Trial of Parkinson's and Zoledronic Acid (TOPAZ)

TOPAZ: Trial of Parkinson's and Zoledronic Acid a Randomized Placebo-controlled Trial of Zoledronic Acid for the Prevention of Fractures in Patients with Parkinson's Disease

This home-based study is a randomized (1:1) placebo-controlled trial of a single infusion of zoledronic acid-5 mg (ZA) for the prevention of fractures in men and women aged 60 years and older with Parkinson's disease and parkinsonism with at least 2 years of follow-up. A total of 2650 participants will be enrolled and randomized in the United States. Participants, follow-up outcome assessors, and study investigators will be blinded to assigned study treatment. This trial is funded by the National Institute of Aging.

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson Disease; Osteoporosis; Parkinsonism; Multiple System Atrophy; Progressive Supranuclear Palsy; Parkinson's Disease and Parkinsonism; Atypical Parkinsonism; Vascular Parkinsonism; Dementia with Lewy Bodies
• Intervention / Treatment: Drug: Zoledronic Acid 5Mg/Bag 100Ml Inj; Other: Placebo

Detailed Description

This home-based randomized clinical trial is designed to test the efficacy of ZA-5 mg in Parkinson's disease (PD) and parkinsonism patients. This trial will also address barriers to treatment of patients with PD and parkinsonism by providing rigorous evidence about whether ZA reduces fracture risk in patients with PD and parkinsonism, simplifying treatment by giving ZA at home without extra medical visits and BMD testing, and overcoming poor persistence with oral therapies because one infusion may prevent bone loss for at least 2 years. The outcome of this trial will demonstrate how a home-based fracture prevention can reach older PD patients who would not otherwise receive treatment to reduce their high risk of fractures.

Patients with PD will be recruited throughout the US by participating neurologists and health networks as well as the Parkinson's Foundation. Patients may also self-refer to the study. Interested patients can access study information on a study website (topaz.eurekaplatform.org) as well as through the Parkinson's Foundation Helpline. Patients who wish to enroll will be directed to an interactive electronic consent (eConsent). Following eConsent, participants complete a screening questionnaire (to confirm eligibility), followed by a baseline questionnaire. If a participant is determined to be eligible following these steps, they may be scheduled for a Telemedicine assessment to further confirm the PD or parkinsonism diagnosis, unless they have been referred directly from a participating neurologist. If confirmed, the participant will be mailed a supply of vitamin D3 800-1000 IU and instructed to take one vitamin D tablet every day for 2 months. Lastly, a Nurse Home Visit will be scheduled and conducted to confirm final eligibility, randomization, and administration of the study drug, if appropriate. Participants who are randomized will be contacted every 4 months for at least 2 years to determine if they have had any fractures.

• Study Type: Interventional
• Enrollment (Estimated): 2650
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Washington Regional Medical Center
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Berkeley, California, United States, 94705
      • Sutter Health
    • Fountain Valley, California, United States, 92708
      • Parkinson's and Movement Disorder Institute
    • Irvine, California, United States, 92697
      • University of California, Irvine
    • Loma Linda, California, United States, 92350
      • Loma Linda University
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Gatos, California, United States, 95032
      • Valley Parkinson Clinic
    • Palo Alto, California, United States, 94301
      • Parkinson's Disease and Movement Disorder Center of Silicon Valley
    • Riverside, California, United States, 92521
      • University of California, Riverside
    • Sacramento, California, United States, 95816
      • University of California, Davis
    • Sacramento, California, United States, 95816
      • Sutter Health
    • San Francisco, California, United States, 94115
      • University of California, San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado, Denver
    • Grand Junction, Colorado, United States, 81501
      • St. Mary's Medical Center
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut
    • Farmington, Connecticut, United States, 06032
      • University of Connecticut
    • Hartford, Connecticut, United States, 06103
      • Hartford Healthcare
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Miami, Florida, United States, 33146
      • University of Miami
    • Miami, Florida, United States, 33131
      • Parkinson's Foundation
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
    • Atlanta, Georgia, United States, 30310
      • Morehouse School of Medicine
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Queens Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60612
      • Rush University
    • Chicago, Illinois, United States, 60611
      • Northwestern Medicine
    • Chicago, Illinois, United States, 60612
      • Cook County Health & Hospitals System
    • Chicago, Illinois, United States, 60660
      • Loyola University
    • Hines, Illinois, United States, 60141
      • Edward Hines, Jr. VA Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • University Of Kentucky
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • Ochsner Health System
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Boston University
  • Michigan
    • East Lansing, Michigan, United States, 48824
      • Michigan State University
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth-Hitchcock Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • East Setauket, New York, United States, 11733
      • Stony Brook University Medical Center
    • Glen Cove, New York, United States, 11542
      • Northwell Health
    • Great Neck, New York, United States, 11021
      • Northwell Health
    • Manhasset, New York, United States, 11030
      • Northwell Health
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10065
      • Weill Cornell Medicine
    • New York, New York, United States, 10017
      • New York University Langone Health
    • New York, New York, United States, 10019
      • Mount Sinai Beth Israel
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Duke University
    • Winston-Salem, North Carolina, United States, 27109
      • Wake Forest University
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University, UH Cleveland
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15260
      • University of Pittsburgh
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 38157
      • Veracity Neuroscience LLC
    • Nashville, Tennessee, United States, 37240
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Houston Methodist Neurological Institute
    • Houston, Texas, United States, 77030
      • University of Texas Health Houston Medical Center
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Vermont
    • Burlington, Vermont, United States, 05405
      • University of Vermont
  • Washington
    • Kirkland, Washington, United States, 98034
      • Booth Gardner Parkinson's Care Center at EvergreenHealth
  • Wisconsin
    • Madison, Wisconsin, United States, 53706
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women age 60 years or older
• Current Parkinson's Disease diagnosis or neurodegenerative parkinsonism diagnosis (including progressive supranuclear palsy, multiple system atrophy, cortical basal degeneration, vascular parkinsonism, dementia with Lewy bodies or another form of neurodegenerative parkinsonism) based on an expert assessment (neurologist diagnosis via medical records confirmation or Telemedicine Screening Assessment)
• Willing and able to continue in follow-up for at least 2 years
• Willing and able to provide informed consent

