Trial Summary
What is the purpose of this trial?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.
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.
Is the drug Zoledronic Acid a promising treatment for Parkinson's Disease?The information provided does not mention Zoledronic Acid as a treatment for Parkinson's Disease. Instead, it focuses on Zonisamide, which is shown to improve motor function in Parkinson's patients. Therefore, there is no evidence here to suggest that Zoledronic Acid is a promising treatment for Parkinson's Disease.567910
What data supports the idea that Zoledronic Acid for Parkinson's Disease is an effective drug?The available research does not provide any data supporting the effectiveness of Zoledronic Acid for treating Parkinson's Disease. The studies focus on other treatments and conditions related to Parkinson's, such as surgical interventions and joint replacements, but do not mention Zoledronic Acid as a treatment for Parkinson's Disease.2341214
What safety data exists for Zoledronic Acid in treating Parkinson's Disease?The provided research does not contain specific safety data for Zoledronic Acid (also known as Zometa or Reclast) in the treatment of Parkinson's Disease. The studies focus on other drugs like istradefylline, safinamide, and zonisamide for Parkinson's Disease, but none mention Zoledronic Acid. Therefore, no relevant safety data for Zoledronic Acid in this context is available from the provided research.18111315
Eligibility Criteria
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.
I have been diagnosed with Parkinson's Disease or a similar condition by a specialist.
I have been diagnosed with Parkinson's Disease or a similar condition by a neurologist.
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.
I am currently receiving kidney dialysis.
I have been diagnosed with multiple myeloma or Paget's disease.
I haven't taken any osteoporosis treatments in the last 6 months.
I have had a hip fracture in the past.
Treatment Details
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.
2Treatment groups
Active Control
Placebo Group
Group I: Zoledronic acid (ZA)Active Control1 Intervention
A single intravenous infusion of Zoledronic acid (5 mg) infused over 45 minutes
Group II: PlaceboPlacebo Group1 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
Cedars-Sinai Medical CenterLos Angeles, CA
St. Mary's Medical CenterGrand Junction, CO
Hartford HealthcareHartford, CT
Morehouse School of MedicineAtlanta, GA
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Who is running the clinical trial?
California Pacific Medical Center Research InstituteLead Sponsor
National Institute on Aging (NIA)Collaborator
University of California, San FranciscoCollaborator
Duke UniversityCollaborator
University of PittsburghCollaborator
Parkinson's FoundationCollaborator
References
[Drug-induced extrapyramidal disorders]. [2022]We analyze 402 drug-adverse events consisting of movement disorders or aggravation of parkinsonisms, submitted to Sistema Español de Farmacovigilancia until 1994. Our aim is to know patient characteristics and the drugs related with these submissions. Most of them (64) belong to calcium-entry blocker group (31%) and benzamides (27%). Case age intervals more frequent were 11-30 and 60-80 years-old and the events affect predominantly females. The percentage of serious adverse events were near 80%. We think that drug-related parkinsonisms have high prevalence rate and that the role of calcium-entry blockers in these events should be considered at the moment to prescribe groups.
[Neurosurgical stereotactic treatment in Parkinson's disease]. [2017]For patients with Parkinson's disease who have become unresponsive to pharmacotherapy or have developed severe motor complications due to medical therapy, a number of symptomatic neurosurgical interventions are available: thalamotomy, thalamic stimulation and pallidotomy. These stereotactic operations are performed under local anaesthesia. The target is located using anatomical and physiological techniques, after which the neuro-ablative or neuromodulatory procedure is performed. The choice of the target depends on the symptoms of the patient that most impair daily functioning. In case of dominating tremor, thalamic surgery is performed. Patients who are mainly incapacitated by rigidity, hypokinesia or pharmacotherapy-induced dyskinesias are suitable candidates for pallidotomy. Contraindications are cognitive dysfunction, severe disturbance of gait and balance, advanced cerebral atrophy on CT or MRI, limited life expectancy and a poor general condition enhancing surgical risk, e.g. coagulation disorders or uncontrolled hypertension. Surgical treatment of Parkinson's disease is being carried out in clinical trials in the Netherlands in the Academic Medical Centre in Amsterdam, the Academic Hospital in Groningen and the St. Elisabeth Hospital in Tilburg.
