Dokumentdetails
ID
oai:pubmedcentral.nih.gov:1067...
Thema
ProtocolAutor
Colucci, Fabiana Avenali, Micol De Micco, Rosita Fusar Poli, Marco Cerri, Silvia Stanziano, Mario Bacila, Ana Cuconato, Giada Franco, Valentina Franciotta, Diego Ghezzi, Cristina Gastaldi, Matteo Elia, Antonio Emanuele Romito, Luigi Devigili, Grazia Leta, Valentina Garavaglia, Barbara Golfrè Andreasi, Nico Cazzaniga, Federico Reale, Chiara Galandra, Caterina Germani, Giancarlo Mitrotti, Pierfrancesco Ongari, Gerardo Palmieri, Ilaria Picascia, Marta Pichiecchio, Anna Verri, Mattia Esposito, Fabrizio Cirillo, Mario Di Nardo, Federica Aloisio, Simone Siciliano, Mattia Prioni, Sara Amami, Paolo Piacentini, Sylvie Bruzzone, Maria Grazia Grisoli, Marina Moda, Fabio Eleopra, Roberto Tessitore, Alessandro Valente, Enza Maria Cilia, RobertoLangue
enEditor
BMJ Publishing Group
Kategorie
BMJ Neurology Open
Jahr
2023
Auflistungsdatum
13.12.2023
Schlüsselwörter
disease risk abx study 52 weeks trialZusammenfassung
BACKGROUND: Heterozygous mutations in the GBA gene, encoding the lysosomal enzyme β-glucocerebrosidase (GCase), are the most frequent genetic risk factor for Parkinson’s disease (PD).
GBA-related PD (GBA-PD) patients have higher risk of dementia and reduced survival than non-carriers.
Preclinical studies and one open-label trial in humans demonstrated that the chaperone ambroxol (ABX) increases GCase levels and modulates α-synuclein levels in the blood and cerebrospinal fluid (CSF).
METHODS AND ANALYSIS: In this multicentre, double-blind, placebo-controlled, phase II clinical trial, we randomise patients with GBA-PD in a 1:1 ratio to either oral ABX 1.2 g/day or placebo.
The duration of treatment is 52 weeks.
Each participant is assessed at baseline and weeks 12, 26, 38, 52 and 78.
Changes in the Montreal Cognitive Assessment score and the frequency of mild cognitive impairment and dementia between baseline and weeks 52 are the primary outcome measures.
Secondary outcome measures include changes in validated scales/questionnaires assessing motor and non-motor symptoms.
Neuroimaging features and CSF neurodegeneration markers are used as surrogate markers of disease progression.
GCase activity, ABX and α-synuclein levels are also analysed in blood and CSF.
A repeated-measures analysis of variance will be used for elaborating results.
The primary analysis will be by intention to treat.
ETHICS AND DISSEMINATION: The study and protocols have been approved by the ethics committee of centres.
The study is conducted according to good clinical practice and the Declaration of Helsinki.
The trial findings will be published in peer-reviewed journals and presented at conferences.
TRIAL REGISTRATION NUMBERS: NCT05287503, EudraCT 2021-004565-13.
Colucci, Fabiana,Avenali, Micol,De Micco, Rosita,Fusar Poli, Marco,Cerri, Silvia,Stanziano, Mario,Bacila, Ana,Cuconato, Giada,Franco, Valentina,Franciotta, Diego,Ghezzi, Cristina,Gastaldi, Matteo,Elia, Antonio Emanuele,Romito, Luigi,Devigili, Grazia,Leta, Valentina,Garavaglia, Barbara,Golfrè Andreasi, Nico,Cazzaniga, Federico,Reale, Chiara,Galandra, Caterina,Germani, Giancarlo,Mitrotti, Pierfrancesco,Ongari, Gerardo,Palmieri, Ilaria,Picascia, Marta,Pichiecchio, Anna,Verri, Mattia,Esposito, Fabrizio,Cirillo, Mario,Di Nardo, Federica,Aloisio, Simone,Siciliano, Mattia,Prioni, Sara,Amami, Paolo,Piacentini, Sylvie,Bruzzone, Maria Grazia,Grisoli, Marina,Moda, Fabio,Eleopra, Roberto,Tessitore, Alessandro,Valente, Enza Maria,Cilia, Roberto, 2023, Ambroxol as a disease-modifying treatment to reduce the risk of cognitive impairment in GBA-associated Parkinson’s disease: a multicentre, randomised, double-blind, placebo-controlled, phase II trial. The AMBITIOUS study protocol, BMJ Publishing Group
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