Striatal Dopamine Transmission in Individuals With Isolated Rapid Eye Movement Sleep With Atonia: a Search for Precursor Biomarker for Neurodegeneration

February 23, 2021 updated by: Professor Wing Yun Kwok, Chinese University of Hong Kong

Background:

Previous studies have confirmed that most patients with idiopathic REM sleep behaviour disorder (iRBD) eventually develop neurodegenerative diseases. In addition, REM sleep without atonia (RSWA), a hallmark of RBD feature, is a significant predictor of development of neurodegenerative diseases in patients with iRBD. Some preliminary studies have implied that isolated RSWA in the absence of RBD symptoms may also indicate neurodegeneration. However, this speculation needs to be confirmed by more refined study with sophisticated measures in both RSWA and markers of neurodegeneration

Objectives: 1) to determine the differences in striatal dopamine transmission and other markers of neurodegeneration among individuals with isolated RSWA and healthy controls; 2) to examine the correlation of severity of RSWA with striatal dopamine transmission.

Design: Case-control study

Setting: Community-based sample

Participants: 1) iRBD first degree relatives with isolated RSWA (n=18) 2) iRBD first degree relatives without isolated RSWA (n=18) 3) Community-based health controls without isolated RSWA (n=18)

Main outcome measures:

  1. The dopamine transmission as measured by triple-tracer PET/ CT imaging protocol including 18F-DOPA, 11C-Raclopride and 18F-FDG images;
  2. Brain glucose metabolism and neurocognitive measures;
  3. Severity of EMG activity during REM sleep

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

In the past two decades, a number of studies have confirmed that most patients with idiopathic RBD will eventually develop neurodegenerative diseases, especially α-synucleinopathies. Previous studies, including our preliminary data, suggested that RSWA is a marker of predicting the conversion of neurodegenerative diseases in idiopathic RBD. In other words, RSWA is an early marker of neurodegeneration in patients with idiopathic RBD. However, a number of individuals who are absent of any RBD symptoms (including patients with α-synucleinopathies, also have RSWA, which is described to have isolated RSWA. Only a few studies have attempted to understand the clinical importance and predictive prognosis of isolated RSWA. These preliminary studies suggest that isolated RSWA in healthy subjects may be a silent biomarker of neurodegeneration. However, these preliminary findings need to be replicated and confirmed by more refined study with dopamine neurotransmission neuroimaging.

This proposed study will enrich the limited scientific literature of the potential pathogenesis and progression of isolated RSWA. By using an ongoing family study, we have screened a number of individuals with isolated RSWA, who are the first degree relatives of patients with RBD and are presumed to have a higher risk of neurodegeneration. Based on the existing sample, the current study will provide the first neuroimaging data on isolated RSWA to test the hypothesis that isolated RSWA, even in the absence of RBD symptoms, is an early marker of neurodegeneration. Individuals with isolated RSWA are expected to show dopamine dysfunction when compared with individuals without RSWA. If we confirm this hypothesis, the findings in the current study will extend our understanding of the spectrum of RBD and RSWA. The potential implication of our findings is that asymptomatic RSWA, especially in the presence of family history, will harbour the neurodegenerative progression. The results will pave the way for future prospective follow up to determine the course of neurodegeneration. From an etiological understanding, it will help to expand the understanding of the evolution course of synucleinopathy neurodegeneration. From an interventional angle, this study will have significant implication for developing a longer prevention window for neuroprotective trial.

The inclusion criteria for the subjects:

iRBD first degree relatives with isolated RSWA

  1. First degree relatives of patients with iRBD;
  2. Age 45 years or above;
  3. Absence of dream enactment behaviors;
  4. A total score on REM Sleep Behavior Questionnaire (RBDQ-HK) less than 19, which is the cut-off suggestive of a diagnosis of RBD;
  5. Presence of RSWA as measured by v-PSG; RSWA is defined as the percentage of increased EMG activity (phasic or tonic) at least 10% during REM sleep for any channel.
  6. for those individuals with moderate to severe obstructive sleep apnea (apnea-hypopnea index, AHI > 15/hour), effective CPAP treatment should be documented and a second night of V-PSG is required to determine RSWA.