[Gait in patients with Parkinson's disease after surgically treated hip fracture]. [2014]The aims of this study were: 1) to evaluate the degree of walking of patients with Parkinson s syndrome after hip fracture surgically treated; 2) to reexamine the evidence for internal fixation versus endoprosthesis.
Parkinson's disease patients who fracture their neck of femur: a review of outcome data. [2008]Parkinson's disease patients are at increased risk of falls and osteoporosis. They present a challenge to those who treat them for fracture neck of femur. There are conflicting views as to whether they have a worse prognosis, compared to age matched controls. This review discusses their care, including surgical approach and technique, to post-operative management and complications. It highlights the limitations in evidence and the need for further research.
Zonisamide: in Parkinson's disease. [2021]Zonisamide, a widely available antiepileptic drug, has been approved in Japan as adjunctive therapy with levodopa for the treatment of previously treated patients with Parkinson's disease. It is an oral 1,2-benzisoxazole-3-methanesulfonamide and is associated with increased striatal dopamine levels in animal models. In two 12-week, randomized, double-blind, multicentre trials in adult patients with inadequately controlled Parkinson's disease and receiving levodopa, zonisamide 25 mg once daily (the recommended dosage) significantly improved motor function from baseline at final assessment, as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) Part III total score (primary endpoint), compared with placebo. Zonisamide 25 mg once daily as adjunctive therapy with levodopa was generally well tolerated by patients with Parkinson's disease. The overall incidence of adverse events was not significantly different between zonisamide 25 mg once daily and placebo groups in the phase IIb/III trial.
[The discovery of an antiparkinsonian drug, zonisamide]. [2019]We serendipitously found that zonisamide (ZNS), an antiepileptic agent, has beneficial effects on Parkinson disease. A 25 mg once a day of ZNS (200-600 mg/day for epilepsy), significantly improves motor function of advanced patients with Parkinson disease. Its effects maintained at least one year even in patients with advanced stage. It was finally approved as an anti parkinsonian agent in Japan on January 2009. As the mechanism of antiparkinsonian effects of ZNS, we showed that ZNS increases dopamine contents in the striatum by activating dopamine synthesis through increasing the levels of tyrosine hydroxylase (TH) mRNA and TH protein. It moderately inhibits monoamine oxydase (MAO) activity. ZNS shows significant inhibition on T-type Ca++ channel. It may also affect the beneficial effects of ZNS on Parkinson disease. ZNS also showed neuroprotective effects on several parkinsonian models. It markedly inhibited quinoprotein formation and increased the level of glutathione by enhancing the astroglial cystine transport system and/or astroglial proliferation through S100beta. We will verify the neuroprotective effects of ZNS on patients with Parkinson disease and study the factors responsible for the individual difference of the effects of ZNS by using genome wide association study (GWAS) in the near feature.
Upcoming treatments in Parkinson's disease, including gene therapy. [2012]Progress is being made in the development of three categories of therapy for Parkinson's disease: (1) Symptomatic, (2) Neuroprotective, (3) Neurorestorative. Evolving approaches to symptomatic therapy, already in clinical trials, include the use of adenosine 2(A) antagonists, novel glutamate antagonists, and serotonin receptor antagonists, the latter for the therapy of Parkinson's psychosis and/or levodopa-induced dyskinesias. Examples of promising neuroprotective therapies under evaluation include the administration of creatine, urate-inducing compounds, calcium channel blockers, and pioglitazone, a peroxisome proliferator-activated receptor agonist. Cell-based restorative therapies are not the subject of this presentation, but various forms of gene therapy have shown promise in human Parkinson's disease trials. These protocols typically involve gene transfer into the CNS through the use of viral vectors. Currently, the most advanced studies of this technique involve delivery of an adeno-associated viral vector encoding glutamic acid decarboxylase into the subthalamic nucleus. This treatment has shown modest benefit in early clinical trials. Other gene therapies, in various stages of human clinical trials, include gene transfer for the production of trophic factors, for aromatic amino acid decarboxylase alone, and most recently, a lentiviral vector transfer of an enzymatic dopamine "factory" consisting of three essential enzymes required for production for this neurotransmitter.
