Parkinson's Disease (PD)

The purpose of this study is to understand whether people with Parkinson's Disease and depression have improvement in their symptoms after psilocybin therapy.

The goal of this clinical trial is to learn if home-based transcutaneous cervical vagus nerve stimulation (tcVNS) can improve symptoms in adults with Parkinson's disease. tcVNS uses a small portable device placed on the skin of the left side of the neck to deliver mild electrical stimulation. It does not require surgery or anesthesia. The main questions it aims to answer are: * Does tcVNS reduce non-motor symptoms of Parkinson's disease, such as sleep problems, low mood, anxiety, digestive problems, and fatigue? * Does tcVNS change movement symptoms, memory and thinking, brain wave activity, heart rhythm patterns, and markers of inflammation in the blood? * Can participants use the device safely on their own at home every day, and what medical problems do they have while using it? Everyone in this study will use the same stimulation device. There is no placebo group. Researchers will compare each participant's own measurements taken before stimulation, after 4 weeks of stimulation, and again after a 4-week break, to see whether symptoms change and whether any change lasts. Participants will: * Use the stimulation device on the neck for 30 minutes once a day, at home, every day for 4 weeks. The first session is done at the clinic with study staff, who teach participants how to use the device. * Visit the clinic 6 times over about 9 weeks for physical and neurological checkups, questionnaires about their symptoms, memory and thinking tests, brain wave recordings (EEG), and heart rhythm recordings (HRV). * Give a blood sample of about 10 mL at 3 of the visits (about 30 mL in total) so researchers can measure markers of inflammation. * Have a brain MRI scan at 2 of the visits, at centers where MRI is available. * Keep a record of their device use in a paper diary or a smartphone app. The device also records use times automatically.

This study will examine the long-term safety of buntanetap in participants with PD. This will be a 36-month open-label safety study. This study will be conducted with two cohorts. Cohort 1 will enroll via invitation only for PD participants who have previously participated in buntanetap clinical trials. Cohort 2 will be for PD participants who are receiving deep brain stimulation (DBS) treatment. Qualified participants will receive buntanetap 30mg QD after a screening period of up to 42 days.

Reducing balance problems and anxiety severity are the top two research uncertainties for people with Parkinson's disease (PD). Besides having a mutually aggravating relationship between postural impairment and anxiety severity, dual tasking is a critical condition that would increase postural instability and anxiety level concurrently. High-intensity aerobic exercise could improve balance and reduce anxiety. However, the training benefits from high-intensity aerobic exercise are limited in people with PD due to disease-related symptoms. Blood flow restriction (BFR) has been applied to low-intensity exercise. By creating localized hypoxia and increasing metabolic stress, BFR could facilitate aerobic system and neural adaptations. However, for the PD population, only one study applied BFR to aerobic exercise with the research design of a single-case report, let alone investigating the effects of BFR aerobic exercise on postural control and anxiety level under a dual-task condition. With the measurements of behavioral performance, subjective anxiety questionnaire, skin conductance response, and electroencephalogram (EEG), the purpose of the 3-year research project is to investigate the effects of BFR aerobic exercise on dual-task postural performance, anxiety, and related brain activities in people with PD. In the first year, the investigators will investigate the immediate effect of one bout of BFR aerobic exercise on dual-task postural control and anxiety level. In the second and third years, the investigators will investigate the long-term training effects of BFR aerobic exercise on dual-task postural control, anxiety modulation, brain plasticity, and patient satisfaction. The present project is expected to have significant contributions to gaining a better insight into the neural correlates of balance and anxiety with BFR aerobic exercise, particularly under dual-task conditions, and provide an optimized rehabilitation strategy for people with PD in clinical practice.

The study is a longitudinal, single-center study to assess progression of \[18F\]AV-133 imaging in PD participants. Participants will be followed for up to 12 months. Approximately 45 PD participants and 5 healthy control participants will be recruited from the ongoing PPMI Clinical 002 study. Participants will be comprehensively assessed at Baseline and follow up according to the Schedule of Activities. Participants will undergo PET imaging assessments with \[18F\]AV-133. After tracer injection, participants will be imaged on PET cameras at each imaging timepoint-one with the NX camera and one with a standard PET camera-in accordance with the Image Acquisition Protocol (IAP).

The goal of this trial is to learn if MTX325 can be developed as a potential disease-modifying treatment for Parkinson's Disease. Parts 1-4 complete, Part 5 (multiple doses in patients with Parkinson's Disease) in progress.