Community-based health controls without isolated RSWA:

  1. No family history of RBD;
  2. Age- and sex- matched with isolated RSWA subjects
  3. Absence of dream enactment behaviors;
  4. A score of RBDQ-HK less than 19;
  5. Absence of RSWA as measured by v-PSG;
  6. for those individuals with moderate obstructive sleep apnea (AHI > 15/hour), effective CPAP treatment should be documented and a second night of V-PSG is required to determine RSWA.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
      • Shatin, Hong Kong
        • Shatin Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

41 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Subjects will be identified and recruited from our previous cohort.

Description

Inclusion Criteria:

  1. No family history of RBD;
  2. Age- and sex- matched with isolated RSWA subjects
  3. Absence of dream enactment behaviors;
  4. A score of RBDQ-HK less than 19;
  5. Absence of RSWA as measured by v-PSG;
  6. for those individuals with moderate obstructive sleep apnea (AHI > 15/hour), effective CPAP treatment should be documented and a second night of V-PSG is required to determine RSWA.

Exclusion Criteria:

  1. Presence of dream enactment behaviors by self-report or documented by v-PSG;
  2. Presence of narcolepsy and other neurological diseases that may give rise to RBD and RWSA;
  3. Presence of neurodegenerative diseases;
  4. A total score of the MOCA ≤ 22 and the CDR ≥ 1.
  5. On medication that potentially increases EMG activity and triggers the symptoms of RBD, such as antidepressants;
  6. On medication that affects dopamine neural transmission;
  7. Not capable of giving informed consent for participation of the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
health Control
  1. No family history of RBD;
  2. Age- and sex- matched with isolated RSWA subjects
  3. Absence of dream enactment behaviors;
  4. A score of RBDQ-HK less than 19;
  5. Absence of RSWA as measured by v-PSG;
  6. for those individuals with moderate obstructive sleep apnea (AHI > 15/hour), effective CPAP treatment should be documented and a second night of V-PSG is required to determine RSWA.
Case with isolated RSWA
  1. First degree relatives of patients with iRBD;
  2. Age 45 years or above;
  3. Absence of dream enactment behaviors;
  4. A total score on REM Sleep Behavior Questionnaire (RBDQ-HK) less than 19, which is the cut-off suggestive of a diagnosis of RBD;
  5. Presence of RSWA as measured by v-PSG; RSWA is defined as the percentage of increased EMG activity (phasic or tonic) at least 10% during REM sleep for any channel.
  6. for those individuals with moderate to severe obstructive sleep apnea (apnea-hypopnea index, AHI > 15/hour), effective CPAP treatment should be documented and a second night of V-PSG is required to determine RSWA.
Case without isolated RSWA
  1. First degree relatives of patients with iRBD;
  2. Age- and sex- matched with isolated RSWA subjects;
  3. Absence of dream enactment behaviors;
  4. A score of RBDQ-HK less than 19;
  5. Absence of RSWA as measured by v-PSG;
  6. for those individuals with moderate obstructive sleep apnea (AHI > 15/hour), effective CPAP treatment should be documented and a second night of V-PSG is required to determine RSWA.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dopamine neurotransmission
Time Frame: 24 months
PET dopamine neurotransmission with a specific interest in striatal dopamine transmission
24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
REMREEA
Time Frame: 24 months
Correlations of severity of REMREEA with dopamine transmission, brain glucose metabolism, and neurocognitive measures.
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Chinese University of Hong Kong

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Yun Kwok Wing, Professor, Chinese University of Hong Kong

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 30, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 8, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 21, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 21, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 27, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 24, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 23, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HMRF04153036

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

In this stage, we didin't decide which information of IPD will share with other researchers

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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