Sleep Disorder Rem Sleep BehaviorNCT04266457
Establishing Alpha-synuclein RT-QuIC Assay as a Diagnostic Technique in REM Sleep Behaviour Disorder
An observational study of Sleep Disorder Rem Sleep Behavior and Parkinson's Disease, Lewy Body, run by University of Edinburgh at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sleep Disorder Rem Sleep Behavior, Parkinson's Disease, Lewy Body
- How many people
- 0 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Sep 2021to 1 Sep 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients diagnosed with REM Sleep Behavioural Disorder using ICSD-3 criteria
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
The University of Edinburgh
Edinburgh, Lothian, EH16 4TJ
About this study
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)
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.
Read the detailed 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.
- Being tested
- No Intervention
- Keywords
- REMBD, REM Behavioural Disorder, prodromal α-synucleinopathies
- Medical subject headings
- REM Sleep Behavior Disorder, Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No InterventionOther
No Intervention
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 0-24 months after sample taken
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2020
- Study start1 Sep 2021 (estimated)
- Primary completion1 Sep 2022 (estimated)
- Study completion1 Sep 2022 (estimated)
Why it stopped: Study stopped after ethical approval but before first patient gave consent due to pandemic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for Sleep Disorder Rem Sleep BehaviorStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Weston Brain Institute
- Responsible party
- Sponsor
- Investigators
- Renata L Riha, MD, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04266457
- Sponsor's protocol ID
- AC20015
- Status last verified
- May 2021
- First submitted
- 10 Feb 2020
- Last updated
- 18 Oct 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 25681454Iranzo 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.
PubMed 23562390Boeve BF, Silber MH, Ferman TJ, Lin SC, Benarroch EE, Schmeichel AM, Ahlskog JE, Caselli RJ, Jacobson S, Sabbagh M, Adler C, Woodruff B, Beach TG, Iranzo A, Gelpi E, Santamaria J, Tolosa E, Singer C, Mash DC, Luca C, Arnulf I, Duyckaerts C, Schenck CH, Mahowald MW, Dauvilliers Y, Graff-Radford NR, Wszolek ZK, Parisi JE, Dugger B, Murray ME, Dickson DW. Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. Sleep Med. 2013 Aug;14(8):754-62. doi: 10.1016/j.sleep.2012.10.015. Epub 2013 Mar 7.
PubMed 23474058Schenck CH, Boeve BF, Mahowald MW. Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med. 2013 Aug;14(8):744-8. doi: 10.1016/j.sleep.2012.10.009. Epub 2013 Jan 22.
PubMed 23347909Plomhause L, Dujardin K, Duhamel A, Delliaux M, Derambure P, Defebvre L, Monaca Charley C. Rapid eye movement sleep behavior disorder in treatment-naive Parkinson disease patients. Sleep Med. 2013 Oct;14(10):1035-7. doi: 10.1016/j.sleep.2013.04.018. Epub 2013 Jul 25.
PubMed 23890957Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003 Mar-Apr;24(2):197-211. doi: 10.1016/s0197-4580(02)00065-9.
PubMed 12498954Kim YK, Yoon IY, Kim JM, Jeong SH, Kim KW, Shin YK, Kim BS, Kim SE. The implication of nigrostriatal dopaminergic degeneration in the pathogenesis of REM sleep behavior disorder. Eur J Neurol. 2010 Mar;17(3):487-92. doi: 10.1111/j.1468-1331.2009.02854.x. Epub 2009 Nov 24.
PubMed 19968708Barber TR, Lawton M, Rolinski M, Evetts S, Baig F, Ruffmann C, Gornall A, Klein JC, Lo C, Dennis G, Bandmann O, Quinnell T, Zaiwalla Z, Ben-Shlomo Y, Hu MTM. Prodromal Parkinsonism and Neurodegenerative Risk Stratification in REM Sleep Behavior Disorder. Sleep. 2017 Aug 1;40(8):zsx071. doi: 10.1093/sleep/zsx071.
PubMed 28472425Puschmann A, Bhidayasiri R, Weiner WJ. Synucleinopathies from bench to bedside. Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S24-7. doi: 10.1016/S1353-8020(11)70010-4.
PubMed 22166445Peelaerts W, Baekelandt V. a-Synuclein strains and the variable pathologies of synucleinopathies. J Neurochem. 2016 Oct;139 Suppl 1:256-274. doi: 10.1111/jnc.13595. Epub 2016 Mar 30.
PubMed 26924014Tyson T, Steiner JA, Brundin P. Sorting out release, uptake and processing of alpha-synuclein during prion-like spread of pathology. J Neurochem. 2016 Oct;139 Suppl 1(Suppl 1):275-289. doi: 10.1111/jnc.13449. Epub 2016 Feb 10.
PubMed 26617280El-Agnaf OM, Salem SA, Paleologou KE, Curran MD, Gibson MJ, Court JA, Schlossmacher MG, Allsop D. Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease. FASEB J. 2006 Mar;20(3):419-25. doi: 10.1096/fj.03-1449com.
PubMed 16507759Tinsley RB, Kotschet K, Modesto D, Ng H, Wang Y, Nagley P, Shaw G, Horne MK. Sensitive and specific detection of alpha-synuclein in human plasma. J Neurosci Res. 2010 Sep;88(12):2693-700. doi: 10.1002/jnr.22417.
