Establishing Alpha-synuclein RT-QuIC Assay as a Diagnostic Technique in REM Sleep Behaviour Disorder

Parkinson's Disease, Lewy Body Clinical Trial

Official title:

Establishing Alpha-synuclein Real Time - Quaking Induced Conversion (RT-QuIC) Assay as a Diagnostic Technique in Rapid Eye Movement (REM) Sleep Behaviour Disorder (RBD)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04266457
• Other study ID #: AC20015
• Status: Withdrawn
• Start date: September 1, 2021
• Est. completion date: September 1, 2022

Study information

• Verified date: May 2021
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 1, 2022
• Est. primary completion date: September 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients diagnosed with Rapid Eye Movement Behaviour Disorder (RBD) using the International Classification of Sleep Disorders version 3 (ICSD-3) criteria [18] - Patients aged 18 years and over - Patient able to give written informed consent

Exclusion Criteria:

• RBD secondary to medication or withdrawal state. - <18 years old - Inability to give written informed consent - Contraindication to lumbar puncture procedure (e.g. patients taking Warfarin)

Related Conditions & MeSH terms

• Disease
• Mental Disorders
• Parkinson Disease
• Parkinson's Disease, Lewy Body
• REM Sleep Behavior Disorder
• Sleep Disorder Rem Sleep Behavior
• Sleep Wake Disorders

Intervention

Other:
• No Intervention
No Intervention

Locations

Country	Name	City	State
United Kingdom	The University of Edinburgh	Edinburgh	Lothian

Sponsors (2)

Lead Sponsor	Collaborator
University of Edinburgh	Weston Brain Institute

Country where clinical trial is conducted

United Kingdom, 

References & Publications (24)

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* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of pathological a-synuclein within the cerebrospinal fluid (CSF)	The primary outcome measure will be either a positive/negative (binary) result from the a-syn RT-QuIC assay. A positive output confirms presence of pathological a-synuclein within the CSF.	0-24 months after sample taken