Deep brain stimulation (DBS) is a surgical implant procedure for the treatment of Parkinson's Disease (PD) utilizing medical devices approved by the FDA. A novel approach to current DBS approaches is called "Coordinated Reset" DBS (CR-DBS) which uses different patterns of stimulation at lower currents and can address the limitations of traditional DBS (T-DBS) that uses continuous high amplitude and high frequency stimulation. This study will evaluate the safety and short-term efficacy of CR-DBS in PD. The results from this study will significantly advance the development of CR-DBS for the treatment of PD. Findings in this study will also provide the rationale for further development of this novel DBS approach for other neurological and psychiatric disorders.

The currently available treatments of Parkinson's disease (PD) and Essential Tremor (ET) are inadequate and accompanied by adverse side effects making the treatment much less effective. This includes treatments with pharmaceuticals as well as electrical brain stimulation (DBS; Deep Brain Stimulation). To address this challenge, we have systematically worked to identify and overcome the shortcomings with current brain stimulation. Essential has been to achieve an understanding of the mechanisms behind the ubiquitous tissue reactions (often referred to as "foreign body reactions"), with loss of nerve cells near implanted electrodes and how to accomplish minimal tissue reactions/damage, which is necessary to enable therapeutically efficient low-intensity stimulation at precise locations. A further challenge relates to individual differences at the level of neuronal networks, making the exact sites in the brain that cause therapeutic and adverse side effects when stimulated not known in advance and thus requiring individual determination. Our strategy has therefore been to develop highly biocompatible microelectrodes (thinner than a human hair and highly flexible) and a guiding investigational device for controlled insertion of a cluster of such microelectrodes in deep target tissue. This enables individualized selection of appropriate stimulation sites. This technique, termed by us "High Definition Brain Stimulation" (HDBS), proved remarkably successful in animal models of both Parkinson's disease and pain by reliably providing powerful symptom relief without noticeable adverse side effects. For this first in human (FIH) investigation of microelectrode-based brain stimulation, we have systematically minimized all identified and foreseeable risks through optimization of the microelectrodes, the design of the investigational device for HDBS and development of simple minimally invasive surgical insertion methods. Extensive monitored safety tests in animals have confirmed the picture of negligeable tissue reactions/damage and absence of bleeding in the target area. Biological safety is also ensured by using only well-established materials documented for chronic implantation in the brain, established sterilization methods, identified safe stimulation intensities, and that the insertion procedures are adapted to well-established precision neurosurgical instruments and routines. The study is an early (FIH) feasibility clinical investigation which will be conducted in up to 12 patients with Parkinson's disease and/or Essential Tremor who are already scheduled for implantation of established DBS. The HDBS device will be inserted into awake patients in the same track as planned for the established DBS electrode. The evaluation will follow a protocol that includes stimulation of predetermined subsets of microelectrodes at up to 4 predetermined levels (depth) in the brain. The stimulation intensity for each subgroup is gradually increased until either a therapeutic effect or an undesirable side effect has been achieved. If an unacceptable effect is elicited, stimulation is immediately interrupted and a new subset of electrodes will be tested. After completion of the evaluation, the HDBS cluster electrode is removed and the implantation of an established permanent DBS electrode is completed. The evaluation will take up to 2.5 hours per patient. The patient's verbal responses, gestures, changes (if any) in tremors, rigidity, speech ability (such as slurring) or facial expressions before, during and after stimulation will be linked to the stimulation parameters (stimulation intensity, subgroup of microelectrodes, depth in the brain and time of reaction) and documented in writing and through video recordings. The analysis will only be made on anonymized data. The primary objective of this early feasibility, FIH, clinical investigation is to clarify whether HDBS (High Definition Brain Stimulation), through individualized stimulation of appropriate subgroups of implanted biocompatible microelectrodes, can provide a powerful therapeutic effect with minimal negative side effects also in humans. In addition, it is intended to simultaneously obtain important information that can be used by the neurosurgeon to improve the subsequent placement of the already scheduled permanent DBS electrode in the individual patient and thereby improve the treatment. Consequently, the secondary objective is to clarify whether HDBS can be used by the neurosurgeon to improve the placement of a permanent DBS electrode. The project paves the way for permanent HDBS with completely new opportunities for powerful, sustainable therapy with minimal side-effects in Parkinson's disease, Essential Tremor and other intractable neurologic disorders. Moreover, the HDBS technology enables new and potent opportunities for brain research.

