Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial

Abstract Background Dopamine transporter single-photon emission computed tomography (DaT-SPECT) can quantify the functional integrity of the dopaminergic nerve terminals and has been suggested as an imaging modality to verify the clinical diagnosis of Parkinson’s disease (PD). Depending on the stage...

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Autores principales:	R. Matthew Hutchison, Karleyton C. Evans, Tara Fox, Minhua Yang, Jerome Barakos, Barry J. Bedell, Jesse M. Cedarbaum, Miroslaw Brys, Andrew Siderowf, Anthony E. Lang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Biomarker Dopamine transporter Parkinson’s disease SPECT SWEDD Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/0488346b56e840c7bd83cdfb6e977f97
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spelling	oai:doaj.org-article:0488346b56e840c7bd83cdfb6e977f972021-11-28T12:11:24ZEvaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial10.1186/s12883-021-02470-81471-2377https://doaj.org/article/0488346b56e840c7bd83cdfb6e977f972021-11-01T00:00:00Zhttps://doi.org/10.1186/s12883-021-02470-8https://doaj.org/toc/1471-2377Abstract Background Dopamine transporter single-photon emission computed tomography (DaT-SPECT) can quantify the functional integrity of the dopaminergic nerve terminals and has been suggested as an imaging modality to verify the clinical diagnosis of Parkinson’s disease (PD). Depending on the stage of progression, approximately 5–15% of participants clinically diagnosed with idiopathic PD have been observed in previous studies to have normal DaT-SPECT patterns. However, the utility of DaT-SPECT in enhancing early PD participant selection in a global, multicenter clinical trial of a potentially disease-modifying therapy is not well understood. Methods The SPARK clinical trial was a phase 2 trial of cinpanemab, a monoclonal antibody against alpha-synuclein, in participants with early PD. DaT-SPECT was performed at screening to select participants with DaT-SPECT patterns consistent with degenerative parkinsonism. Acquisition was harmonised across 82 sites. Images were reconstructed and qualitatively read at a central laboratory by blinded neuroradiologists for inclusion prior to automated quantitative analysis. Results In total, 482 unique participants were screened between January 2018 and May 2019; 3.8% (15/398) of imaged participants were excluded owing to negative DaT-SPECT findings (i.e., scans without evidence of dopaminergic deficit [SWEDD]). Conclusion A smaller proportion of SPARK participants were excluded owing to SWEDD status upon DaT-SPECT screening than has been reported in prior studies. Further research is needed to understand the reasons for the low SWEDD rate in this study and whether these results are generalisable to future studies. If supported, the radiation risks, imaging costs, and operational burden of DaT-SPECT for enrichment may be mitigated by clinical assessment and other study design aspects. Trial registration ClinicalTrials.gov identifier: NCT03318523 . Date submitted: October 19, 2017. First Posted: October 24, 2017.R. Matthew HutchisonKarleyton C. EvansTara FoxMinhua YangJerome BarakosBarry J. BedellJesse M. CedarbaumMiroslaw BrysAndrew SiderowfAnthony E. LangBMCarticleBiomarkerDopamine transporterParkinson’s diseaseSPECTSWEDDNeurology. Diseases of the nervous systemRC346-429ENBMC Neurology, Vol 21, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biomarker Dopamine transporter Parkinson’s disease SPECT SWEDD Neurology. Diseases of the nervous system RC346-429
spellingShingle	Biomarker Dopamine transporter Parkinson’s disease SPECT SWEDD Neurology. Diseases of the nervous system RC346-429 R. Matthew Hutchison Karleyton C. Evans Tara Fox Minhua Yang Jerome Barakos Barry J. Bedell Jesse M. Cedarbaum Miroslaw Brys Andrew Siderowf Anthony E. Lang Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial
description	Abstract Background Dopamine transporter single-photon emission computed tomography (DaT-SPECT) can quantify the functional integrity of the dopaminergic nerve terminals and has been suggested as an imaging modality to verify the clinical diagnosis of Parkinson’s disease (PD). Depending on the stage of progression, approximately 5–15% of participants clinically diagnosed with idiopathic PD have been observed in previous studies to have normal DaT-SPECT patterns. However, the utility of DaT-SPECT in enhancing early PD participant selection in a global, multicenter clinical trial of a potentially disease-modifying therapy is not well understood. Methods The SPARK clinical trial was a phase 2 trial of cinpanemab, a monoclonal antibody against alpha-synuclein, in participants with early PD. DaT-SPECT was performed at screening to select participants with DaT-SPECT patterns consistent with degenerative parkinsonism. Acquisition was harmonised across 82 sites. Images were reconstructed and qualitatively read at a central laboratory by blinded neuroradiologists for inclusion prior to automated quantitative analysis. Results In total, 482 unique participants were screened between January 2018 and May 2019; 3.8% (15/398) of imaged participants were excluded owing to negative DaT-SPECT findings (i.e., scans without evidence of dopaminergic deficit [SWEDD]). Conclusion A smaller proportion of SPARK participants were excluded owing to SWEDD status upon DaT-SPECT screening than has been reported in prior studies. Further research is needed to understand the reasons for the low SWEDD rate in this study and whether these results are generalisable to future studies. If supported, the radiation risks, imaging costs, and operational burden of DaT-SPECT for enrichment may be mitigated by clinical assessment and other study design aspects. Trial registration ClinicalTrials.gov identifier: NCT03318523 . Date submitted: October 19, 2017. First Posted: October 24, 2017.
format	article
author	R. Matthew Hutchison Karleyton C. Evans Tara Fox Minhua Yang Jerome Barakos Barry J. Bedell Jesse M. Cedarbaum Miroslaw Brys Andrew Siderowf Anthony E. Lang
author_facet	R. Matthew Hutchison Karleyton C. Evans Tara Fox Minhua Yang Jerome Barakos Barry J. Bedell Jesse M. Cedarbaum Miroslaw Brys Andrew Siderowf Anthony E. Lang
author_sort	R. Matthew Hutchison
title	Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial
title_short	Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial
title_full	Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial
title_fullStr	Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial
title_full_unstemmed	Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial
title_sort	evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 parkinson’s disease trial
publisher	BMC
publishDate	2021
url	https://doaj.org/article/0488346b56e840c7bd83cdfb6e977f97
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Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial

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