Prospective Neuroimaging Investigation of Idiopathic REM Sleep Behavior Disorder

Sponsor

Seoul National University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02984137

Collaborator

SMG-SNU Boramae Medical Center (Other)

Enrollment

Location

Arms

Actual Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease REM Sleep Behavior Disorder	Other: testing, evaluation, sampling	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Diagnostic

Official Title:

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

Actual Study Start Date :

Jun 1, 2013

Actual Primary Completion Date :

Aug 1, 2018

Actual Study Completion Date :

Aug 1, 2018

Arms and Interventions

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.

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

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

Outcome Measures

Primary Outcome Measures

Frequency of development of Lewy body diseases [up to 4-years follow-up]
idiopathic RBD group only

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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