This study will evaluate whether metformin when it will be given to patients with Parkinson's disease along with standard therapy (levodopa carbidopa) will improve motor symptoms and decreases levels of alpha synuclein and MDA in patients with PD as compare to PD patients receiving only standard therapy (levodopa carbidopa)

With this study, the investigators want to investigate how deep brain stimulation (DBS) affects various cognitive and psychiatric symptoms of Parkinson's disease (PD). In particular, they will examine whether stimulation of the left hemisphere has a different effect than stimulation of the right hemisphere on cognitive and psychiatric symptoms.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by different motor symptoms, including tremor, which is particularly difficult to manage. Common treatments, such as dopaminergic therapy, can have limitations in efficacy. Recent advancements in non-invasive brain stimulation, specifically phase-adaptive transcranial alternating current stimulation (tACS), offer a promising approach to reduce PD tremor. In the current project, a newly developed closed-loop system delivers precisely synchronized cerebellar tACS by aligning stimulation with the intrinsic hand tremor signal. The study will assess the efficacy of this novel approach to reduce hand tremor in PD patients.

The non-randomized, open-label phase I study aims to evaluate the safety, tolerability, biodistribution, radiation dosimetry, and pharmacokinetics of SST001 in healthy volunteers, patients with MSA and patients with PD.

The aim of this study is to contribute to and continue to sustain a repository of blood samples, nucleic acid (DNA and/or RNA) samples, family history information, and other demographic information from individuals with age-related neurodegenerative conditions, or their family members who may or may not be at risk for similar conditions. This study will continue to further expand research into the molecular and genetic basis of these diseases and their risk factors.

This study is looking at whether a gene therapy called AAV2-hAADC is safe and may help people with Parkinson's Disease. AAV2-hAADC is intended to increase the levels of dopamine in your brain. It contains a virus called adeno-associated virus 2 (AAV2) that has been modified to carry the genetic code for an enzyme called Aromatic L-Amino Acid Decarboxylase, or AADC for short. In this study, AAV2-hAADC is delivered to two parts of the brain called the putamen and the caudate. Increasing the amount of AADC gene in these parts of the brain converts more levodopa into dopamine, the chemical that is lacking in PD.

Comprehensive characterization of early-stage Parkinson's disease in patients with REM sleep behavior disorder Parkinson's disease (PD) is the fastest-growing neurodegenerative disorder worldwide, significantly affecting quality of life and causing substantial social and economic burdens. Currently, treatments for Parkinson's disease primarily manage symptoms through medication and lifestyle changes but cannot stop disease progression. By the time Parkinson's disease is diagnosed, substantial nerve-cell loss has already occurred in specific brain areas. Identifying early signs of PD before symptoms fully develop is essential for improving future treatment strategies. This research project aims to deeply understand the earliest stages of Parkinson's disease by studying patients with REM sleep behavior disorder (RBD). RBD is a condition characterized by unusual movements or behaviors during dream sleep, caused by nerve-cell loss in the brainstem. Importantly, more than 80% of individuals with RBD eventually develop Parkinson's disease or related conditions, such as Dementia with Lewy Bodies or Multiple System Atrophy. Study Goals: Our study will examine multiple potential biomarkers (measurable indicators) that could help identify early stages of Parkinson's disease. These include: 1. Brain structure changes: The Investigators will use advanced imaging methods (7-Tesla MRI) to closely examine specific brain regions known to be affected early in Parkinson's disease, particularly the substantia nigra and the locus coeruleus (LC). The LC helps regulate sleep and wakefulness, and studies have shown it is damaged in patients with RBD and Parkinson's disease. Additionally, the investigators will use specialized imaging (Pe2i-PET and MIBG-scintigraphy) to measure dopamine availability and changes in heart nerve function. 2. Abnormal protein buildup (ɑ-synuclein): In Parkinson's disease, nerve-cell death is linked to abnormal clumping of a protein called ɑ-synuclein within cells. Detecting this abnormal protein buildup early might help identify who is at risk of developing Parkinson's disease. The investigators aim to explore how levels of ɑ-synuclein aggregation relate to other early signs of the disease. 3. Functional changes in brain and body: Polysomnography, an overnight sleep test recording brain (EEG) and heart (ECG) activity, is the best method for diagnosing RBD. The investigators will also measure brain activity during wakefulness to further understand early changes. 4. Symptoms and physical tests: Participants will undergo thorough clinical assessments, including motor and cognitive tests, as well as tests evaluating autonomic (automatic nervous system) function, such as cardiovascular responses using a tilt-table test. Together, these extensive assessments will provide a detailed understanding of how Parkinson's disease begins and progresses. This knowledge can greatly improve early diagnosis, allowing earlier and potentially more effective treatments for individuals at high risk. Study Design: The investigators will recruit: * 50 individuals diagnosed with REM sleep behavior disorder * 50 control participants without major psychiatric or neurological disease, matched by age and gender THe investigation team have a complete, detailed plan and will begin collecting data as soon as ethical approval is granted. Main Hypotheses: Although our extensive data will allow many analyses, the investigation team specifically predict: * Individuals with RBD will show more significant damage in the locus coeruleus compared to controls. * Greater damage in the locus coeruleus will correlate with more severe cognitive issues, sleep problems, and autonomic dysfunction. * Cognitive issues in RBD patients might correlate with specific patterns of damage in different parts of the locus coeruleus. For example, memory problems might be linked to more damage in the front (rostral) part of this region. Impact: This study will significantly enhance early detection of Parkinson's disease, paving the way for personalized medical approaches and potentially more effective treatments. Conducted by a multidisciplinary team of experts in brain imaging, sleep medicine, autonomic function, and protein aggregation, this research supports Denmark's leadership in precision clinical imaging and aligns closely with hospital research strategies aimed at understanding and treating chronic diseases. Ultimately, our goal is to improve personalized patient care for Parkinson's disease in the future.

The purpose of this research study is to examine the effects of a 3-month personalized community-based walking program using a digital music-based device designed for self-directed gait training in people with Parkinson disease (PD). The study uses music cues delivered through this digital device to improve walking outcomes. The investigators want to know if personalized music cueing through the digital device can improve walking quality, walking ability, daily walking amount and intensity, and quality of life, while helping walking feel more automatic and require less mental effort. Participants will take part in this research study for approximately 18 weeks in total. During this time, participants will complete 4 study visits at designated research centers at Boston University, Washington University in St. Louis, or the University of Utah, depending on the site of enrollment.

The goal of this clinical trial is to compare the efficacy and safety of different Intervention Intervals of subthalamic nucleus-targeted transcranial temporal interference stimulation (STN-tTIS) in patients with Parkinson disease. Previous studies suggest that STN-tTIS may improve motor symptoms in people with Parkinson disease. However, most previous studies evaluated only one stimulation session. It remains unclear how often STN-tTIS should be administered during a repeated treatment course and whether shorter intervention intervals stimulation produces greater or longer-lasting improvement without increasing adverse events. The main questions this study aims to answer are: 1. Does STN-tTIS administered five times weekly improve motor symptoms more than standard medication treatment alone at the end of the 2-week treatment period? 2. Do once-weekly, twice-weekly, and five-times-weekly STN-tTIS produce different changes in motor symptoms? 3. Does the STN-tTIS intervention intervals influence how long its effects persist after treatment? 4. Do the different intervention intervals have different effects on non-motor symptoms, quality of life, cognitive function, and safety? Participants will be randomly assigned to receive STN-tTIS once weekly, twice weekly, or five times weekly for 2 weeks, or to continue standard antiparkinsonian medication without additional stimulation. All participants will maintain a stable medication regimen during the study. Their motor and non-motor symptoms will be assessed during the treatment period and during a subsequent 2-week follow-up period.

This study seeks to understand the prevalence and variability of a gut bacteria gene called csgA in people with Parkinson's Disease. This understanding could inform development of potential new therapies targeting the gut in Parkinson's Disease.

The main goal of the study is to investigate how well the new drug SUL-238 works in Parkinson's Disease (PD). This is done by means of an MRS scan. An MRS scan is similar to a regular MRI scan. It will also learn about the safety of new drug SUL-238. The main questions it aims to answer are: * Does new drug SUL-238 improve the mitochondrial function in patients with Parkinson's Disease (PD)? * What medical problems do participants have when taking new drug SUL-238? Researchers will compare new drug SUL-238 to a placebo (a look-alike substance that contains no drug) to see if SUL-238 works to improve mitochondrial function in patients with PD. Participants will: * Take new drug SUL-238 or a placebo every day for 28 days * Visit the clinic once every 2 weeks for checkups and tests during the treatment period and finally 28 days after the last dose of SUL-238 * Keep a diary of their symptoms and the number of times they use oral new drug SUL-238