Exclusion Criteria:

• History of hip fracture
• Any use of a bisphosphonate drug within the last 12 months
• Use of any other osteoporosis treatment (such as SERMs and denosumab) within the last 6 months
• Tooth extraction or invasive dental procedures within the past 30 days or planned/scheduled extraction/procedure in the next 12 months
• Non-ambulatory, i.e., unable to walk without assistance of another person.
• Undergoing kidney dialysis
• A diagnosis of multiple myeloma or Paget's disease
• Unable to speak or read English sufficiently to complete informed consent
• Any other criteria, which would make the patient unsuitable to participate in this study as determined by the study staff (e.g., an uncontrolled drug and/or alcohol addiction)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Zoledronic acid (ZA); A single intravenous infusion of Zoledronic acid (5 mg) infused over 45 minutes	Drug: Zoledronic Acid 5Mg/Bag 100Ml Inj; Zoledronic acid 5mg/100 ml IV infusion: Zoledronic acid-5 mg (ZA) is an FDA approved therapy for men and postmenopausal women for the treatment and prevention of osteoporosis.; Other Names: Reclast
Placebo Comparator: Placebo; A single intravenous infusion of placebo infused over 45 minutes	Other: Placebo; Normal Saline 100 ml (placebo) IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Clinical Fractures	All clinical fractures	2 years
Number of Participants with Clinical Fractures	All clinical fractures	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Hip Fractures	Hip fractures	2 years
Mortality	All-cause mortality	2 years
Number of Participants Hip Fractures	Hip fractures	5 years
Mortality	All-cause mortality	5 years

Collaborators and Investigators

• Sponsor: California Pacific Medical Center Research Institute
• Collaborators: University of Pittsburgh; Duke University; National Institute on Aging (NIA); University of California, San Francisco; Parkinson's Foundation
• Investigators: Principal Investigator: Steve Cummings, MD, CPMC Research Institute

Publications and helpful links

General Publications

• Tanner CM, Cummings SR, Schwarzschild MA, Brown EG, Dorsey ER, Espay AJ, Galifianakis NB, Goldman SM, Litvan I, Luthra N, McFarland NR, Mitchell KT, Standaert DG, Bauer DC, Greenspan SL, Beck JC, Lyles KW. The TOPAZ study: a home-based trial of zoledronic acid to prevent fractures in neurodegenerative parkinsonism. NPJ Parkinsons Dis. 2021 Mar 1;7(1):16. doi: 10.1038/s41531-021-00162-1.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2019
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: April 2, 2019
• First Submitted That Met QC Criteria: April 18, 2019
• First Posted (Actual): April 23, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 28, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Parkinson's Disease; Bone; Progressive Supranuclear Palsy; Parkinson Disease; Osteoporosis; Multiple System Atrophy; Fracture; Neurology; Zoledronic acid; Dementia with Lewy Bodies; Parkinsonism; Atypical Parkinsonism; Vascular Parkinsonism
• Additional Relevant MeSH Terms: Synucleinopathies; Neurologic Manifestations; Bone Diseases; Musculoskeletal Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mental Disorders; Pathological Conditions, Anatomical; Metabolic Diseases; Neurocognitive Disorders; Eye Diseases; Tauopathies; Neurodegenerative Diseases; Bone Diseases, Metabolic; Movement Disorders; Basal Ganglia Diseases; Cranial Nerve Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Ophthalmoplegia; Ocular Motility Disorders; Paralysis; Hypotension; Osteoporosis; Parkinson Disease; Atrophy; Multiple System Atrophy; Shy-Drager Syndrome; Dementia; Supranuclear Palsy, Progressive; Lewy Body Disease; Parkinsonian Disorders; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: 20180456; 1R01AG059417-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No