Active clinical trials for "Parkinson Disease"

Parkinson's disease (PD) is a neurodegenerative disease characterized by bradykinesia, rigors, and tremor at rest. Distinctive neuropathological signs include progressive loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc) and the presence of immunoreactive protein inclusions for α-syn, Lewy bodies (LB). The clinical phenotype is heterogeneous, both from a motor and non-motor point of view. Furthermore, the prognosis and response to drugs are highly variable and poorly predictable. To date, there are no biomarkers capable of early identification of clinical phenotypes and of predicting response to therapy. This constitutes a serious limit that probably represents one of the causes of the failure of the experimentation of the disease modifying therapies tested up to now (for example the anti-α-sin antibodies). Certainly, a deeper understanding of disease pathogenesis is needed to address these unsolved problems. Oxidative stress and inflammation have critical roles in PD, especially in the prodromal and early stages of PD, as they contribute to pathological progression and also trigger potentially devastating neuroprotective responses, especially in the early stages. Consequently, soluble mediators of these processes may represent potential markers of prodromal phases of the disease. Inflammation is a key factor in the initiation and propagation of a-syn aggregates and the contribution of microglial activation to a-syn pathology has been highlighted recently. Elevated a-syn specific T cell responses may be present years before the diagnosis of motor PD, suggesting a role of neuroinflammation in PD pathogenesis and early diagnosis. Furthermore, studies in rats overexpressing a-syn support the idea that reducing neuroinflammation could improve symptoms in early Parkinson's disease. In particular, drug-targeted anti-inflammatory approaches in a-syn rats prevent central and peripheral inflammation, as well as neuronal dysfunction and motor motor impairment. It is also increasingly evident that panels that combine different biomarkers, with a multimodal approach, are more sensitive and specific, better reflecting the complexity of pathophysiological mechanisms. In fact, the diagnostic sensitivity of some CSF biomarker panels of neurodegeneration in distinguishing between atypical parkinsonisms and Parkinson's disease has been demonstrated. These markers, as well as in the cerebrospinal fluid, can be measured in the serum, albeit with reduced specificity, and in exosomes of central origin, which have recently been described and analyzed also in cohorts of patients with Parkinson's disease. In addition to pharmacological approaches, attention has recently been paid to non-pharmacological therapeutic approaches, such as physical activity. In particular, studies on PD patients show that aerobic exercise improves motor performance by increasing BDNF levels and reducing inflammation. Retrospective studies have found that moderate to vigorous exercise in midlife may protect against PD. In 2018, a phase 2 study investigated the response to treadmill exercise performed at two different intensities (high and moderate) by de novo PD patients, reporting a beneficial effect of moderate treadmill exercise. Although aerobic exercise appears to be the most effective, several studies have used a variety of exercise programs to demonstrate options available for those who cannot physically perform aerobic exercise. In PD patients, physical activity also appears to have beneficial effects on cognition, mood, and sleep quality. Preclinical findings support the hypothesis that physical activity exerts its beneficial effect by increasing levels of BDNF and anti-inflammatory cytokines and inhibiting pro-inflammatory factors. In this study the investigators will measure changes in clinical scales and biomarkers in patients who undergo either an intensive physical activity protocol or continue their routine sedentary life.

Study comparing pain intensity and discomfort in patients with Parkinson´s disease and healthy controls during inducement of mechanical, thermal, and chemical experimental pain

This project will provide preliminary data on the feasibility and effects of exercise and VR on motor behavior and neuroplasticity in PD. Results from this work will provide insight into whether combination interventions utilizing AE and VR have parallel effects on cognition, gait, and neuroplasticity in PD.

The study is a pilot study on Parkinson's disease patients to evaluate Combined deep brain stimulation of the substantia nigra pars reticulata and of the subthalamic nucleus for unresponsive freezing of gait.

The aim of this protocol is to evaluate the effects of a home-based therapeutic exercise program applied in patients with PD or secondary parkinsonism to reverse frailty. The design of this study is experimental, prospective, randomized and double blind. The study population that will be part of this study will be men and women with a diagnosis of PD or secondary parkinsonism belonging to the Health Area V of the Health Service of the Principality of Asturias, Spain.

Patients with Parkinson's disease (PD) are commonly treated with a combination of levodopa and a decarboxylase inhibitor (DCI). However, many PD patients experience motor fluctuations (OFF episodes), even with their regular levodopa/DCI treatment. This unmet medical need was addressed by the approval of INBRIJA®, an orally inhaled product, for producing therapeutic relief during the OFF episodes. INBRIJA® is a capsule-based inhaler system and in order to administer the full dose of levodopa, the patients need to inhale the contents of two capsules. In order to administer the full dose of levodopa, patients need to inhale the contents of two capsules. Since the INBRIJA® device is a standalone and reusable unit, the patients have to load the capsule prior to inhalation several times a day during the OFF episodes (except early-morning OFF) to get relief. Also, the INBRIJA® device is repeatedly used by PD patients and therefore needs to be properly cleaned to avoid contamination. PureIMS is developing a more user-friendly alternative called Levodopa Cyclops™, a pre-filled drug-device combination of levodopa inhalation powder for use with the Cyclops™ dry powder inhaler. Due to the nature of the Cyclops™, it offers PD patients greater ease and convenience in use. Moreover, the device's moderate to high resistance to airflow and minimal use of excipients suggests minimal cough episodes during oral inhalation. The current study is planned in order to determine the dose at which comparative bioavailability of Levodopa Cyclops™ will be reached compared to INBRIJA®.

The present multicenter, randomized, double-blind, placebo-controlled clinical trial will investigate whether the prolonged administration of high-dose oral Ambroxol over 52 weeks is safe, tolerable, able to change Glucocerebrosidase enzyme activity and alpha-synuclein levels in the central nervous system and, ultimately, to reduce the progression of cognitive decline and motor disability in 60 individuals with Parkinson's disease with mutations of the glucocerebrosidase gene (GBA1; OMIM 606463). Participants will undergo clinical, biomarker blood and cerebrospinal fluid analysis, neuropsychological, neuroimaging assessment throughout the course of the study.

This is a multi-center, international, open-label, safety study of ND0612, a solution of levodopa/carbidopa (LD/CD) delivered via a pump system as a continuous SC infusion in subjects with advanced Parkinson's Disease (PD).

To determine the efficacy of frameless Virtual Cone Radiosurgical Thalamotomy for medically refractory tremor resulting from either Essential Tremor or Tremor-Dominant Parkinson's Disease with the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) in patients who are not candidates for deep brain stimulation (DBS).

The proposed study is to evaluate the effectiveness of ExAblate Transcranial MRgFUS as a tool for creating a unilateral lesion in the Vim thalamus or the globus pallidus (GPi) in patients with treatment-refractory symptoms of movement disorders.