Istradefylline, an adenosine A₂A receptor antagonist, for patients with Parkinson's Disease: a meta-analysis. [2014]To assess the efficacy and safety of istradefylline as an adjunct to levodopa in patients with Parkinson's Disease (PD).
Zonisamide Enhances Motor Effects of Levodopa, Not of Apomorphine, in a Rat Model of Parkinson's Disease. [2020]Zonisamide is a relatively recent drug for Parkinson's disease. Multiple hypotheses have been proposed to explain the antiparkinsonian effects of zonisamide. However, it is still unclear whether the effect of zonisamide is mainly due to dopaminergic modification in the striatum, or if zonisamide works through nondopaminergic pathways. We conducted the present study to determine the mechanism that is mainly responsible for zonisamide's effects in Parkinson's disease. We examined the effects of zonisamide on motor symptoms in a hemiparkinsonian rat model when administered singly, coadministered with levodopa, a dopamine precursor, or apomorphine, a D1 and D2 dopamine receptor agonist. We used 6-hydroxydopamine-lesioned hemiparkinsonian rats, which were allocated to one of five groups: 14 rats received levodopa only (6 mg/kg), 12 rats received levodopa (6 mg/kg) plus zonisamide (50 mg/kg), six rats received apomorphine only (0.05 mg/kg), six rats received apomorphine (0.05 mg/kg) plus zonisamide (50 mg/kg), and six rats received zonisamide only (50 mg/kg). The drugs were administered once daily for 15 days. We evaluated abnormal involuntary movement every 20 min during a 3 h period following the injection of drugs on treatment Days 1, 8, and 15. Western blot analyses for dopamine decarboxylase and vesicular monoamine transferase-2 were performed using striatal tissues in the lesioned side of rats in the levodopa only group (n = 6) and levodopa plus zonisamide group (n = 4). Levodopa-induced abnormal involuntary movement was significantly enhanced by coadministration of zonisamide. In contrast, zonisamide had no effect on apomorphine-induced abnormal involuntary movement. Zonisamide monotherapy did not induce abnormal involuntary movement. Zonisamide did not affect striatal expression of dopamine decarboxylase or vesicular monoamine transferase-2. In conclusion, zonisamide appears to generate its antiparkinsonian effects by modulating levodopa-dopamine metabolism in the parkinsonian striatum.
Effect of zonisamide on parkinsonism in patients with dementia with Lewy bodies: A phase 3 randomized clinical trial. [2021]Zonisamide is approved in Japan for treating motor dysfunction in Parkinson's disease, and might also be effective for parkinsonism in patients with dementia with Lewy bodies (DLB). Our study evaluated the safety and efficacy of zonisamide for treating parkinsonism in patients with DLB.