This study is a randomized, double-blind, multicenter, placebo-controlled Phase III clinical trial designed to evaluate the efficacy, safety, and Pop PK characteristics of TJ0113 Capsules in treating EOPD patients. This study plans to enroll approximately 300 EOPD participants, who will be randomized in a 1:1 ratio to two cohorts (Cohort 1: 200 mg dose group; Cohort 2: 400 mg dose group). Within each cohort, successfully screened participants will be stratified by stable use of dopamine receptor agonists (Yes vs. No) and stable use of Monoamine Oxidase B (MAO-B) inhibitors (Yes vs. No), and within each stratum, randomized in a 2:1 ratio to the TJ0113 Capsules group and the placebo group, with approximately 100 assigned to the TJ0113 Capsules group and approximately 50 assigned to the placebo group. In this trial, the sample size for the TJ0113 Capsules 200 mg group, TJ0113 Capsules 400 mg group, and placebo group will each be approximately 100 participants. After randomization, during the double-blind treatment period, participants will receive continuous oral administration of TJ0113 Capsules or placebo for 26 weeks. After the double-blind treatment ends, participants will enter the open-label treatment period. During the open-label treatment period, all participants will receive oral TJ0113 Capsules for 26 weeks, and the dose of TJ0113 Capsules will be consistent with the dose of the investigational product taken by the participant during the double-blind treatment period (regardless of whether they took TJ0113 Capsules or placebo during the double-blind treatment period). After the open-label treatment period ends, participants will continue to receive a safety follow-up for 1 week (telephone follow-up). From the screening period to the end of the double-blind treatment period, all participants must maintain their original background anti-PD medication regimen unchanged; from the open-label treatment period to the end of the study, changes to the dose of stably received anti-PD medications are discouraged, but if necessary, the dose may be adjusted at the discretion of the investigator.

Low intensity focused ultrasound (LIFUS) has the potential to be used as a means of non-invasive neuro-modulation. To this day, the use of LIFUS is under investigation. Studies in healthy subjects have shown that application of LIFUS to the motor region of the brain can mildly decrease neuron excitability in healthy controls. The purpose of the present study is to evaluate the effects of LIFUS on brain tissue excitability in patients with movement disorders in order to elucidate the therapeutic potential of LIFUS.

Study BRT-DA01-301 is a Phase 3 multicenter, randomized, sham surgery-controlled, double-blind study to assess efficacy and safety of bemdaneprocel in approximately 102 adults with Parkinson's Disease (PD).

This study aims to examine whether individual music therapy - involving the slow, gentle bowing of a string instrument, accompanied by the music therapist's singing and lyre playing - can have a relaxing and calming effect on patients with Parkinson's disease and improve anxiety, quality of life, and autonomic dysfunction such as unstable blood pressure. People with Parkinson's disease often struggle with anxiety, apathy, and depression, which can severely affect their quality of life. These symptoms are usually difficult to treat adequately with medication. They are frequently associated with dysfunction of the autonomic nervous system and a reduced variability of heart rate. Both are common in Parkinson's disease and can provide clues about stress and well-being. A healthy heart does not beat at completely regular intervals; instead, the time between beats constantly changes slightly. This fluctuation is called heart rate variability (HRV). Primary study outcome will be anxiety. Motivation, depression, individual quality of life, and severity of autonomic symptoms are also assessed using validated questionnaires. Physical study measures will be HRV, along with stability of blood pressure, intensity of tremor, ability to walk, and also electroencephalography (EEG) to assess brain activity. A subproject will explore whether listening to emotionally evocative music can specifically influence the brain in patients with Parkinson's disease (as measured by EEG) and autonomic functions (as measured by HRV). The effectiveness of an emotional response will be measured by a questionnaire (the Geneva Emotional Music Scale).

Parkinson's disease often causes speech and voice impairments, such as reduced vocal loudness and decreased speech intelligibility, which significantly impact the quality of life for patients and their families. The Lee Silverman Voice Therapy-LOUD (LSVT-LOUD) is a specialized, evidence-based speech therapy protocol designed to improve vocal function. This study investigates the effectiveness of the LSVT-LOUD protocol in Turkish-speaking individuals with Parkinson's disease. The research evaluates objective changes in vocal loudness and speech quality, as well as the subjective therapy experiences of participants. By analyzing both clinical outcomes and patient feedback, this study aims to contribute to the clinical application and adaptation of LSVT-LOUD for the Turkish-speaking population

This study aims to evaluate the safety, tolerability, and preliminary efficacy of ZR001, a novel chemogenetic gene therapy product, in patients with moderately advanced Parkinson's disease (PD). ZR001 is administered via stereotactic injection into the bilateral substantia nigra, followed by postoperative ultra-low-dose clozapine to activate the transduced direct pathway, with the goal of improving motor symptoms of Parkinson's disease.