Zoledronic Acid for Parkinson's Disease

(TOPAZ Trial)

Not currently recruiting at 75 trial locations

Overseen By Salima Brillman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: California Pacific Medical Center Research Institute

Must not be taking: Bisphosphonates, SERMs, Denosumab

Disqualifiers: Hip fracture, Non-ambulatory, Kidney dialysis, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a single infusion of zoledronic acid, a medication used to strengthen bones, can prevent fractures in people with Parkinson's disease. It compares the drug's effects against a placebo (a substance with no active treatment) to determine which is more effective. The study seeks participants aged 60 or older who have been diagnosed with Parkinson's or similar conditions, have not had a hip fracture, and have not recently used specific bone-related treatments. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have used bisphosphonate drugs in the last 12 months or other osteoporosis treatments in the last 6 months.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used bisphosphonate drugs in the last 12 months or other osteoporosis treatments in the last 6 months.

What is the safety track record for Zoledronic Acid?

Research shows that zoledronic acid is generally safe for people. Studies have found that it can lower the risk of various bone fractures. For example, one study found it reduced non-spinal fractures by 25% and other types of fractures by 33%. It also reduced spinal fractures by 77%.

While zoledronic acid is usually safe, some people report mild side effects. These can include flu-like symptoms, such as fever and muscle aches, after treatment. These effects typically resolve on their own. It's important to know that the FDA has already approved this treatment for other uses, which supports its safety.

In summary, zoledronic acid has been safely used for other conditions, and current research suggests it is well-tolerated. However, like any medication, it can have side effects, so discussing any concerns with a healthcare provider is always a good idea. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for Parkinson's disease, which mostly focus on managing dopamine levels and symptoms, Zoledronic acid represents a novel approach. Researchers are excited about Zoledronic acid because it is traditionally used to treat bone-related conditions and now shows promise in potentially affecting the progression of Parkinson's by altering the disease's underlying mechanisms. This treatment is distinct due to its unique delivery method as a single intravenous infusion, which may offer convenience compared to daily oral medications. By targeting pathways that are not addressed by typical Parkinson's therapies, Zoledronic acid could open new avenues for managing the disease.

What evidence suggests that zoledronic acid might be an effective treatment for preventing fractures in Parkinson's disease?

Research has shown that zoledronic acid can help prevent broken bones, particularly in individuals with conditions like Parkinson's disease. People with Parkinson's are more prone to falls and fractures. Zoledronic acid strengthens bones and reduces fracture risk. In past studies, patients who took zoledronic acid experienced fewer fractures than those who did not. This trial will compare a single intravenous infusion of zoledronic acid to a placebo to assess its effectiveness in preventing fractures in people with Parkinson's disease. Already approved for other uses, this treatment has demonstrated its ability to strengthen bones, offering hope that it might also prevent fractures in those with Parkinson's disease. ^{1 2 4 5 6}

Who Is on the Research Team?

Steve Cummings, MD

Principal Investigator

CPMC Research Institute

Are You a Good Fit for This Trial?

This trial is for men and women aged 60 or older with Parkinson's disease or parkinsonism, who can follow the study for at least 2 years. They must be able to consent and have a neurologist-confirmed diagnosis. People using bisphosphonates in the last year, those with recent or planned dental procedures, on osteoporosis treatments within 6 months, undergoing dialysis, non-ambulatory individuals, or with certain other diseases are excluded.

Inclusion Criteria

I am 60 years old or older.

I have been diagnosed with Parkinson's Disease or parkinsonism by a neurologist.

Willing and able to continue in follow-up for at least 2 years

Exclusion Criteria

I need someone's help to walk.

I haven't had nor plan to have any tooth extractions or major dental work soon.

The study staff decides that you are not suitable for the study, for example, if you have an uncontrolled drug or alcohol addiction.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

eConsent, screening questionnaire, baseline questionnaire, Telemedicine assessment, Nurse Home Visit

Treatment

Participants receive a single intravenous infusion of Zoledronic acid (5 mg) or placebo

1 day

1 Nurse Home Visit for drug administration

Follow-up

Participants are monitored for fractures and mortality every 4 months

2 years

Contact every 4 months

Long-term follow-up

Participants are monitored for clinical and hip fractures

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Zoledronic Acid

Trial Overview

The study tests if a single infusion of Zoledronic Acid (ZA) can prevent fractures compared to a placebo in patients with Parkinson's-related conditions. It's randomized and blinded—meaning neither participants nor researchers know who gets ZA or placebo—and involves over three thousand participants across the U.S.

How Is the Trial Designed?

Group I: Zoledronic acid (ZA) Active Control 1 Intervention

A single intravenous infusion of Zoledronic acid (5 mg) infused over 45 minutes

Group II: Placebo Placebo Group 1 Intervention

A single intravenous infusion of placebo infused over 45 minutes

Zoledronic Acid is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Zometa for:

• Prevention of skeletal events in patients with bone metastases from solid tumors
• Treatment of tumor-induced hypercalcemia

Approved in United States as Reclast for:

• Treatment and prevention of osteoporosis in postmenopausal women
• Treatment and prevention of glucocorticoid-induced osteoporosis
• Treatment of Paget's disease of bone

Approved in Canada as Zometa for:

• Prevention of skeletal events in patients with bone metastases from solid tumors
• Treatment of tumor-induced hypercalcemia
• Treatment of osteoporosis in postmenopausal women

Approved in Japan as Zometa for:

• Treatment of bone metastases from solid tumors
• Treatment of tumor-induced hypercalcemia
• Treatment of osteoporosis

Who Is Running the Clinical Trial?

California Pacific Medical Center Research Institute

Lead Sponsor

Trials

44

Recruited

10,600+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

Parkinson's Foundation

Collaborator

Trials

13

Recruited

1,030,000+

Published Research Related to This Trial

In two 12-week clinical trials involving adult patients with Parkinson's disease, zonisamide (25 mg once daily) significantly improved motor function compared to placebo, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) Part III.

Zonisamide was generally well tolerated, with no significant difference in the incidence of adverse events between the zonisamide and placebo groups, indicating a favorable safety profile as an adjunctive therapy with levodopa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zonisamide: in Parkinson's disease. Yang, LP., Perry, CM.[2021]

Current research is advancing in three main therapy categories for Parkinson's disease: symptomatic treatments, neuroprotective strategies, and neurorestorative approaches, with several promising therapies in clinical trials.

Gene therapy techniques, particularly those using viral vectors to deliver therapeutic genes into the brain, have shown modest benefits in early trials, including a method that encodes for glutamic acid decarboxylase, which may help improve symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upcoming treatments in Parkinson's disease, including gene therapy. Rodnitzky, RL.[2012]

Zonisamide (ZNS) has been found to significantly improve motor function in advanced Parkinson's disease patients at a low dose of 25 mg per day, with effects lasting for at least one year, leading to its approval as an anti-parkinsonian agent in Japan in 2009.

The mechanism of ZNS's benefits includes increasing dopamine levels in the brain by enhancing the synthesis of dopamine and inhibiting monoamine oxidase activity, along with neuroprotective effects that may help in managing Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The discovery of an antiparkinsonian drug, zonisamide]. Murata, M.[2019]

Zonisamide enhances the effects of levodopa in treating motor symptoms of Parkinson's disease, but it also increases levodopa-induced abnormal involuntary movements, indicating a complex interaction between the two drugs.

The study suggests that zonisamide's antiparkinsonian effects are primarily due to its modulation of levodopa-dopamine metabolism in the striatum, rather than through direct dopaminergic pathways, as it did not affect key dopamine-related proteins in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zonisamide Enhances Motor Effects of Levodopa, Not of Apomorphine, in a Rat Model of Parkinson's Disease. Nishijima, H., Miki, Y., Ueno, S., et al.[2020]

In a phase 3 trial involving 351 patients with dementia with Lewy bodies (DLB), zonisamide significantly improved motor function compared to placebo, with a notable reduction in the Unified Parkinson's Disease Rating Scale (UPDRS) scores at 12 weeks.

Both 25 mg and 50 mg doses of zonisamide were found to be safe and well tolerated, with adverse events occurring in about 47% to 55% of patients, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of zonisamide on parkinsonism in patients with dementia with Lewy bodies: A phase 3 randomized clinical trial. Murata, M., Odawara, T., Hasegawa, K., et al.[2021]

In a study of 10 patients with Parkinson's disease undergoing unicompartmental knee arthroplasty (UKA), there were no perioperative complications, and patients experienced significant improvements in knee pain and physical function as measured by the Knee Society Scores and SF-36 Physical Component Scores.

Despite the improvements in pain and some functional scores, the surgery did not lead to better range of motion or overall knee function, as many patients still had unchanged flexion contractures and only a few were able to ambulate independently at follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unicompartmental knee arthroplasty in patients with Parkinson's disease. Goh, GS., Zeng, GJ., Thever, Y., et al.[2021]

Parkinson's disease patients face higher risks of falls and osteoporosis, complicating their treatment for hip fractures, particularly regarding surgical approaches and post-operative care.

There is uncertainty about whether Parkinson's patients have a worse prognosis after hip fractures compared to age-matched individuals, indicating a need for more research to clarify their outcomes and improve care strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parkinson's disease patients who fracture their neck of femur: a review of outcome data. Clubb, VJ., Clubb, SE., Buckley, S.[2008]

In a study of 41 patients with Parkinson's syndrome who underwent hip fracture surgery, those treated with endoprosthesis showed significantly better walking recovery compared to those treated with internal fixation, with 62.5% of endoprosthesis patients able to walk independently after rehabilitation.

Overall, Parkinson's disease negatively impacts walking recovery after hip fractures, as 21.9% of patients were unable to walk at the end of rehabilitation, highlighting the challenges faced by this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Gait in patients with Parkinson's disease after surgically treated hip fracture]. Gialanella, B.[2014]

In a study of 511 Spanish patients with Parkinson's Disease, safinamide demonstrated a favorable safety profile and led to significant improvements in motor function, with 57.4% of patients showing clinically meaningful benefits when used as an add-on to levodopa.

Motor complications decreased from 83.2% to 63.3% over the study period, indicating safinamide's efficacy in managing symptoms, although caution is advised for patients with cognitive impairment due to a slightly higher frequency of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SYNAPSES. A European observational study to evaluate the safety and the effectiveness of safinamide in routine clinical practice: post-hoc analysis of the Spanish study population. Kulisevsky, J., Esquivel, A., Freire-Álvarez, E., et al.[2023]

Zonisamide significantly improves motor function in patients with Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), as evidenced by a reduction in the UPDRS III total score in a study of 1749 patients.

While zonisamide shows promise as a treatment option, it may increase the risk of adverse effects such as contusions and reduced appetite in DLB patients, and somnolence in PD patients, indicating the need for further safety evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zonisamide's Efficacy and Safety on Parkinson's Disease and Dementia with Lewy Bodies: A Meta-Analysis and Systematic Review. Kong, L., Xi, J., Jiang, Z., et al.[2022]

Safinamide, when used as an add-on therapy for Parkinson's disease, significantly reduces 'off-time' and increases 'on time without troublesome dyskinesia', showing its efficacy in managing motor complications associated with anti-Parkinson's medications.

The study found no significant difference in adverse events between the safinamide and placebo groups, suggesting that safinamide is a safe option for patients, although further research is needed due to some studies having a high risk of bias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of safety and efficacy of safinamide for motor fluctuations in patients with Parkinson's disease. Abdelalem Aziz Ahmed, M.[2020]

COMT inhibitors have been shown to effectively prolong the action of levodopa in Parkinson's disease patients experiencing the 'wearing off' phenomenon, providing a new treatment option for those with fluctuating responses to standard therapy.

Clozapine not only alleviates levodopa-induced psychosis but also helps reduce tremors and dyskinesias, highlighting its dual role in managing symptoms of Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New medical and surgical treatments for Parkinson's disease. Klockgether, T., Löschmann, PA., Wüllner, U.[2019]

Surgical interventions like thalamotomy, thalamic stimulation, and pallidotomy can be effective for Parkinson's disease patients who do not respond to medication or have severe motor complications, with the choice of procedure tailored to the patient's specific symptoms.

These surgeries are performed under local anesthesia and involve precise targeting based on anatomical and physiological techniques, but are contraindicated in patients with cognitive dysfunction, severe gait issues, or other health risks that could complicate surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Neurosurgical stereotactic treatment in Parkinson's disease]. Schuurman, PR., Speelman, JD., de Bie, RM., et al.[2017]

In a case study of a 75-year-old woman with Parkinson's disease and psychosis, intramuscular botulinum toxin injections were successfully used to aid in the immobilization of her fractured arm after surgery, helping to protect the surgical site during recovery.

Three months post-surgery, the patient showed signs of successful fracture healing, indicating that botulinum toxin could be a safe and effective option for patients who struggle with immobilization due to psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum Toxin as an Adjunctive Therapy for Immobilization of a Distal Humerus Fracture in Parkinson's Disease-Associated Psychosis: A Case Report. Lapow, J., Hirth, J., Agarwalla, A., et al.[2023]

A review of 402 drug-related adverse events linked to movement disorders revealed that calcium-entry blockers (31%) and benzamides (27%) were the most commonly implicated drugs.

The study found that serious adverse events occurred in nearly 80% of cases, predominantly affecting females and individuals aged 11-30 and 60-80 years, highlighting the need for caution when prescribing these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug-induced extrapyramidal disorders]. Horga, JF., Navarro, M., Peiró, V., et al.[2022]

Istradefylline, when used alongside levodopa, significantly reduces the time patients with Parkinson's Disease spend in the OFF state and improves motor function as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) Part III.

The study found that istradefylline is safe, with no significant differences in adverse events compared to placebo, although it was associated with a higher risk of dyskinesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Istradefylline, an adenosine A₂A receptor antagonist, for patients with Parkinson's Disease: a meta-analysis. Chen, W., Wang, H., Wei, H., et al.[2014]

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An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

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Management of Osteoporosis in Parkinson's Disease

The efficacy of zoledronic acid in PwP is currently being assessed in the ongoing Trial of Parkinson's And Zoledronic Acid. Denosumab, a human ...

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Nonvertebral fractures, clinical fractures, and clinical vertebral fractures were reduced by 25%, 33%, and 77%, respectively (P<0.001 for all ...