Prospective Neuroimaging Investigation of Idiopathic REM Sleep Behavior Disorder

A Prospective Longitudinal Neuroimaging and Biomarker Cohort Study in Idiopathic Rapid Eye Movement(REM) Sleep Behavior Disorder

This is a prospective cohort study to evaluate degenerative changes in the brain by performing functional imaging analysis in patients with RBD and its correlations with clinical symptoms and dopaminergic degeneration. This study also evaluates cognitive changes with functional imaging measures and olfactory and other premotor symptoms of Lewy body disease. This study also collects gene extracts and sera to develop a biomarker for early detection of neurodegeneration.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease; REM Sleep Behavior Disorder
• Intervention / Treatment: Other: testing, evaluation, sampling

Detailed Description

This study will include 3 groups in relation with RBD: idiopathic RBD (iRBD), PD- RBD, normal controls without RBD. In all groups, neurological examinations, olfactory testings, nonmotor symptoms evaluations, neuropsychological evaluations (detailed outcomes are in the outcome section) will be performed at baseline evaluation after enrollment. Image data will be obtained on following modalities: brain magnetic resonance imaging (MRI), 18F-N-ω-fluoropropyl- 2β-carbomethoxy- 3β-(4-iodophenyl) nortropane ([18F]FP-CIT) positron emission tomography (PET), and 18F-fludeoxyglucose([18F]FDG) PET.

To assess progression toward Lewy body disorders, patients in iRBD group will be evaluated at 2, and 4 years of follow-up visit. Clinical, neuropsychological tests, brain MRI, and two PET scans will be administered. After 4 years, patients who are willing to participate will be additionally followed-up yearly as a routine clinical visit with clinical and neurological examinations until obvious signs of Lewy body diseases will develop.

In PD-RBD group, patients will be evaluated at 3-year follow-up period amongst days of routine clinic visits with administering clinical and neuropsychological tests.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • SMG-SNU Boramae Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

iRBD group:

• A diagnosis of RBD according to the international classification of sleep disorders-2 (ICSD-2) criteria
• No current neurological diseases related with RBD
• Male or female aged from 30 to 80 years old at screening
• Subject enrolled voluntarily and understood the contents of the study

PD group:

• A diagnosis of PD according to the UK Brain Bank Diagnostic Criteria
• A diagnosis of RBD according to the international classification of sleep disorders-2 (ICSD-2) criteria
• Male or female aged from 30 to 80 years old at screening
• Subject enrolled voluntarily and understood the contents of the study

Control group:

• No current neurological or psychiatric diseases related with RBD
• Male or female aged from 30 to 80 years old at screening
• Age and sex matched with those of subjects in iRBD group
• Subject enrolled voluntarily and understood the contents of the study

Exclusion Criteria:

• Clinically significant cognitive decline unable to follow the study (Mini-mental state examination [MMSE] score less than 20)
• History of psychiatric illnesses (ex. depression)
• Unable to walk and cooperate to the examination
• Unable to take magnetic resonance imaging or positron emission tomography
• Existence of illness or problems which makes difficult to be enrolled to the study judged by clinicians

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: idiopathic RBD group; A group of patients diagnosed as idiopathic RBD that is confirmed by polysomnography. Interventions as testing, evaluation, samplings at baseline, then repeat at 2 years and 4 years of prospective follow-up. thereafter only clinical observations until Lewy body disease is diagnosed.	Other: testing, evaluation, sampling; neuroimaging biomarkers using positron emission tomography and magnetic resonance imaging, and evaluation of neurological & neurocognitive status by using a predefined neuropsychological assessment battery.
Active Comparator: incident PD group; A group of patients who are newly diagnosed as Parkinson's disease, and never been treated with prolonged history of probable RBD. Interventions as testing, evaluation, sampling at baseline and then evaluations only at 3 year follow-up after anti-parkinsonian treatment.	Other: testing, evaluation, sampling; neuroimaging biomarkers using positron emission tomography and magnetic resonance imaging, and evaluation of neurological & neurocognitive status by using a predefined neuropsychological assessment battery.
Placebo Comparator: Control; Control group includes elderly controls without neurodegerative diseases examined by neurologists. Interventions as testing, evaluation, sampling at baseline only.	Other: testing, evaluation, sampling; neuroimaging biomarkers using positron emission tomography and magnetic resonance imaging, and evaluation of neurological & neurocognitive status by using a predefined neuropsychological assessment battery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of development of Lewy body diseases	idiopathic RBD group only	up to 4-years follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parkinsonian motor symptoms score change measured by the unified Parkinson's disease rating scale (MDS-UPDRS)	descriptive, intragroup analysis	from baseline to 2-years and 4-years follow-up (iRBD group), to 3-years follow-up (PD-RBD group)
Nonmotor symptoms profile change assessed by a combined evaluatin using the non-motor symptom scale and part I of the MDS-UPDRS	descriptive, intragroup analysis	from baseline to 2-years and 4-years follow-up (iRBD group), to 3-years follow-up (PD-RBD group)
Cognitive change measured by the neuropsychological test battery	descriptive, intragroup analysis	from baseline to 2-years ad 4-years follow-up (iRBD group), to 3-years follow-up (PD-RBD group)
Degenerative brain changes predicted by MRI (diffusion tensor analysis and volumetry)	descriptive, intragroup analysis	from baseline to 2-years and 4-years follow-up (iRBD group only)
Functional network changes predicted by the resting-state functional MRI	descriptive, intragroup analysis	from baseline to 2-years and 4-years follow-up (iRBD group only)
Degenerative brain changes predicted by [18F]FP-CIT PET	descriptive, intragroup analysis	from baseline to 2-years and 4-years follow-up (iRBD group only)
Functional network changes predicted by [18F]FDG PET	descriptive, intragroup analysis	from baseline to 2-years and 4-years follow-up (iRBD group only)

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: SMG-SNU Boramae Medical Center
• Investigators: Principal Investigator: Jee-Young Lee, MD, PhD, SMG-SNU Boramae Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2013
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: November 30, 2016
• First Submitted That Met QC Criteria: December 5, 2016
• First Posted (Estimate): December 6, 2016

Study Record Updates

• Last Update Posted (Actual): March 18, 2020
• Last Update Submitted That Met QC Criteria: March 17, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Imaging; Parkinson disease; Bio-markers; Lewy body disease; Prospective cohort; REM Sleep Behavior Disorder
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sleep Wake Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parasomnias; REM Sleep Parasomnias; Disease; Parkinson Disease; Mental Disorders; REM Sleep Behavior Disorder
• Other Study ID Numbers: 16-2013-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED