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Study stopped after ethical approval but before first patient gave consent due to pandemic
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| Name | Class |
|---|---|
| Weston Brain Institute | OTHER |
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We hypothesise that a real-time quaking induced conversion assay for the detection of pathological alpha-synuclein (α -syn RTQuIC) can be used to differentiate between cases of idiopathic REM-sleep behaviour disorder (RBD) and RBD that is symptomatic of prodromal α-synucleinopathies.
This study will be the largest analysis of cerebrospinal fluid (CSF) α-synuclein in Rapid Eye Movement Behaviour Disorder (RBD) patients to date. In line with the The National CJD Research & Surveillance Unit (NCJDRSU)'s recent inclusion of a positive RT-QuIC for pathological prion protein in the diagnostic criteria for Creutzfeldt-Jakob Disease (CJD) [1], we aim to deploy this novel method to establish it as an accurate research and diagnostic resource in the assessment and prognosis of RBD. This research is transformative and has the potential to change practice.
Currently, there is no simple method with high sensitivity and specificity available which can identify patients who will go on to develop an α - synucleinopathy. Clinical assessment of a panel of markers (e.g. Postuma et al. 2015) are time-consuming and impractical in normal clinical settings, with the majority of patients presenting to sleep physicians, geriatricians, and non-specialised neurology clinics, both publicly and privately. This has a major impact on counselling strategies for RBD patients, appropriate follow-up, trials of novel neuro-protective agents in alpha-synucleinopathies before full-blown phenotype is manifest and enhancing understanding of pathways involved in RBD out-with the dopaminergic system.
RBD is a common, sometimes fatal disease (through injury to self/others) and treatments are indiscriminate regarding aetiology with limited evidence-base. A simple test using CSF (analogous to measuring CSF-orexin levels to diagnose narcolepsy+cataplexy) with high sensitivity and specificity is ideal. Thus, we believe that the central thesis of our work will not only inform subsequent behavioural, genetic and neuroimaging characterisation of our established RBD cohort, but will also translate the α-syn RT-QuIC concept into evidence-based and effective clinical practice.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| No Intervention | Other | No Intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Presence of pathological α-synuclein within the cerebrospinal fluid (CSF) | The primary outcome measure will be either a positive/negative (binary) result from the α-syn RT-QuIC assay. A positive output confirms presence of pathological α-synuclein within the CSF. | 0-24 months after sample taken |
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Inclusion Criteria:
Exclusion Criteria:
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Patients diagnosed with REM Sleep Behavioural Disorder using ICSD-3 criteria
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| Name | Affiliation | Role |
|---|---|---|
| Renata L Riha, MD | University of Edinburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Edinburgh | Edinburgh | Lothian | EH16 4TJ | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25681454 | Background | Postuma RB, Gagnon JF, Bertrand JA, Genier Marchand D, Montplaisir JY. Parkinson risk in idiopathic REM sleep behavior disorder: preparing for neuroprotective trials. Neurology. 2015 Mar 17;84(11):1104-13. doi: 10.1212/WNL.0000000000001364. Epub 2015 Feb 13. | |
| 23562390 | Background | Iranzo A, Tolosa E, Gelpi E, Molinuevo JL, Valldeoriola F, Serradell M, Sanchez-Valle R, Vilaseca I, Lomena F, Vilas D, Llado A, Gaig C, Santamaria J. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet Neurol. 2013 May;12(5):443-53. doi: 10.1016/S1474-4422(13)70056-5. Epub 2013 Apr 3. |
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| ID | Term |
|---|---|
| D020187 | REM Sleep Behavior Disorder |
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020923 | REM Sleep Parasomnias |
| D020447 | Parasomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
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5ml ceberospinal fluid, 9ml blood
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| D001523 |
| Mental Disorders |
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |