Clinical trial NCT03924414: Trial of Parkinson's And Zoledronic Acid
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Parkinson Disease
Osteoporosis
Parkinsonism
Parkinson's Disease and Parkinsonism
Atypical Parkinsonism
Progressive Supranuclear Palsy
Multiple System Atrophy
Vascular Parkinsonism
Dementia With Lewy Bodies
Keywords: Parkinson Disease
Parkinson's Disease
Osteoporosis
Zoledronic acid
Neurology
Bone
Fracture
Parkinsonism
Atypical Parkinsonism
Progressive Supranuclear Palsy
Multiple System Atrophy
Vascular Parkinsonism
Dementia with Lewy Bodies
Lead sponsor: California Pacific Medical Center Research Institute
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: University of California, San Francisco
name: Duke University
name: University of Pittsburgh
name: Parkinson's Foundation
First posted: 2019-04-23
Enrollment: 2650
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This 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 or parkinsonism with at least 2 years of follow-up.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Participants with Clinical Fractures
timeFrame: 2 years
measure: Number of Participants with Clinical Fractures
timeFrame: 5 years
Secondary outcomes:
measure: Number of Participants Hip Fractures
timeFrame: 2 years
measure: Number of Participants Hip Fractures
timeFrame: 5 years
measure: Mortality
timeFrame: 2 years
measure: Mortality
timeFrame: 5 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Fayetteville
country: United States
facility: Washington Regional Medical Center
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Berkeley
country: United States
facility: Sutter Health
state: California
city: Fountain Valley
country: United States
facility: Parkinson's and Movement Disorder Institute
state: California
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Los Gatos
country: United States
facility: Valley Parkinson Clinic
state: California
city: Palo Alto
country: United States
facility: Parkinson's Disease and Movement Disorder Center of Silicon Valley
state: California
city: Riverside
country: United States
facility: University of California, Riverside
state: California
city: Sacramento
country: United States
facility: Sutter Health
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado, Denver
state: Colorado
city: Grand Junction
country: United States
facility: St. Mary&#39;s Medical Center
state: Colorado
city: Farmington
country: United States
facility: University of Connecticut
state: Connecticut
city: Farmington
country: United States
facility: University of Connecticut
state: Connecticut
city: Hartford
country: United States
facility: Hartford Healthcare
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: Parkinson's Foundation
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Morehouse School of Medicine
state: Georgia
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Honolulu
country: United States
facility: Queens Medical Center
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Medicine
state: Illinois
city: Chicago
country: United States
facility: Cook County Health & Hospitals System
state: Illinois
city: Chicago
country: United States
facility: Rush University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Chicago
country: United States
facility: Loyola University
state: Illinois
city: Hines
country: United States
facility: Edward Hines, Jr. VA Hospital
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Health System
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: East Setauket
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Glen Cove
country: United States
facility: Northwell Health
state: New York
city: Great Neck
country: United States
facility: Northwell Health
state: New York
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: New York University Langone Health
state: New York
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University, UH Cleveland
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: Veracity Neuroscience LLC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Neurological Institute
state: Texas
city: Houston
country: United States
facility: University of Texas Health Houston Medical Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Kirkland
country: United States
facility: Booth Gardner Parkinson's Care Center at EvergreenHealth
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: CPMC Research Institute
name: Steve Cummings, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.