Clinical Research Directory

AAV2-hAADC for Parkinson's Disease (PDCS-01)

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.

A Study of Buntanetap in Participants With PD

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.

Investigating Basal Ganglia-Cortical Physiology During Sleep and Its Modulation by Adaptive Deep Brain Stimulation in Parkinson Disease

This is an interventional study of a cohort of patients with PD treated with DBS, and already utilizing adaptive DBS (dual threshold mode). In Aim 1, we will obtain baseline sleep and basal ganglia physiology data to inform aDBS parameter changes. Aim 2 involves 15 nights of in-home monitoring of subjective and objective sleep quality, during which participants will use 3 different sleep-tailored aDBS settings at night only. Participant preference among these 3 settings will determined the 'optimized sleep-tailored aDBS mode'. Participants will undergo repeat polysomnography, while in the optimized sleep-tailored aDBS mode, to compare aDBS behavior and sleep architecture to the baseline (Aim 1) sleep study.

[18F]ACI-15916 PET in α-synucleinopathies

The goal of this clinical trial is to test whether we can reliably and safely measure the accumulation of pathological protein α-synuclein \[involved in some diseases such as Parkinson's disease, Lewy body dementia and Multiple System Atrophy (MSA), collectively named α-synucleinopathies\] using a new positron emission tomography (PET) tracer called \[18F\]ACI-15916. Both healthy people and people with (suspected) α-synuclein pathology will participate to this trial. The main questions it aims to answer are: * whether \[18F\]ACI-15916 is safe and well tolerated when injected into participants * whether \[18F\]ACI-15916 reliably detects α-synuclein in the brain using PET technique. * whether there are differences in the amount of this protein between people with diseases related to α-synuclein accumulation in the brain and people without these diseases. Participants will: * Visit the clinic to consent to their participation and to ensure they are eligible \[physical and neurological examinations, questionnaires, blood and urine tests, ECG and in some cases a MRI and a PET scan with a licensed tracer (\[18F\]FE-PE2I) to confirm or not the disease\]. * Visit the clinic to receive the tracer \[18F\]ACI-15916 intravenously and be scanned in a PET scanner, during which blood will be collected (and optionally spinal fluid). * Receive a phone call from the clinic 1 week after the PET scan to report any symptoms and side-effects that they may be having. Some of the participants may be asked to come again to the clinic for a second PET scan with \[18F\]ACI-15916, allowing the researchers to determine if the measurements with the first PET scan are stable and reproducible. Some of the participants will participate in a specific part of the study to evaluate the distribution of the PET ligand in the whole body, with a similar visit schedule.

Comparison of Two Different Dual-Task Training Methods in Patients With Parkinson's Disease

The aim of this study is to compare the effectiveness of motor-motor dual-task training and cognitive-motor dual-task training in patients with Parkinson's disease.The main questions it aims to answer are: \- Whether there is a difference between motor-motor dual-task training and cognitive-motor dual-task training in patients with Parkinson's disease in terms of their effects on motor symptoms, balance, gait, functional mobility, activities of daily living, dual-task activities, cognitive functions, and balance confidence. Researchers will compare single-task training, motor-motor dual task training and cogvitive-motor dual task training. Participants will: * Receive exercise training at the study clinic twice a week for approximately 45 minutes each time, for 6 weeks. * Participate in assessments at the study clinic before and after exercise training.

Effects of Vagal Nerve Stimulation on Leg Muscle Activity and Posture in Parkinson's Disease

This study is designed to better understand the mechanisms contributing to impaired activation of leg muscles in people with Parkinson's disease (PD) and to test if stimulation of a nerve at the neck can improve muscle activation, walking and balance.

A Phase I Study in Healthy Volunteers and Parkinson's Disease (PD) Patients.

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.

The Effects of Tele-Rehabilitation-Based Dual-Task Upper Extremity Training in Patients With Parkinson's Disease

The aim of this study is to compare the effects of tele-rehabilitation-based synchronous and asynchronous dual-task upper extremity training with clinical based dual-task upper extremity training and conventional single-task upper extremity training in patients with Parkinson's disease. The main questions it aims to answer are: * Whether there are differences in motor symptoms, hand dexterity, upper extremity functions, grip strength, executive functions, daily living activities, and treatment satisfaction between tele-rehabilitation-based synchronous and asynchronous dual-task upper extremity training, clinical-based dual-task upper extremity training, and conventional single-task upper extremity training in patients with Parkinson's disease. * Whether there is a difference in telemedicine satisfaction between tele-rehabilitation-based synchronous and asynchronous dual-task upper extremity training in patients with Parkinson's disease. Researchers will compare conventional single-task upper extremity training, clinical-based dual-task upper extremity training, tele-rehabilitation-based synchronous upper extremity training and tele-rehabilitation-based asynchronous upper extremity training. Participants will: * Receive upper extremity exercise training at the study clinic or home, twice a week for approximately 60 minutes each time, for 6 weeks. * Participate in assessments at the study clinic before and after exercise training.

