Objective: To report on the selection of an imaging biomarker for a sub-study in a multi-arm, multi-stage (MAMS) platform trial for disease-modifying therapies (DMTs) in Parkinson’s disease (PD).

Background: A growing number of biomarkers have shown promise in tracking disease progression in PD. Of those, imaging techniques present advantages such as non-invasiveness and a low burden on people with PD.

The Edmond J Safra Accelerating Clinical Trials in PD (EJS ACT-PD) initiative designed a phase 3 MAMS platform trial for DMTs in PD, including biomarker sub-studies.

Method: An Imaging Subgroup was created as part of the Outcome Measure Working Group, comprising imaging experts, core trial staff, and patient and public involvement and engagement representatives. The most relevant imaging candidates were discussed in meetings and online communications. Imaging protocols were created, with attention to scientific relevance and practical issues.

Results: Positron emission tomography, single photon emission computerized tomography (SPECT) and magnetic resonance (MR) spectroscopy were deprioritised in the first instance primarily due to costs and limited availability. Dopamine transporter SPECT (DaT-SPECT) was also deemed less likely to track disease progression in established PD.

MR imaging (MRI) was selected due to its feasibility (availability, costs), patient acceptability (safety and non-invasiveness), and scientific evidence on its ability to track disease progression.

Two MRI protocols (20 and 60 minutes) were designed, to increase the acceptability and feasibility of the sub-study. All acquisitions will be isotropic and acquired using 3T MRI. The shorter one is for basic quantification of brain structure including T1w MPRAGE, T2w and multishell diffusion weighted imaging. The longer one provides more detailed measures of tissue microstructure (e.g., iron, myelin, free water) via multiparametric mapping (quantitative magnetisation transfer, proton density, R2* and R1 maps), quantitative susceptibility mapping, and arterial spin labelling.

MRI data will be collected from consenting participants at baseline, 18 and 36 months after trial randomisation.

Conclusion: We present two MRI protocols and a provisional imaging sub-study design to explore and further validate MRI as an optimal imaging biomarker in trials of DMTs in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/selecting-an-imaging-biomarker-for-a-multi-arm-multi-stage-trial-of-disease-modifying-treatments-for-parkinsons-the-ejs-act-pd-experience/