Active clinical trials for "REM Sleep Behavior Disorder"

To investigate whether a year of rasagiline may reduce the progression from idiopathic REM sleep behavior disorder (RBD) to Parkinson's disease (PD).

The purpose of the study is to investigate the use of a special radioactive drug called 123I-MIBG and myocardial MIBG scintigraphy. This scan may be able to help determine who may have a certain kind of neurologic disorder called Lewy Body Disease. The overall purpose of this study is to correlate myocardial MIBG scintigraphy findings with clinical diagnosis. Myocardial MIBG scintigraphy imaging will be combined with other clinical, neuropsychological and neuroimaging findings to improve the prediction for underlying Lewy Body Disease.

Prospective, single center study to determine whether the current R2* iron mapping method for measuring nigral iron changes in the brain can be significantly improved by using the Quantitative Susceptibility Mapping (QSM) based iron mapping techniques with the goal of validating QSM for potential use in later clinical trials. Subjects with a diagnosis of Parkinson's Disease, Rapid Eye Movement (REM) Sleep Behavior Disorder, and Normal Volunteers who meet the inclusion and exclusion criteria will be eligible for participation in this study.

By 2030 the number of patients with Parkinson's Disease (PD) would increase by 56% affecting 1 out of 120 people older than 45 years-old. It is known that 10-15 years before the onset motor symptoms such as tremor, rigidity and akinesia, patients often experience a specific sleep trouble called REM sleep behaviour disorder (RBD). Follow-up of those subjects showed there was a conversion rate to PD and related disorders (called synucleinopathies) over 80%. The pathophysiology of RBD is poorly understood. The development of cutting-edge technologies such as 7 Tesla MRI and the optimisation of image processing methods made it possible to non-invasively explore in vivo small brain structures involved in sleep and movement disorders. The investigators hypothesize that brain and brainstem microstructure, composition, sodium homeostasis and connectivity may change in 15 isolated RBD (iRBD) subjects compared with 15 healthy controls and that these changes may be correlated with clinical scores. This study would help fill the gap in early diagnosis of synucleinopathies, by contributing to better targeting patients who could be included in therapeutic trials with a neuroprotective effect. Besides, the exploration of original pathophysiological pathways such as sodium homeostatis could provide the necessary arguments for the development of new target therapeutics.

To evaluate the effectiveness of tablet computer-based cognitive training in patients with idiopathic REM sleep behavior disorder.

REM sleep behavior disorder is a novel and distinct parasomnia characterized by recurrent dream enactment behaviors (DEBs) and polysomnographic features of REM sleep without atonia (RSWA), with typical onset age at early 60's. Idiopathic RBD (iRBD) has been suggested as a most specific precursor of α-synucleinopathy-related neurodegeneration (e.g. Parkinson's disease (PD)). There are increasing reports of positive familial cases in both iRBD and PD. In the past few years, the investigators have established the baseline data of a case-control family cohort of iRBD (208 first-degree relatives (FDR) of patients with iRBD and 204 FDRs of controls). Not only did the investigators confirm the familial aggregation of iRBD with neurodegeneration and iRBD cases, the investigator also found that the FDRs harbored a spectrum of isolated RBD features (including DEBs, REM- sleep behavioral events, and RSWA). Besides, when compared with control-FDRs, iRBD-FDRs patients showed more prodromal markers of neurodegeneration (including possible/probable RBD, excessive daytime sleepiness, constipation, and subthreshold parkinsonism) as suggested by the International Parkinson and Movement Disorder Society (MDS) research criteria. The promising baseline findings paved the way for the current proposed prospective study of this unique family cohort. In addition, around 85 unaffected FDRs from each group has repeated the assessments at a mean follow-up duration of about 4 years (early termination of the study supported by RGC- ECS Ref no. 24117018; reason for early termination - ECS PI applicant left the University at early 2020), the preliminary data indicated a persistent familial aggregation of RBD symptoms, loading of prodromal markers (e.g. possible RBD, subthreshold parkinsonism), and a seemingly faster progression into prodromal RBD among the FDRs of iRBD than that of control. This current proposed study is a prospective study with a mean of 7-year follow-up interval to monitor the progression of α- synucleinopathy neurodegeneration and related markers. With the rolling recruitment, the investigators now have 230 control-FDRs and 250 iRBD-FDRs, from which the investigators expect 200 FDRs of each group may respond to the follow-up study. A series of prodromal markers related to neurodegeneration including clinical and sleep assessment (e.g. autonomic symptoms, motor signs, neurocognitive function, sleepiness, vPSG and one-week actigraphy) that were measured at baseline will be reassessed. Specifically, home PSG with a body-movement monitoring system will be additionally implemented in the proposed study to empower the identification of RBD features, especially during the COVID pandemic period at which hospital accessibility is restricted. In addition, the development of clinical neurodegenerative diseases will be ascertained. This proposed study, by recruiting FDRs of iRBD patients (and controls) with prospective study design, will provide novel and important information on the progression of prodromal makers of α-synucleinopathy neurodegenerative diseases in a high-risk population and facilitate further genetic/omics and future neuroprotective intervention study of the familial iRBD.