Coordinated Reset Deep Brain Stimulation for Parkinson's Disease

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.

To Assess Self-sufficiency in Parkinson's Patients and How Rehabilitation Affects Symptoms Linked to Independence

This interventional study aims to assess self-sufficiency in patients with Parkinson's disease in the spa setting using the new Czech Functional Efficiency of Self-sufficiency Test (FEST) and to validate the test in this population. It also aims to evaluate changes in cognition, stability, fear of falling, and gait after specialized spa care and to analyze correlations between self-sufficiency and these outcomes.

Movement State-dependent Adaptive DBS for PD

This is a single-center clinical study aiming to improve gait functions in patients with Parkinson's Disease (PD) by using adaptive neurostimulation to the pallidum. The investigators will use a bidirectional deep brain stimulation device with sensing and stimulation capabilities to 1) identify neural biomarkers to detect the onset of walking by recording neural activities from the motor cortical areas and the globus pallidus, 2) understand the impacts of changes in DBS parameters on gait kinematics and optimize setting parameters for enhancing walking performance, 3) develop a movement state-dependent adaptive deep brain stimulation (DBS) paradigm to automatically switch stimulation settings according to different movement states (i.e., walking vs non-walking). The proposed therapy will deliver personalized neurostimulation based on individual physiological biomarkers to enhance gait function in patients with PD. 6 patients with idiopathic Parkinson's disease who have already been implanted with the Medtronic Summit RC+S device will be enrolled in this study.

Terazosin And Metabolic Energetics in Parkinson's Disease

This study investigates if Terazosin can improve metabolism in PD.

The Efficacy of Psilocybin Therapy for Depression in Parkinson's Disease

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

Effects of Transcutaneous Cervical Vagus Nerve Stimulation on Non-motor Symptoms in Parkinson's Disease

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.

Boxing-Based Training to Improve Balance and Mobility in Parkinson's Disease

The goal of this clinical trial is to learn if physical exercise that extensively and simultaneously challenges the brain's balance control network is effective in improving balance for people with mild to moderate Parkinson's disease. The study aims to test a specific hypothesis: that a physically demanding, "multidomain" program-which trains multiple areas of balance at the same time-will produce significantly better results than simple exercises that only partially address the balance network. To test this, researchers will use a specialized boxing-based program (EBA-B) as a model of challenging exercise. This will be compared to an active control group performing simple, low-intensity mobility movements in a chair. The main questions it aims to answer are: * Does exercise that simultaneously challenges multiple domains of balance (using boxing as a tool) produce superior global improvements compared to less demanding programs? * Is this extensive neural challenge more effective at reducing motor symptoms and improving functional mobility? Participants will: * Complete an 8-week "challenging" phase involving 50-minute group boxing sessions (EBA-B) 3 times per week, designed to challenge speed, agility, and coordination. * Complete an 8-week "simple exercise" phase involving 20-minute home-based mobility seated workout 5 times per week, along with weekly education talks. * Undergo clinical evaluations and balance tests at the start, middle, and end of the study to measure changes in their mobility

Blood Flow Restriction Aerobic Exercise for Balance and Anxiety in Parkinson's Disease

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.

This Protocol is a Sub-study Under the PPMI Program. It is a Longitudinal, Single-center Study to Assess the Performance of [18F]AV-133 Imaging Using High and Standard Resolution PET in Individuals Enrolled With Parkinson's Disease (PD) for up to 12 Months.

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).

Cerebellar Transcranial Alternating Current Stimulation (tACS) to Modulate Parkinson's Disease Tremor

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.

A Study to Evaluate Satety, Tolerability, Biodistribution, Radiation Dosimetry, and Pharmacokinetics of SST001 in Healthy Volunteers, Patients With PD and Patients With MSA

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.

Biofluid Research on Age-Related or Inherited Neurodegeneration

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.

A Comprehensive, Multimodal Characterization of Prodromal PD in Subjects With RBD

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.

A Novel Digital Music-based Autonomous Personalized Walking Intervention to Improve Gait and Walking Automaticity in Parkinson Disease

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.

STN-tTIS With Different Intervention Intervals Versus Standard Medical Treatment for Parkinson's Disease

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.

A Phase 2 Study to Assess the Effects of SUL-238 on High Energy Phosphates With ³¹P-MRS in Patients With Early, Untreated 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