Prodromal Markers of First-degree Relatives of Patients With Psychiatric Disorders Comorbid With RBD

NCT03595475 | Completed

• 1 other identifier: RGC14172917
• Study Type: observational
• Target: 408
• Locations: 1 country
• Sites: 2

Brief Summary

REM sleep behavior disorder (typical or 'idiopathic' RBD, iRBD) is a novel and distinct parasomnia characterized by recurrent dream enactment behaviours and polysomnographic features of loss of normal REM-sleep related muscle atonia, with a male predominance commonly occurring at the age of 60's. A majority of the patients with iRBD will eventually develop α-synucleinopathy (e.g., Parkinson's disease). On the other hand, growing evidence reveals a specific group of psychiatric patients demonstrating comparable clinical RBD features (pRBD) (e.g., abnormal REM-related electromyographic (EMG) activities) as found in typical iRBD, but with less male predominance occurring at the age of mid 40's to early 50's. Although recent findings from both cross-sectional and prospective studies have suggested that pRBD is likely to be a persistent parasomnia with close association with clinical and neuroimaging biomarkers related to neurodegeneration, the nosology of the development of RBD symptoms among patients with psychiatric disorders, notably major depressive disorder, remains unclear as to whether they are simply antidepressants related, or represent a part of the early phase of α-synucleinopathy neurodegeneration. Family studies on iRBD have confirmed a significant familial aggregation of iRBD with a higher rate of RBD cases and presence of prodromal neurodegenerative biomarkers (e.g. tonic EMG activity during REM sleep, constipation, and motor function impairments) of α-synucleinopathy neurodegeneration among first-degree relatives (FDRs) of patients with iRBD. Thus, the investigators propose this family study to examine the following hypotheses: 1) FDRs of patients with pRBD have a higher rate of RBD symptoms and its core features when compared to FDRs of controls with and without psychiatric disorders; 2) FDRs of pRBD are more likely to exhibit the features associated with prodromal markers of α-synucleinopathy neurodegeneration when compared with FDRs of controls with and without psychiatric disorders; 3) FDRs of patients with pRBD have a higher rate of α-synucleinopathy neurodegeneration when compared with FDRs of controls with and without psychiatric disorders. A total of 176 FDRs from each group (e.g., pRBD cases, psychiatric controls, and healthy controls) will be recruited to undergo a face-to-face clinical interview and a series of assessments on prodromal markers of Parkinson's diseases (as according to the International Parkinson and Movement Disorder Society research criteria) respectively. All FDRs with possible RBD and a subset of FDRs without possible RBD will be invited to undergo one-night video-polysomnographic assessment to confirm the clinical diagnosis of RBD and to assess the abnormal REM-related EMG muscle activities.

Conditions

REM Sleep Behavior Disorder

Keywords

Prodromal markers; Psychiatric disorders; α-synucleinopathy; Family study

Outcome Measures

Primary Outcomes (1)

• Prevalence of possible REM Sleep Behavior Disorder

  The prevalence of possible REM Sleep Behavior Disorder based on the self-reported/proxy-reported REM Sleep Behavior Disorder symptoms in REM Sleep Behavior Disorder Questionnaire-HK among First Degree Relatives,

  17 months

Secondary Outcomes (3)

• Percentage of REM-related EMG activity

  17 months

• Weighted prevalence of Polysomnography confirmed REM Sleep Behavior Disorder

  17 months

• Recurrence risk of Parkinson's disease

  17 months

Study Arms (3)

Psychiatric RBD cases

1. Presence of REM sleep without atonia; 2. At least one of the followings is present: i). Dream enactment behaviors, SRIs, potentially injurious or disruptive behaviors by history; ii). Abnormal REM sleep behaviors documented during v-PSG monitoring; 3. Absence of electroencephalogram (EEG) epileptiform activity during REM sleep unless RBD can be clearly distinguished from any concurrent REM sleep related seizure disorder; 4. The sleep disturbance is not better explained by other sleep disorder (e.g., obstructive sleep apnea, medical or neurological disorder, mental disorder, medication use, or substance use disorder)

Psychiatric control

1. Age- and sex- matched with pRBD proband; 2. Concurrent psychiatric illnesses according to the Mini International Neuropsychiatric Interview( M.I.N.I); 3. Free of narcolepsy and other neurological diseases; 4. Absence of any RBD features as based on REM sleep behavior disorder questionnaire (RBDQ-HK) and v-PSG; 5) Free of neurodegenerative diseases

Healthy control

1. Age- and sex- matched with pRBD proband; 2. Without lifetime psychiatric disorder according to Mini International Neuropsychiatric Interview( M.I.N.I); 3. Free of narcolepsy and other neurological diseases; 4. Absence of any RBD features as based on RBDQ-HK and v-PSG; 5. Free of neurodegenerative diseases

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

In this study, we will employ a combination of family history (proxy report for unavailable/inaccessible subjects) and study (face-to face interview, clinical and sleep study) method in determining the familial aggregation of pRBD. The flowchart of subject recruitments is presented in Figure 1. The study subjects are the FDRs of pRBD cases, psychiatric controls and healthy controls. As previous studies have suggested that depression is a significant risk factor of development of Parkinson's Disease, we will include two control groups. First, those FDRs of patients with psychiatric disorders in addition to the FDRs of healthy controls (free of depression and RBD), in consideration of the potential associations of proband's psychiatric disorders with prodromal markers of Parkinson's Disease in the FDRs.

You may qualify if:

• Age- and sex- matched with pRBD proband;
• Without lifetime psychiatric disorder according to Structural Clinical Interview for DSM-IV Disorders (SCID);
• Free of narcolepsy and other neurological diseases;
• Absence of any RBD features as based on RBDQ-HK and v-PSG;
• free of neurodegenerative diseases.

You may not qualify if:

• Not Chinese or aged under 40 years old;
• Refuse to participate in this study;
• without a biological relationship with proband.

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (2)

The Chinese University of Hong Kong

Hong Kong, Hong Kong

Location

Shatin Hospital

Shatin, Hong Kong

Location

Related Publications (1)

• Wang J, Lam SP, Huang B, Liu Y, Zhang J, Yu MWM, Tsang JCC, Zhou L, Chau SWH, Chan NY, Chan JWY, Schenck CH, Li SX, Mok VCT, Ma KKY, Chan AYY, Wing YK. Familial alpha-synucleinopathy spectrum features in patients with psychiatric REM sleep behaviour disorder. J Neurol Neurosurg Psychiatry. 2023 Nov;94(11):893-903. doi: 10.1136/jnnp-2022-330922. Epub 2023 Jun 30.

  PMID: 37399287 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood sample will be taken for genetic study.

MeSH Terms

Conditions

REM Sleep Behavior Disorder; Mental Disorders

Condition Hierarchy (Ancestors)

REM Sleep Parasomnias; Parasomnias; Sleep Wake Disorders; Nervous System Diseases

Study Officials

• Yun Kwok Wing, Professor

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 12, 2018
• First Posted: July 23, 2018
• Study Start: October 1, 2017
• Primary Completion: November 30, 2021
• Study Completion: March 31, 2022
• Last Updated: October 28, 2022

Record last verified: 2022-10

Locations

HK (2)