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

Abstract

The Trial of Parkinson's And Zoledronic acid (TOPAZ, https://ichgcp.net/clinical-trials-registry/NCT03924414 ) is a unique collaboration between experts in movement disorders and osteoporosis to test the efficacy of zoledronic acid, an FDA-approved parenteral treatment for osteoporosis, for fracture prevention in people with neurodegenerative parkinsonism. Aiming to enroll 3,500 participants age 65 years or older, TOPAZ is one of the largest randomized, placebo-controlled clinical trials ever attempted in parkinsonism. The feasibility of TOPAZ is enhanced by its design as a U.S.- wide home-based trial without geographical limits. Participants receive information from multiple sources, including specialty practices, support groups and websites. Conducting TOPAZ in participants' homes takes advantage of online consent technology, the capacity to confirm diagnosis using telemedicine and the availability of research nursing to provide screening and parenteral therapy in homes. Home-based clinical research may provide an efficient, convenient, less expensive method that opens participation in clinical trials to almost anyone with parkinsonism.

Conflict of interest statement

Caroline M. Tanner receives grants from the Michael J. Fox Foundation, the Parkinson’s Foundation, the Department of Defense, BioElectron, Roche/Genentech, Biogen Idec and the National Institutes of Health, compensation for serving on Data Monitoring Committees from Voyager Therapeutics, Intec Pharma and Cadent Therapeutics and personal fees for consulting from Neurocrine Biosciences, Adamas Therapeutics, Grey Matter, Acorda, Acadia, Amneal, Lundbeck and CNS Ratings. Steven R. Cummings Receives consulting and grant support from Amgen and Radius and consulting from UCB Pharma. Michael A. Schwarzschild has within the past three years received funding from the Cure Parkinson’s Trust, CBD Solutions trust, Michael J. Fox Foundation for Parkinson’s Research (MJFF), Prevail Therapeutics, Denali Therapeutics and nQ Medical for serving on their scientific advisory boards; from Eli Lilly and Company for serving on a trial Data Monitoring Committee; from Biotie Therapeutics, Inc./Acorda Therapeutics, MJFF, Parkinson’s Foundation and Univ. of California-San Francisco for serving on study steering committees; and from Denali Therapeutics for presenting a seminar. He has within the past three years received research funding from the NIH, Parkinson’s Foundation, U.S. Department of Defense, RJG Foundation, Target ALS Foundation, MJFF and the Farmer Family Foundation. Ethan G. Brown receives research support from the Michael J. Fox Foundation, Biogen Idec, and the Gateway Institute for Brain Science. He receives honorarium from NEJM Knowledge+ for his role as the Neurology Section Editor. He also has received personal fees for consulting from Oscar Insurance Corporation and Rune Labs. E Ray Dorsey has served as a consultant to 23andMe, Abbott, Abbvie, Amwell, Biogen, Clintrex, CuraSen, DeciBio, Denali Therapeutics, GlaxoSmithKline, Grand Rounds, Huntington Study Group, Informa Pharma Consulting, medical-legal services, Mednick Associates, Medopad, Olson Research Group, Origent Data Sciences, Inc., Pear Therapeutics, Prilenia, Roche, Sanofi, Shire, Spark Therapeutics, Sunovion Pharmaceuticals, Voyager Therapeutics, and ZS Consulting. He has received honoraria from the Alzheimer’s Drug Discovery Foundation, American Academy of Neurology, American Neurological Association, California Pacific Medical Center, Excellus BlueCross BlueShield, Food and Drug Administration, MCM Education, Michael J. Fox Foundation, Stanford University, UC Irvine, and University of Michigan. He has received research support from Abbvie, Acadia Pharmaceuticals, AMC Health, BioSensics, Burroughs Wellcome Fund, Greater Rochester Health Foundation, Huntington Study Group, Michael J. Fox Foundation, National Institutes of Health, Nuredis, Inc., Patient-Centered Outcomes Research Institute, Pfizer, PhotoPharmics, Roche, and the Safra Foundation. Dr. Dorsey provides editorial services for Karger Publications has ownership interests in Grand Rounds, an online second opinion service. Alberto J. Espay has received grant support from the NIH and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Abbvie, Neuroderm, Neurocrine, Amneal, Adamas, Acadia, Acorda, InTrance, Sunovion, Lundbeck, and USWorldMeds; publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer; and honoraria from USWorldMeds, Acadia, and Sunovion. Nicholas B. Galifianakis receives grant support from the National Institutes of Health and the Boston Scientific Corporation. Samuel M. Goldman receives grant support from Michael J. Fox Foundation, the Department of Defense, Biogen Idec, the National Institutes of Health, the Agency for Toxic Substances and Disease Registry, the American Academy of Pediatrics, the National Institute of Occupational Safety and Health, the Health Resources and Services Administration, and the Veterans Administration Office of Research and Development. Irene Litvan research is supported by the National Institutes of Health grants: 5P50AG005131-33, 2R01AG038791-06A, U01NS090259, U01NS100610, U01NS80818, R25NS098999, P20GM109025; U19 AG063911-1; Parkinson Study Group, Michael J Fox Foundation, Parkinson Foundation, Lewy Body Association, Roche, Abbvie, Biogen, EIP-Pharma and Biohaven Pharmaceuticals. She was member of a Lundbeck Advisory Board and participated in a symposium organized by Sunovion. She receives her salary from the University of California San Diego and as Chief Editor of Frontiers in Neurology. Nijee Luthra has no disclosures. Nicholas McFarland has received grant support from the NIH and the Michael J. Fox Foundation, and served as a consultant to AbbVie. He supported by an endowment and University funds. Kyle Mitchell has consulted for Boston Scientific Corporation and Rune Labs, Inc. David Standaert is a member of the faculty of the University of Alabama at Birmingham and is supported by endowment and University funds. Dr. Standaert is an investigator in studies funded by Abbvie, Inc., Avid Radiopharmaceuticals, the American Parkinson Disease Association, the Michael J. Fox Foundation for Parkinson Research, Alabama Department of Commerce, the Department of Defense, and NIH grants P01NS087997, P50NS108675, R25NS079188, P2CHD086851, P30NS047466, and T32NS095775. He has a clinical practice and is compensated for these activities through the University of Alabama Health Services Foundation. In addition, since January 1, 2019 he has served as a consultant for or received honoraria from Axovant Sciences, Inc., Censa Pharmaceuticals, Abbvie Inc., Grey Matter Technologies, Theravance Inc., the Kennedy Krieger Institute, McGraw Hill Publishers, Sanofi- Aventis, RTI Consultants, Cerevance Inc., Yale University and Michigan State University. Douglas Bauer has no disclosures. Susan L. Greenspan receives research support from Amgen and Radius. James Beck is an employee of the Parkinson’s Foundation. Kenneth W. Lyles: Founder and Equity Owner of Faculty Connections, LLC; Member of the Board of Trustees of the National Osteoporosis Foundations; Inventor or Co-inventor of patents involving the use of zoledronic acid.

Figures

Fig. 1. Meta-analysis of the Association of Hip Fracture in People with Parkinson’s Disease.

The forest plot shows effect sizes and 95% confidence intervals for individual studies, showing an overall estimated increased risk of hip fracture, determined from health records or by self report, in people with Parkinson’s disease. Adapted from Schini et al 2020 with permission.

Fig. 2. Flow of Participation in TOPAZ Study.

Participants may self-refer or be referred by neurologists. Informed consent is provided online and treatment is provided in the home. Followup isconducted remotely.