Parkinson Disease (PD)

Administering transcutaneous vagus nerve stimulation in patients with Parkinson's disease to see how it affects stomach and brain activity.

The goal of this clinical trial is to learn if a tailored amino acid supplement works to help adults living with Parkinson's disease to improve nutrition, metabolic function, body composition, and physical and mental function. The main questions it aims to answer are: Does the tailored amino acid supplement increase essential amino acids (nutritional status)? Does the tailored amino acid supplement increase an antioxidant (complex amino acid) and decrease an amino acid associated with oxidative stress? Does the tailored amino acid supplement improve physical and mental health compared to a placebo supplement? Researchers will compare the tailored amino acid supplement to a placebo (a look-alike substance that contains no active ingredients) to see if the tailored amino acid supplements work to support health for people with Parkinson's disease. Participants will: Take the tailored amino acid supplement or a placebo every day for 6 months, visit the lab at baseline, after 3 months, and after 6 months for fasting blood draws, body composition assessment, and physical and mental health testing and keep a diary of their food intake and supplement intake.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by rigidity, tremor, postural instability, bradykinesia, and autonomic dysfunction. It is a common movement disorder worldwide. Motor impairments in PD patients are not limited to the muscles of the extremities; the neck, upper respiratory tract, and respiratory muscles are also affected. The resulting pulmonary dysfunction is one of the main factors contributing to morbidity and mortality in PD patients. Respiratory muscle exercise programs have been used to improve lung and swallowing function in patients with Parkinson's disease and other similar neurodegenerative disorders. Studies of inspiratory muscle exercise in Parkinson's patients have reported improvements in inspiratory muscle strength and endurance. Similarly, expiratory muscle exercise protocols have been shown to increase maximum expiratory pressure (MEP) and cough effectiveness. However, studies on expiratory muscle strengthening are lacking in the literature. Positive expiratory pressure (PEP) devices are used to clear airway secretions and feature a resistance that provides resistance during exhalation. This creates a positive pressure that stabilizes the airways during exhalation and prevents airway collapse. Although there are many PEP devices available on the market, the bottle-PEP, a therapist-made device, is used because it can be produced easily and at low cost. The bottle-PEP device consists of a bottle filled with at least 10 cm of water and a tube placed inside the bottle. Although information on strengthening expiratory muscles is traditionally found in the literature, there is no data in the literature on the effect of bottle-PEP use on expiratory muscle strength, especially in Parkinson's patients. A review of the literature shows that the effect of expiratory strengthening on balance has not been studied before. This study aimed to demonstrate the effects of the bottle-PEP device, used in addition to expiratory muscle strengthening, on expiratory muscle thickness, strength, and balance.

This is a Phase 2 study evaluating the positron-emitting radiopharmaceutical 18F-mFBG as an imaging agent for quantification of the effect of neurodegenerative diseases on myocardial sympathetic innervation. Effectiveness of 18F-mFBG imaging of the heart will be judged in terms of the quantitative difference between results for subjects with Lewy body and non-Lewy body neurologic disease as compared to historical data for healthy control subjects.

The aim of the study is to characterize the neuroinflammatory effects of subthalamic deep brain stimulation in patients with Parkinson's disease, by analyzing changes in blood neuroinflammatory and neurodegenerative biomarkers before and after surgery (at 6 and 12 months, respectively), and comparing the changes in blood biomarkers levels with a control group of patients with advanced PD on best medical treatment.

