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Progression of atypical parkinsonian syndromes: PROSPECT-M-UK study implications for clinical trials.
Street, Duncan; Jabbari, Edwin; Costantini, Alyssa; Jones, P Simon; Holland, Negin; Rittman, Timothy; Jensen, Marte T; Chelban, Viorica; Goh, Yen Y; Guo, Tong; Heslegrave, Amanda J; Roncaroli, Federico; Klein, Johannes C; Ansorge, Olaf; Allinson, Kieren S J; Jaunmuktane, Zane; Revesz, Tamas; Warner, Thomas T; Lees, Andrew J; Zetterberg, Henrik; Russell, Lucy L; Bocchetta, Martina; Rohrer, Jonathan D; Burn, David J; Pavese, Nicola; Gerhard, Alexander; Kobylecki, Christopher; Leigh, P Nigel; Church, Alistair; Hu, Michele T M; Houlden, Henry; Morris, Huw; Rowe, James B.
Afiliación
  • Street D; University of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, CB2 OQQ, UK.
  • Jabbari E; Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Costantini A; Movement Disorders Centre, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Jones PS; Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Holland N; Movement Disorders Centre, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Rittman T; University of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, CB2 OQQ, UK.
  • Jensen MT; University of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, CB2 OQQ, UK.
  • Chelban V; University of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, CB2 OQQ, UK.
  • Goh YY; Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Guo T; Movement Disorders Centre, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Heslegrave AJ; Department of Neuromuscular Diseases, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Roncaroli F; Neurobiology and Medical Genetics Laboratory, 'Nicolae Testemitanu' State University of Medicine and Pharmacy, Chisinau 2004, Republic of Moldova.
  • Klein JC; Department of Neuromuscular Diseases, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Ansorge O; Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Allinson KSJ; Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Jaunmuktane Z; UK Dementia Research Institute, University College London, London, W1T 7NF, UK.
  • Revesz T; Geoffrey Jefferson Brain Research Centre, Division of Neuroscience, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M6 8HD, UK.
  • Warner TT; Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.
  • Lees AJ; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.
  • Zetterberg H; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.
  • Russell LL; University of Cambridge Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, Cambridge, CB2 OQQ, UK.
  • Bocchetta M; Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Rohrer JD; Queen Square Brain Bank for Neurological Disorders, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Burn DJ; Reta Lila Weston Institute, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Pavese N; Queen Square Brain Bank for Neurological Disorders, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Gerhard A; Reta Lila Weston Institute, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Kobylecki C; Queen Square Brain Bank for Neurological Disorders, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Leigh PN; Reta Lila Weston Institute, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Church A; Queen Square Brain Bank for Neurological Disorders, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Hu MTM; Reta Lila Weston Institute, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Houlden H; Department of Neurodegenerative Disease, University College London, Queen Square Institute of Neurology, London, WC1N 3BG, UK.
  • Morris H; UK Dementia Research Institute, University College London, London, W1T 7NF, UK.
  • Rowe JB; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 431 30 Mölndal, Sweden.
Brain ; 146(8): 3232-3242, 2023 08 01.
Article en En | MEDLINE | ID: mdl-36975168
ABSTRACT
The advent of clinical trials of disease-modifying agents for neurodegenerative disease highlights the need for evidence-based end point selection. Here we report the longitudinal PROSPECT-M-UK study of progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), multiple system atrophy (MSA) and related disorders, to compare candidate clinical trial end points. In this multicentre UK study, participants were assessed with serial questionnaires, motor examination, neuropsychiatric and MRI assessments at baseline, 6 and 12 months. Participants were classified by diagnosis at baseline and study end, into Richardson syndrome, PSP-subcortical (PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (PSP-frontal, PSP-speech and language and PSP-CBS subtypes), MSA-parkinsonism, MSA-cerebellar, CBS with and without evidence of Alzheimer's disease pathology and indeterminate syndromes. We calculated annual rate of change, with linear mixed modelling and sample sizes for clinical trials of disease-modifying agents, according to group and assessment type. Two hundred forty-three people were recruited [117 PSP, 68 CBS, 42 MSA and 16 indeterminate; 138 (56.8%) male; age at recruitment 68.7 ± 8.61 years]. One hundred and fifty-nine completed the 6-month assessment (82 PSP, 27 CBS, 40 MSA and 10 indeterminate) and 153 completed the 12-month assessment (80 PSP, 29 CBS, 35 MSA and nine indeterminate). Questionnaire, motor examination, neuropsychiatric and neuroimaging measures declined in all groups, with differences in longitudinal change between groups. Neuroimaging metrics would enable lower sample sizes to achieve equivalent power for clinical trials than cognitive and functional measures, often achieving N < 100 required for 1-year two-arm trials (with 80% power to detect 50% slowing). However, optimal outcome measures were disease-specific. In conclusion, phenotypic variance within PSP, CBS and MSA is a major challenge to clinical trial design. Our findings provide an evidence base for selection of clinical trial end points, from potential functional, cognitive, clinical or neuroimaging measures of disease progression.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Parálisis Supranuclear Progresiva / Atrofia de Múltiples Sistemas / Trastornos Parkinsonianos Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Brain Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Parálisis Supranuclear Progresiva / Atrofia de Múltiples Sistemas / Trastornos Parkinsonianos Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: Brain Año: 2023 Tipo del documento: Article País de afiliación: Reino Unido