A systematic review and meta-analysis of safety and efficacy of safinamide for motor fluctuations in patients with Parkinson's disease. [2020]Background: Safinamide, a recently developed drug with several mechanisms of action has been investigated as an add-on therapy for Parkinson's disease patients suffering from motor complications due to the usage of anti-Parkinson's medications such as levodopa and dopaminergic drugs. The aim of the study is to investigate the efficacy and safety of Safinamide as add-on therapy for Parkinson's disease patients.   Methods: A computerized literature search was conducted of PubMed, EMBASE, ClinicalTrial.gov and Cochrane Library until August 2019. We selected relevant randomized controlled trials comparing safinamide groups to placebo groups. Relevant outcomes were pooled as mean difference (MD) and risk ratio (RR) using Review Manager 5.3. Results: We found that the overall MD of changes in "off-time" and "on time without troublesome dyskinesia" favored the safinamide group over the placebo group (MD -0.72 h, 95% CI -0.89 to -0.56 and MD 0.71 h, 95% CI 0.52 to 0.90, respectively). Additionally, the overall MD of change in Unified Parkinson's Disease Rating Scale part three (UPDRS III) favored the safinamide group (MD -1.83, 95% CI -2.43 to -1.23). In case of adverse events, the pooled meta-analysis did not favor the safinamide group over the placebo group. Conclusions: In this study, we provide class I evidence about the potential role of safinamide as an add-on therapy for Parkinson's disease patients suffering from motor fluctuations. However, a few included studies did not mention the data of important outcomes. Also, we report high risk of bias in individual studies. Future randomized controlled trials with different doses are recommended to provide more evidence for the efficacy and safety of safinamide as a treatment for motor complications of anti-Parkinson's medications.
Unicompartmental knee arthroplasty in patients with Parkinson's disease. [2021]Parkinson's disease (PD) adversely affects physical function after joint replacement. The biomechanical advantages of unicompartmental knee arthroplasty (UKA) may be particularly beneficial for these patients who suffer from gait and kinetic abnormalities. We aimed to describe the functional outcomes, complications and survivorship after UKA in patients with PD.
Zonisamide's Efficacy and Safety on Parkinson's Disease and Dementia with Lewy Bodies: A Meta-Analysis and Systematic Review. [2022]Clinical data has recently shown an association between Parkinson's disease (PD), Dementia with Lewy bodies (DLB), and zonisamide. The purpose of this study was to thoroughly evaluate the efficacy and safety of zonisamide in PD and DLB.
Botulinum Toxin as an Adjunctive Therapy for Immobilization of a Distal Humerus Fracture in Parkinson's Disease-Associated Psychosis: A Case Report. [2023]BACKGROUND Attainment of extremity immobilization in orthopedic trauma patients experiencing psychosis is often uniquely challenging. Many fractures, including those of the distal humerus, require a period of immobilization postoperatively to optimize fracture healing. Patients with Parkinson's disease have also been shown to have lower rates of union after fracture compared to the general population. The combination of Parkinson's disease and associated psychosis requires heightened attention to those parameters that may hinder fracture healing, such as inadequate immobilization of the fracture. Botulinum toxin has previously been described as a potential adjunctive therapy for fracture immobilization but has not yet been described in the setting of distal humerus fractures. CASE REPORT A 75-year-old woman with Parkinson's disease-associated psychosis presented 2 weeks after open reduction and internal fixation of a distal third humeral shaft fracture due to failure of fixation and episodes of violent hallucinations. The patient underwent irrigation and debridement, and revision open reduction and internal fixation. Given her uncontrolled hallucinations, intramuscular botulinum toxin injections were given to the right triceps, biceps, and brachialis muscles to aid in the immobilization of the right extremity and protect the surgical site during the perioperative period. The patient subsequently followed up at the clinic 3 months postoperatively with ongoing fracture healing, evidenced by bridging callous and bone formation on radiographs, as well as a return of motion to the extremity. CONCLUSIONS Botulinum toxin may be a safe and effective adjunct for fracture immobilization in patients who are difficult to immobilize and have high fixation failure risk.
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. [2023]Parkinson's Disease (PD) is a progressive age-related neurodegenerative condition requiring new therapeutic alternatives. Safinamide, a novel levodopa add-on therapy, positively affects disease fluctuations by modulating both dopaminergic and glutamatergic systems. To further investigate the use of safinamide in European routine clinical practice, the present post-hoc analysis aimed to understand safinamide's safety profile within the Spanish study population.