This prospective, randomized, single-blind, controlled clinical trial aims to evaluate and compare the efficacy of cognitive-based balance rehabilitation delivered via immersive Virtual Reality (VR) versus traditional Dual-Task Training (DTT) on balance, gait, cognitive functions, and quality of life in patients with Parkinson's Disease (PD). Postural instability and cognitive decline are hallmark features of progressive PD that significantly elevate fall risks and compromise daily independence, yet conventional pharmacological therapies offer limited effectiveness in restoring complex postural control. Given that motor and cognitive processes are intrinsically linked, this study addresses a critical gap in neurorehabilitation by investigating two contemporary modalities designed to challenge these systems simultaneously. A total of 34 participants diagnosed with PD (aged 40-80 years, Hoehn and Yahr stages I-III) will be randomly allocated to either the Dual-Task Group (DTG), receiving structured therapeutic exercises integrated with sequential cognitive tasks, or the Virtual Reality Group (VRG), engaging in an immersive balance program utilizing the Oculus Quest 2® headset with the FIT-XR application. Both groups will undergo an identical intervention protocol consisting of 45-minute supervised sessions, conducted twice weekly for 8 consecutive weeks during their pharmacological "on" phase. Standardized assessments will be performed by a blinded clinician at baseline and post-intervention (Week 8). The primary outcome measures will be dynamic balance and gait assessed through the Mini-Balance Evaluations Systems Test (Mini-BESTest) alongside global cognitive performance measured via the Montreal Cognitive Assessment (MoCA). Secondary outcomes will encompass objective posturographic indices using the Biodex Balance System, motor severity via the Unified Parkinson's Disease Rating Scale (UPDRS-III), freezing of gait, health-related quality of life, global perceived improvement, and potential cyber-sickness symptoms monitored through the Virtual Reality Sickness Questionnaire (VRSQ) to comprehensively determine the safety and comparative therapeutic value of these interventions.

The purpose of this pilot study is to identify the effects of active versus passive music therapy on functional ability and psychophysiological responses to goal-directed exercise in people with Parkinson's disease.

Dopason is a phase I, open-label, multicenter, single-arm clinical trial designed to evaluate the safety and feasibility of intraputaminal transplantation of human embryonic stem cell-derived dopaminergic progenitor cells (DopaCells) in patients with moderately severe Parkinson's disease.

This is an open-label, single-center Phase 1 study evaluating the safety, tolerability, and test-retest characteristics of \[11C\]MODAG-005, an investigational positron emission tomography/computed tomography (PET/CT) radioligand intended to image pathological alpha-synuclein deposition in the brain. The study will enroll participants with Parkinson's disease (PD), participants with multiple system atrophy (MSA), and age-matched healthy controls (AMHC). Participants with PD or MSA will undergo two \[11C\]MODAG-005 PET/CT imaging sessions: one baseline scan and one follow-up scan 7 to 48 days later. Age-matched healthy controls will undergo one baseline scan. A subset of PD and MSA participants will receive a single oral dose of anle138b (Emrusolmin) before the second scan to evaluate tracer uptake under blocking conditions. The primary objective is to assess the safety and tolerability of \[11C\]MODAG-005. Secondary objectives include evaluating whether \[11C\]MODAG-005 PET imaging can distinguish participants with MSA or PD from age-matched healthy controls, distinguish PD from MSA, and determine test-retest variability of PET outcome measures.

This clinical study, designed as a randomized, double-blind, placebo-controlled trial, aims to investigate if modulation of the N-methyl-D-aspartate receptor (NMDAR) via its co-agonist D-serine has therapeutic benefits in Parkinson's disease (PD). All patients will receive both placebo and D-serine over different time periods during the study. Preclinical studies have shown that blocking glycine transporters, which elevates endogenous glycine levels, can restore NMDAR function and improve motor deficits in PD models. A clinical trial demonstrated that oral D-serine (30 mg/kg/day for 6 weeks) significantly reduced extrapyramidal and abnormal involuntary movements in PD patients compared to placebo, with improvements observed in both motor and non-motor symptoms. D-serine supplementation has shown an acceptable safety profile with doses up to 120 mg/kg showing no significant adverse effects in clinical studies. The D-SPARK trial primarily aims to determine the efficacy of D-serine supplementation on clinical severity of PD as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Secondary aims are to determine the efficacy of D-serine supplementation on improving dopaminergic nigrostriatal innervation as measured by single-photon emission tomography (SPECT) based imaging of the dopamine transporter (DaT-scan) and cognition as measured by the California Verbal Learning Test version 2 (CLVT-II). The study will include 100 persons with Parkinson's disease (PwPD) diagnosed no longer than 5 years before baseline. Participants will be randomly assigned to receive D-Serine 4000 mg daily or placebo for defined periods of time during a 58 week treatment period, followed by a 12 week washout period. Participants will undergo: * Clinical evaluations, including clinical rating scales and questionnaires. * Cognitive assessments. * Bio sampling of whole blood and blood plasma. * Single-photon emission tomography (SPECT) imaging of dopamine transporter levels (DaT-scan) The outcomes of this study could potentially demonstrate that D-serine reduces symptom severity in Parkinson's disease and/or has an impact on the clinical trajectory of Parkinson's disease, benefiting persons living with Parkinson's disease, their families and society as a whole.