PubMed 20648655Foulds PG, Mitchell JD, Parker A, Turner R, Green G, Diggle P, Hasegawa M, Taylor M, Mann D, Allsop D. Phosphorylated alpha-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson's disease. FASEB J. 2011 Dec;25(12):4127-37. doi: 10.1096/fj.10-179192. Epub 2011 Aug 24.
PubMed 21865317Doppler K, Jentschke HM, Schulmeyer L, Vadasz D, Janzen A, Luster M, Hoffken H, Mayer G, Brumberg J, Booij J, Musacchio T, Klebe S, Sittig-Wiegand E, Volkmann J, Sommer C, Oertel WH. Dermal phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as prodromal Parkinson's disease. Acta Neuropathol. 2017 Apr;133(4):535-545. doi: 10.1007/s00401-017-1684-z. Epub 2017 Feb 8.
PubMed 28180961
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04266457
- Acronym / sponsor ID
- AC20015
- Keywords
- REMBD, REM Behavioural Disorder, prodromal α-synucleinopathies
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Study stopped after ethical approval but before first patient gave consent due to pandemic
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- Weston Brain Institute
- Study start
- 1 Sep 2021 (estimated)
- Primary completion
- 1 Sep 2022 (estimated)
- Study completion
- 1 Sep 2022 (estimated)
- First posted
- 12 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients diagnosed with REM Sleep Behavioural Disorder using ICSD-3 criteria
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No InterventionNo Intervention | Other | – |
Primary outcome
Presence of pathological α-synuclein within the cerebrospinal fluid (CSF)
Time frame: 0-24 months after sample taken
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.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2022.
- Background: PubMed 25681454Postuma 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.
- Background: PubMed 23562390Iranzo 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.
- Background: PubMed 23474058Boeve BF, Silber MH, Ferman TJ, Lin SC, Benarroch EE, Schmeichel AM, Ahlskog JE, Caselli RJ, Jacobson S, Sabbagh M, Adler C, Woodruff B, Beach TG, Iranzo A, Gelpi E, Santamaria J, Tolosa E, Singer C, Mash DC, Luca C, Arnulf I, Duyckaerts C, Schenck CH, Mahowald MW, Dauvilliers Y, Graff-Radford NR, Wszolek ZK, Parisi JE, Dugger B, Murray ME, Dickson DW. Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. Sleep Med. 2013 Aug;14(8):754-62. doi: 10.1016/j.sleep.2012.10.015. Epub 2013 Mar 7.
- Background: PubMed 23347909Schenck CH, Boeve BF, Mahowald MW. Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med. 2013 Aug;14(8):744-8. doi: 10.1016/j.sleep.2012.10.009. Epub 2013 Jan 22.
- Background: PubMed 23890957Plomhause L, Dujardin K, Duhamel A, Delliaux M, Derambure P, Defebvre L, Monaca Charley C. Rapid eye movement sleep behavior disorder in treatment-naive Parkinson disease patients. Sleep Med. 2013 Oct;14(10):1035-7. doi: 10.1016/j.sleep.2013.04.018. Epub 2013 Jul 25.
- Background: PubMed 12498954Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003 Mar-Apr;24(2):197-211. doi: 10.1016/s0197-4580(02)00065-9.
- Background: PubMed 19968708Kim YK, Yoon IY, Kim JM, Jeong SH, Kim KW, Shin YK, Kim BS, Kim SE. The implication of nigrostriatal dopaminergic degeneration in the pathogenesis of REM sleep behavior disorder. Eur J Neurol. 2010 Mar;17(3):487-92. doi: 10.1111/j.1468-1331.2009.02854.x. Epub 2009 Nov 24.
- Background: PubMed 28472425Barber TR, Lawton M, Rolinski M, Evetts S, Baig F, Ruffmann C, Gornall A, Klein JC, Lo C, Dennis G, Bandmann O, Quinnell T, Zaiwalla Z, Ben-Shlomo Y, Hu MTM. Prodromal Parkinsonism and Neurodegenerative Risk Stratification in REM Sleep Behavior Disorder. Sleep. 2017 Aug 1;40(8):zsx071. doi: 10.1093/sleep/zsx071.
- Background: PubMed 22166445Puschmann A, Bhidayasiri R, Weiner WJ. Synucleinopathies from bench to bedside. Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S24-7. doi: 10.1016/S1353-8020(11)70010-4.
- Background: PubMed 26924014Peelaerts W, Baekelandt V. a-Synuclein strains and the variable pathologies of synucleinopathies. J Neurochem. 2016 Oct;139 Suppl 1:256-274. doi: 10.1111/jnc.13595. Epub 2016 Mar 30.
- Background: PubMed 26617280Tyson T, Steiner JA, Brundin P. Sorting out release, uptake and processing of alpha-synuclein during prion-like spread of pathology. J Neurochem. 2016 Oct;139 Suppl 1(Suppl 1):275-289. doi: 10.1111/jnc.13449. Epub 2016 Feb 10.
- Background: PubMed 16507759El-Agnaf OM, Salem SA, Paleologou KE, Curran MD, Gibson MJ, Court JA, Schlossmacher MG, Allsop D. Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease. FASEB J. 2006 Mar;20(3):419-25. doi: 10.1096/fj.03-1449com.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Renata L Riha, MD principal investigator
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sleep Disorder Rem Sleep Behavior and Parkinson's Disease, Lewy Body, run by University of Edinburgh at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Presence of pathological α-synuclein within the cerebrospinal fluid (CSF) (time frame: 0-24 months after sample taken). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04266457, which also lists 24 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2022.