Introduction: Reviews of randomized clinical trials (RCTs) in dementia with Lewy bodies (DLB) are essential for informing ongoing research efforts of symptomatic therapies and potentially disease-modifying therapies (DMTs).

Methods: We performed a systematic review of all clinical trials conducted until September 27, 2022, by examining 3 international registries: ClinicalTrials.gov, the European Union Drug Regulating Authorities Clinical Trials Database, and the International Clinical Trials Registry Platform, to identify drugs in trials in DLB.

Results: We found 25 agents in 40 trials assessing symptomatic treatments and DMTs for DLB: 7 phase 3, 31 phase 2, and 2 phase 1 trials. We found an active pipeline for drug development in DLB, with most ongoing clinical trials in phase 2. We identified a recent trend towards including participants at the prodromal stages, although more than half of active clinical trials will enroll mild to moderate dementia patients. Additionally, repurposed agents are frequently tested, representing 65% of clinical trials.

Conclusion: Current challenges in DLB clinical trials include the need for disease-specific outcome measures and biomarkers, and improving representation of global and diverse populations.

Carla Abdelnour has received the Sue Berghoff LBD Research Fellowship, and honoraria as speaker from F. Hoffmann-La Roche Ltd, Zambon, Nutricia, Schwabe Farma Ibérica S.A.U. She is member of the Board of Directors of the Lewy Body Dementia Association. Maria Camila Gonzalez has no conflicts of interest. Lucy L. Gibson has no conflicts of interest. Kathleen L. Poston has been funded by grants to conduct research from the Michael J Fox Foundation for Parkinson’s Research, the Lewy Body Dementia Association, the Alzheimer’s Drug Discovery Foundation, the Sue Berghoff LBD Research Fellowship, and the NIH. She is on the Scientific Advisory Board for Curasen, where she receives consulting fees and stock options. She is on the Scientific Advisory Board for Amprion, where she receives stock options. Clive G. Ballard has received consulting fees from Acadia pharmaceutical company, AARP, Addex pharmaceutical company, Eli Lily, Enterin pharmaceutical company, GWPharm, H.Lundbeck pharmaceutical company, Novo Nordisk pharmaceutical company, Novartis pharmaceutical company, Janssen Pharmaceuticals, Johnson and Johnson pharmaceuticals, Orion Corp pharmaceutical company, Otsuka America Pharm Inc, Sunovion Pharm. Inc, Suven pharmaceutical company, Roche pharmaceutical company, Biogen pharmaceutical company, Synexus clinical research organization and tauX pharmaceutical company. Jeffrey L. Cummings has provided consultation to Acadia, Actinogen, Alkahest, AlphaCognition, AriBio, Biogen, BioVie, Cassava, Cerecin, Corium, Cortexyme, Diadem, EIP Pharma, Eisai, GemVax, Genentech, Green Valley, GAP Innovations, Grifols, Janssen, Karuna, Lilly, Lundbeck, LSP, Merck, NervGen, Novo Nordisk, Oligomerix, Optoceutics, Ono, Otsuka, PRODEO, Prothena, ReMYND, Resverlogix, Roche, Sage Therapeutics, Signant Health, Simcere, Sunbird Bio, Suven, TrueBinding, and Vaxxinity pharmaceutical, assessment, and investment companies. Dag Aarsland has received research support and/or honoraria from Evonik, DailyColors, Muhdo, Astra-Zeneca, H. Lundbeck, Novartis Pharmaceuticals, Sanofi, Roche Diagnostics, and GE Health, and served as paid consultant for H. Lundbeck, Eisai, Heptares, Mentis Cura, Eli Lilly, Anavex, Cognetivity, Enterin, Acadia, Sygnature, Biogen, Cognetivity, EIP Pharma, and Acadia.

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