The investigators propose a Stage-I randomized controlled trial (RCT) of a remotely-delivered, 16-week social-cognitive theory-based behavioral intervention focusing on combined exercise (aerobic and resistance) training for yielding increases in device-measured physical activity and improvements in cognitive function, symptoms, and quality of life (QOL), and social-cognitive theory (SCT) outcomes among physically inactive persons with Parkinson's disease (PD). Participants (N=50) will be randomly assigned into exercise training (combined aerobic and resistance exercise) condition or active control (flexibility and stretching) condition. The 16-week intervention will be delivered and monitored remotely within a participant\'s home/community and supported by Zoom-based chats guided by SCT via a behavioral coach. Participants will receive training materials (e.g., prescriptive manual and exercise equipment), one-on-one coaching, action-planning via calendars, self-monitoring via logs, and SCT-based newsletters. The investigators hypothesize that the home-based exercise intervention will yield improvements in cognitive, symptomatic, and QOL outcomes.

The goal of this clinical trial is to investigate the effects of dual-task training on upper extremity function and muscle thickness in individuals with Parkinson's disease. The main questions it aims to answer are: Does dual-task training improve upper extremity function in individuals with Parkinson's disease? Does dual-task training lead to changes in upper extremity muscle thickness measured by ultrasonography? Researchers will compare a dual-task training group with a control group receiving routine care to determine whether 8 weeks of dual-task training results in greater improvements in upper extremity outco Participants will: complete baseline and post-intervention assessments of upper extremity function, muscle thickness, grip strength, and pinch strength be assigned to either a control group or a dual-task training group receive dual-task training 3 days per week for 8 weeks if assigned to the intervention group

This is an unblinded, non-randomized National Institute of Health (NIH) Stage I of Behavioral Intervention Development trial. The investigators will enroll 20 subjects with Parkinson disease (PD) for a series of 20 of N-of-1 trials. The investigators will use a single-arm crossover titration/reversal design ("ON" \[A\] vs. "OFF" \[B\]) with up to 4 periods. All participants will follow the sequence ABAB. Each period will last up to 10 weeks, allowing for sufficient time for up-titration and onset of drug action, and down-titration and washout. Each participant will have the option to participate in less (2-3) or more (3-4) periods depending on whether additional information is needed to make an informed decision about continuing or discontinuing the overactive bladder (OAB) antimuscarinic at the end of the study. The intervention drug will be an OAB antimuscarinic, previously prescribed to the participants by their physician. The investigators will reduce the dose of each OAB antimuscarinic by 25-50% every 1-2 weeks during the "OFF" \[B\] period, with the goal to completely discontinue the medication.

Preclinical human trials will be utilized to validate the research direction, followed by clinical trials to assess the impact of a cocktail formula product containing the optimal probiotic Y7 combined metabolites on motor, cognitive, and non-motor functions in early Parkinson's disease patients. The study aims to recruit 120 patients (stage 1-3) and employ a two-arm, randomized controlled trial (RCT) design, dividing subjects into intervention and control groups for a 12 weeks trial period. Commercial development will be contingent upon the clinical trial outcomes, evaluating whether the product offers clinical benefits such as delaying Parkinson's disease progression in motor, cognitive, and non-motor functions. Additionally, a personalized and precise prognosis prediction model for Parkinson's disease will be established. This model will gather comprehensive clinical data, including motor function assessments (functional tests, UPDRS), biochemical markers, questionnaire responses, and genotype data (TPM array), as well as metabolite and microbial data. Through integrated analysis of this biological information using machine learning techniques, a personalized and accurate prognosis prediction model for Parkinson's disease will be developed. This model will predict the disease status of PD patients 12 weeks later, accounting for factors such as cocktail therapy. The results will empower PD patients to understand their individual disease progression and treatment prognosis, enabling them to prepare accordingly. Moreover, this model will aid researchers in identifying patient profiles more likely to benefit from treatment, thereby enhancing the evaluation of the efficacy and applicability of cocktail therapy.

