Trial of Parkinson's And Zoledronic Acid

Study Overview
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Brief Summary
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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 3500 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
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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.

Official Title
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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

Conditions
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Vascular Parkinsonism, Parkinson Disease, Osteoporosis, Parkinsonism, Parkinson's Disease and Parkinsonism, Atypical Parkinsonism, Progressive Supranuclear Palsy, Multiple System Atrophy, Dementia With Lewy Bodies

Intervention / Treatment
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* Drug: Zoledronic Acid 5Mg/Bag 100Ml Inj
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Zoledronic acid (ZA)<br>A single intravenous infusion of Zoledronic acid (5 mg) infused over 45 minutes | Drug: Zoledronic Acid 5Mg/Bag 100Ml Inj<br>* 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.<br>* Other names: Reclast;|
| Placebo Comparator: Placebo<br>A single intravenous infusion of placebo infused over 45 minutes | Other: Placebo<br>* Normal Saline 100 ml (placebo) IV infusion<br>|

What is the study measuring?
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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 | 
| Number of Participants Hip Fractures | Hip fractures | 5 years | 
| Mortality | All-cause mortality | 2 years | 
| Mortality | All-cause mortality | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Progressive Supranuclear Palsy, Multiple System Atrophy, Vascular Parkinsonism, Dementia with Lewy Bodies, Parkinson Disease, Parkinson's Disease, Osteoporosis, Zoledronic acid, Neurology, Bone, Fracture, Parkinsonism, Atypical Parkinsonism