
• Source: University of Minnesota
• Contact: Josh De Kam
• Phone: 612-626-8052
• Email: jadekam[@]umn.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 86
• Est. completion date: August 1, 2030
• Est. primary completion date: August 1, 2030
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 75 Years

Eligibility

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
• 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

Related Conditions & MeSH terms

• Parkinson
• Parkinson Disease

Intervention

Other:
• No intervention
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).

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	MRI Progression over 30 to 36 months	Yes/No whether a change was observed from baseline	30 to 36 months from baseline
Primary	Change in Beck Depression Inventory score	Higher score means more impairment	30 to 36 months from baseline
Primary	Change in Mattis Dementia Rating Scale	Higher score means less impairment	30 to 36 months from baseline
Primary	Change in Rey Complex Figure	Higher score means less impairment	30 to 36 months from baseline
Primary	Change in WAIS-IV Matrix Reasoning	Higher score means less impairment	30 to 36 months from baseline
Primary	Change in Stroop Color	Higher score means less impairment	30 to 36 months from baseline
Primary	Change in Stroop Word	Higher score means less impairment	30 to 36 months from baseline
Primary	Change in Stroop Color Word	Higher score means less impairment	30 to 36 months from baseline
Primary	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
Primary	Change in D-KEFS	Higher score means less impairment	30 to 36 months from baseline
Primary	Change in BVMT-R	Higher score means less impairment	30 to 36 months from baseline
Primary	Change in HVLT	Higher score means less impairment	30 to 36 months from baseline
Primary	Change in WMS-3 Spatial Span	Higher score means less impairment	30 to 36 months from baseline
Primary	Change in Boston Naming Test	Higher score means less impairment	30 to 36 months from baseline
Primary	Change in Trail Making Test A	Higher score means more impairment	30 to 36 months from baseline
Primary	Change in Trail Making Test B	Higher score means more impairment	30 to 36 months from baseline