This study aims to determine whether electrical stimulation of the ear, when combined with physical and speech therapy, can improve symptoms in subjects diagnosed with Parkinson´s disease, by comparing two different application sites. Each subject will undergo an initial in-person screening and provide consent before participating in the study. The main questions to answer are: * Does transcutaneous electrical nerve stimulation (tVNS) in the ear paired with physical and speech therapy improve speech and voice-related problems, airway protection, salivation, and swallowing? * Does tVNS paired with physical and speech therapy improve tremor, walking speed, and balance in people with PD? * Does tVNS paired with physical and speech therapy improve heart rate and heart rate variability in people with PD? * Do its effects persist at 8 weeks? Participants will: Attend 12 rehabilitation sessions over 4 weeks (three per week). During each session, participants received either active or sham tVNS, accompanied by speech therapy (once per week), physical therapy (once per week), or conducted alone (once per week). Undergo speech, voice, swallowing, respiratory, gait, balance, tremor, heart rate variability, and cognitive testing, as well as questionnaires regarding the quality of life, before and after treatment. Return for a follow-up visit eight weeks after therapy to check how long the effects last.

This prospective, randomized, assessor-blinded clinical trial aims to compare the effects of robot-assisted gait training and quadriceps neuromuscular electrical stimulation (NMES) when added to a standard exercise rehabilitation program in patients with Parkinson disease. Participants will be randomly assigned to two parallel groups. Both groups will receive a standard rehabilitation program, while one group will additionally undergo robot-assisted gait training and the other group will receive quadriceps NMES. The interventions will be administered five days per week for six weeks. Clinical outcomes, including balance, functional mobility, gait performance, and disease severity, will be evaluated at baseline, post-treatment, and follow-up (week 14). In addition, ultrasound-based assessments of quadriceps muscle thickness and cross-sectional area will be performed to investigate muscle adaptations. The results of this study are expected to provide comparative evidence regarding the effectiveness of these two rehabilitation approaches and contribute to optimizing rehabilitation strategies in Parkinson disease.

Parkinson's disease (PD) is a common neurodegenerative disorder in middle-aged and elderly individuals, with a global incidence of 2.0% among adults aged 65 and over. Its pathogenesis remains unclear, and effective preventive and therapeutic approaches are lacking. PD severely impairs patients' physical and mental health and quality of life, while also imposing a substantial burden on families and society. This study will enroll patients with idiopathic PD diagnosed in the Department of Neurology, Fujian Medical University Union Hospital, from 2026 to 2036 to establish a research cohort. Using a non-interventional design, participants will undergo long-term follow-up through regular clinical visits, scale-based assessments, imaging examinations, and biological specimen testing. Corresponding data will be collected to build a research platform, aiming to clarify the pattern of disease progression and identify early diagnostic biomarkers. All testing methods are safe and reliable and will not pose additional risks to patients. This study will be conducted in strict compliance with ethical requirements. Prior to enrollment, patients will be fully informed of the study details and will voluntarily provide written informed consent. To mitigate the risk of privacy disclosure, measures including coded management, data encryption, and access restriction will be implemented throughout the study to protect participants' privacy, safeguard their legitimate rights and interests, avoid additional financial burdens, and ensure the study is conducted in a standardized manner. I hereby pledge to protect the personal privacy of all study participants and respect their autonomy. The study will be conducted in accordance with the principles of the Declaration of Helsinki and the Ethical Review Measures for Life Sciences and Medical Research Involving Human Subjects.