This study aims to investigate the neural correlates (structural changes, functional connectivity, and structural connectivity of brain structures in prefrontal cortex and basal ganglia) of impulsivity by measuring structures and the blood-oxygen-level-dependent signal of brain in response to impulsive tasks and task-free using functional Magnetic Resonance Image method among healthy controls, patient with prodromal PD (iRBD), and patients with PD.

REM sleep behavior disorder is a novel and distinct parasomnia characterized by recurrent dream enactment behaviors (DEBs) and REM sleep without atonia (RSWA) during polysomnographic assessment, with a male predominance and typical onset age at early 60's. The majority of patients with idiopathic RBD (iRBD) will eventually develop α-synucleinopathy, for instance Parkinson's disease (PD). Thus, iRBD has been considered as a highly specific precursor of α-synucleinopathy-related neurodegeneration. Recently, increasing studies have found that some participants present with only RSWA or DEBs (but without sufficient RSWA), which does not meet the diagnostic criteria for RBD. It has been suggested that these participants with subclinical features (either DEBs or RSWA) might represent a condition known as prodromal RBD. Several emerging evidence, including our own study, have implied a link between isolated RSWA (RSWA without DEBs) and markers of α-synucleinopathy-related neurodegeneration. However, it is still unclear whether the other condition related to RBD, i.e. recurrent DEBs but without sufficient RSWA, is related to a certain degree of α-synucleinopathy. In this regard, the novel concept of recurrent DEBs but without sufficient RSWA, also termed as prodromal/isolated RBD by some researchers, requires validation by further evidence in terms of clinical feature and neurodegenerative prodromal markers perspectives.

Synucleinopathies are a group of rare diseases associated with worsening neurological deficits and the abnormal accumulation of the protein α-synuclein in the nervous system. Onset is usually in late adulthood at age 50 or older. Usually, synucleinopathies present clinically with slowness of movement, coordination difficulties or mild cognitive impairment. Development of these features indicates that abnormal alpha-synuclein deposits have destroyed key areas of the brain involved in the control of movement or cognition. Patients with synucleinopathies and signs of CNS-deficits are frequently diagnosed with Parkinson disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA). However, accumulation of alpha-synuclein and death of nerve cells can also begin outside the brain in the autonomic nerves. In such cases, syncucleinopathies present first with symptoms of autonomic impairment (unexplained constipation, urinary difficulties, and sexual dysfunction). In rare cases, hypotension on standing (a disorder known as orthostatic hypotension) may be the only clinical finding. This "pre-motor" autonomic stage suggests that the disease process may not yet have spread to the brain. After a variable period of time, but usually within 5-years, most patients with abnormally low blood pressure on standing develop cognitive or motor abnormalities. This stepwise evolution indicates that the disease spreads from the body to the brain. Another indication of this spread is that acting out dreams (i.e., REM sleep behavior disorder, RBD) a problem that occurs when the lower part of the brain is affected, may also be the first noticeable sign of Parkinson disease. The purpose of this study is to document the clinical features and biological markers of patients with synucleinopathies and better understand how these disorders evolve over time. The study will involve following patients diagnosed with a synucleinopathy (PD/DLB and MSA) and those believed to be in the "pre-motor" stage (with isolated autonomic impairment and/or RBD). Through a careful series of follow-up visits to participating Centers, we will focus on finding biological clues that predict which patients will develop motor/cognitive problems and which ones have the resilience to keep the disease at bay preventing spread to the brain. We will also define the natural history of MSA - the most aggressive of the synucleinopathies.

This study will enroll participants with idiopathic REM sleep behavior disorder (RBD) and healthy controls for the purpose of preparing for a clinical trial of neuroprotective treatments against synucleinopathies.