The TOPAZ study: a home-based trial of zoledronic acid to prevent fractures in neurodegenerative parkinsonism

Tanner, Caroline M.; Cummings, Steven R.; Schwarzschild, Michael A.; Brown, Ethan G.; Dorsey, E. Ray; Espay, Alberto J.; Galifianakis, Nicholas B.; Goldman, Samuel; Litvan, Irene; Luthra, Nijee; McFarland, Nikolaus R.; Mitchell, Kyle T.; Standaert, David G.; Bauer, Douglas C.; Greenspan, Susan L.; Beck, James C.; Lyles, Kenneth W.

doi:10.1038/s41531-021-00162-1

Cited by 12 publications

(11 citation statements)

References 29 publications

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“…15 Commensurate with the lower effect sizes of lower-risk interventions, such trials would require larger sample sizes, but may be amendable to innovative trial designs such as remote/virtual trials, which can enroll larger cohorts. 26…”

Section: Targets and Potential Therapeuticsmentioning

confidence: 99%

Who to Enroll in Parkinson Disease Prevention Trials?

2022

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Therapies that prevent the occurrence of Parkinson disease (PD) (primary prevention) or mitigate the progression of symptoms in those with early disease (secondary prevention) are a critical unmet need in disease management. Despite great promise, PD prevention trials have not yet demonstrated success. Initiation of treatment too late in the disease course and the heterogeneity of disease are obstacles that may have contributed to the failure. Genetically stratified groups offer many advantages to primary and secondary prevention trials. In addition to their ease of identification, they decrease disease heterogeneity on several levels. Particularly, they comprise a phenotypically and pathologically enriched group with defined clinical features, pathogenic mechanisms and associated proteins that may serve as specific trial endpoints, therapeutic targets and biomarkers for disease state, and pharmacodynamic and pharmacokinetic status. However, challenges arise from genetic variant heterogeneity, from reduced penetrance whereby many carriers will not develop PD, and in recruiting a population that will meet the desired outcome in the proposed study duration. In this review, we discussed the opportunities afforded by the enrollment of genetically stratified cohorts (i.e., leucine-rich repeat kinase 2 and glucocerebrosidase 1) into prevention trials with a primary focus on primary prevention trials. We also outlined challenges surrounding the enrollment of these cohorts and offered suggestions to leverage their many advantages.

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Section: Targets and Potential Therapeuticsmentioning

confidence: 99%

Who to Enroll in Parkinson Disease Prevention Trials?

2022

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“…The TOPAZ trial was a home-based trial evaluating the efficacy of zolendronic acid in preventing fractures in elderly patients with Parkinson's disease [ 30 ]. The virtual format of this trial with recruitment via support groups and websites, online consenting, diagnosis through telemedicine, administration of home-based therapy via research nurses, and assessment of endpoints by surveying electronic health records or follow-up via mail, e-mail or phone every 6 months made the trial feasible in a population which might otherwise have not been able to participate in a site-centric trial due to mobility issues.…”

Section: Examples Of Virtual Trialsmentioning

confidence: 99%

Virtual oncology research-different models and lessons learned

Ranganathan

Pramesh

2022

Current Opinion in Supportive &Amp; Palliative Care

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Purpose of reviewThe COVID-19 pandemic posed several challenges to cancer research including halting of trials, reduced recruitment and protocol violations related to inflexible processes followed in clinical trials. Researchers adopted innovative measures to mitigate these problems and continue studies without compromising their quality. This review collates these adaptations that could well continue after the pandemic. Recent findingsThe COVID-19 pandemic forced researchers globally to adopt innovative measures to overcome the challenges of the pandemic. These included protocol amendments to adjust to the pandemic and travel restrictions, and increased use of digital technologies. 'Virtual' clinical trials were conducted increasingly with adaptations in ethics and regulatory approvals, patient recruitment and consenting, study interventions and delivery of study medications, trial assessments, and monitoring. Many of these adaptations are safe and feasible, without compromising study quality and data integrity. Although these may not be universally applicable in all types of research, they bring many benefits including more diverse patient participation, less burden on patients for study procedures and reduced resources to conduct trials.

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“…We need to create a culture in which we can honestly and openly weigh trade‐offs between ethical and scientific principles. Only a handful of Parkinson's trials list language as an inclusion or exclusion requirement 24,25 . Trials should a priori plan for whether they will (a) specifically seek to enroll these participants, (b) accommodate them if they present, (c) make site‐dependent decisions, or (d) exclude them.…”

Section: Proposed Solutions To Increase Inclusion Of Non–english‐spea...mentioning

confidence: 99%

“…Only a handful of Parkinson's trials list language as an inclusion or exclusion requirement. 24,25 Trials should a priori plan for whether they will (a) specifically seek to enroll these participants, (b) accommodate them if they present, (c) make sitedependent decisions, or (d) exclude them. The tradeoffs we have laid out should be explicitly explored and justified in study protocols.…”

Section: Earliest Possible Opportunity To Consider Justicementioning

confidence: 99%