Parkinson's disease (PD) is a progressive neurological condition that can affect movement, balance, endurance, and overall quality of life. Exercise is widely recognized as one of the most effective non-pharmacological treatments to help people with PD maintain function and independence. However, not all exercise programs produce the same results, and more research is needed to understand which types of exercise offer the greatest physical and physiological benefits. This study is designed to examine how different types of structured exercise programs influence motor function, cardiorespiratory fitness, and markers of overall health in individuals with Parkinson's disease. The goal is to better understand how exercise can be used to improve movement, daily activities, and general well-being, as well as how it affects the body at a physiological level. Participants will be adults diagnosed with idiopathic Parkinson's disease who are medically stable and able to safely participate in exercise. Before beginning the study, participants will complete screening procedures to ensure safety and eligibility. Eligible participants will then be assigned to one of several supervised exercise interventions conducted over a defined period. Each exercise program is designed to improve movement and function but differs in structure or training emphasis (for example, aerobic, functional, or task-specific activity). Exercise sessions will take place under the supervision of licensed physical therapist. Each session will include warm-up, exercise, and cool-down components. Intensity will be monitored using heart rate and perceived exertion to ensure safety and appropriate challenge. Participants will attend sessions multiple times per week for 8 weeks. Researchers will collect information about movement abilities, balance, walking, endurance, and daily function using standardized physical therapy assessments such as gait tests, balance measures, and questionnaires related to quality of life at baseline, after 8-weeks of intervention and once more after a 4-week follow-up. In addition, blood samples will be collected to analyze physiological responses to exercise at the same 3 testing intervals. These samples will allow investigators to measure biomarkers related to cardiovascular health, nitric oxide availability, oxidative stress, and inflammation. These biological indicators can help identify how exercise affects underlying health mechanisms that may contribute to improved function in people with Parkinson's disease. All data will be collected by trained research personnel who are experienced in working with individuals with Parkinson's disease. Participants will be monitored for safety at each session, and any adverse events will be documented and reviewed by the principal investigator and the Institutional Review Board (IRB). By comparing changes across the different exercise programs, this study aims to determine which interventions have the most meaningful impact on mobility, endurance, and quality of life, as well as which ones produce measurable physiological benefits. Results from this research may help guide physical therapists, rehabilitation professionals, and people with Parkinson's disease in choosing the most effective exercise approaches for maintaining function and promoting overall health. Ultimately, this project seeks to contribute to the growing evidence that targeted, engaging, and appropriately dosed exercise can play a key role in improving the lives of people living with Parkinson's disease. The findings may also help inform future clinical practice guidelines, community exercise programs, and long-term wellness strategies for individuals with movement disorders.

A Phase I/II Clinical Study to Evaluate the Tolerability, Safety, and Efficacy of VGN-R08b Intra-cerebroventricular injection in Parkinson's Disease Patients with GBA1 Mutations

The purpose of this research study is to identify the role that the gut-brain axis, the group of nerves that connect the brain and gut, plays in Parkinson's disease (PD). The National Institute of Diabetes and Digestive and Kidney Diseases is sponsoring this research study. During this study, specific groups of participants, also known as "cohorts", will be identified based on the severity of their PD. There will also be a cohort enrolling participants who do not have Parkinson's and a cohort enrolling participants that are at risk for developing PD. Each of these cohorts will be compared to the others to assess the differences in the gut-brain connection. Participants in this study will: * meet with a medical provider * answer questionnaires * give samples of blood, stool, and saliva * have X-rays taken while swallowing different foods (swallowing study) * have X-rays taken to see how long it takes markers to move through their colon (colon transit study) * have a flexible sigmoidoscopy, where a doctor looks inside the lower part of the colon and takes small tissue samples (biopsies) from the mucosa (lining) * have samples taken of their skin * have an anorectal manometry and a balloon expulsion test, where a small tube and balloon are placed in the rectum to measure muscle function. Participation in the study will last up to 24 months (2 years).

The aim of this study is to examine the benefits that individuals with Parkinson's disease will gain from the rehabilitation program by enabling them to manage their exercise times independently using telerehabilitation method. The main research questions examined in this study are as follows: * Are the improvements in quality of life, walking speed and changes in functionality parameters achieved by individuals with Parkinson's disease through managing their own exercise plans as effective as those achieved through a supervised exercise programme? * Is it effective for Parkinson's patients to manage their own exercise plans in improving their adherence to exercise?

People with Parkinson's disease (PD) may have difficulty stopping or changing their movements, especially when walking around obstacles. The goal of this observational study is to learn if a specific cognitive function, called inhibitory control (the ability to stop or control actions) is associated with gait adaptability in people with Parkinson's disease. Gait adaptability means the ability to adjust how a person walks in response to changes in the environment, such as stepping over obstacles. The main questions the study aims to answer are: * If brain activation related to inhibitory control, measured by EEG, is associated with gait adaptability during obstacle crossing in people with Parkinson's disease? * If behavioral inhibitory control is associated with gait adaptability during obstacle crossing in people with Parkinson's disease? Participants take part in one study visit. During this visit, participants complete simple thinking tests, have their brain activity recorded using EEG, and perform walking tasks that include stepping over obstacles.

The aim of this study is to examine the effects of a specialized multi-modal intervention in patients with moderate to advanced Parkinson's disease (PD). The hypothesis is that a specialized motor- and cognitive exercise program in addition to usual care can improve gait and balance better than usual care alone. 48 patients with PD and a symptom duration of 4 or more years will be randomized 1:1 to either a control arm or to an intervention arm. The control arm will have usual management of their PD. The intervention arm will receive exercises aimed at both motor and cognitive impairments of PD over the course of 12 weeks. The study has been designed in partnership with the Copenhagen Trial Unit (CTU), Copenhagen Univeristy Hospital, to ensure both internal and external validity. To increase reproducibility, detailed protocols for all training modalities will be shared along with the study results. This study is a feasibility study with the intention of a following international multi-center study to corroborate the results. Both feasibility outcomes for the intervention itself and clinical outcomes for the participants will be published.

Parkinson's disease (PD) presents a complex challenge due to its progressive neurodegenerative nature, affecting various bodily systems. Despite decades of research, understanding its onset and progression remains unclear, complicating early diagnosis and treatment. Recent advances in PD pathophysiology suggest promising treatments to slow disease progression, yet reversing cellular degeneration remains elusive. With novel therapies emerging, the need for early detection tools is urgent. However, validated biomarkers for PD diagnosis are lacking, relying on subjective scales like Hoehn and Yahr or costly medical imaging techniques. The accumulation of misfolded α-Synuclein (α-Syn) proteins in PD pathology has sparked interest, but defining diagnostic roles requires further investigation. Recent findings of α-Syn in neuronal-derived extracellular vesicles (NDEVs) from PD patients suggest a potential for novel diagnostic methods. Our proposed project, VαMPiRE, aims to conduct a longitudinal study involving 600 PD and 600 non-PD participants using a cluster-adjusted case-control methodology, to explore α-Syn isoforms and related biomarkers in NDEVs for early PD detection. We plan to develop and validate an innovative in-vitro diagnostic (IVD) test capable of detecting PD's earliest stages and estimating disease prognosis and progression. Utilizing AI models to generate data analysis algorithms and collaboration with leading analytical laboratories and IVD manufacturers, we aim to ensure the reliability and feasibility of the developed prototype. Through consortium efforts, we envision licensing the generated intellectual property to drive the commercialization of our results. Two round of blood sample extractions will be performed within a 24-month gap to PD participants and a single baseline for non-PD controls. All participants will be regularly followed up during this 24-month period to monitor disease evolution and treatment, and non-PD controls developing the disease will be part of a third cohort (expected to be around 24 subjects according to 4% incidence) that will confirm the sensitivity of the test in asymptomatic subjects. The unique aspect of the project is that we anticipate being able to detect theses 4% of non-PD participants that will go on to develop the disease, therefore demonstrating the value of these biomarkers to identify PD early. The prototype will be validated for its discriminative capacity, using the first baseline set of PD and non-PD samples, and for its ability to detect the PD-progression comparing baseline and 24-months data plus blood samples. Improved early screening could allow for 270,000 new cases of PD to be detected earlier, improve the disease management of 9.4 M people currently diagnosed of PD and avoid losing a total of 5.8 million disability adjusted life years (DALYs) by 2028 leading also the development of better treatments.

This observational study aims to explore the use of the DANU Smart Socks for gait and balance assessment in people with Parkinson's (PwP). The study will compare walking and balance outcomes produced by DANU from people with Parkinson's (PwP) and a group of healthy individuals of similar age. The project aims to investigate if the gait and balance data collected are linked to measures of Parkinson's symptoms such as disease progression and cognitive abilities. Gait and balance outcomes will be obtained through one observational laboratory visit.