Clinical Research Directory

PET Scanning in Parkinson s Disease

This is an in vivo positron emission tomography (PET) study of regional cerebral dopamine and blood flow in normal volunteers, persons with Parkinson s disease (both familial and sporadic), and those with schizophrenia spectrum disorders. The latter also sign consent for NIH approved protocol 89-M-0160, "Inpatient Evaluation of Neuropsychiatric Patients," PI: Daniel Eisenberg, M.D. Using PET with 6-\[F-18\] Fluoro-L-dopa (FDOPA) and (15)0-H2O in a single scan session, both presynaptic dopaminergic function and regional cerebral blood flow (rCBF) are assessed. The kinetic rate constant (Ki) for presynaptic dopaminergic uptake in striatum and other regions is calculated. We compare Ki across subject groups and relate the findings to rCBF. Findings are also related to allelic variation in genes of interest, for determination of which participants sign separate consent for NIH approved protocol 95-M-0150 Neurobiological Investigation of Patients with Schizophrenia Spectrum Disorders and Their Siblings, PI: Karen F. Berman, MD. We also draw comparisons between subjects with inherited vs. sporadic Parkinson s disease to determine whether the PET phenotype is the same in both groups, and we compare system-level, circuit-based pathophysiology across PD and schizophrenia groups. Each subject is further screened with an MRI to rule out structural abnormalities and also to further delineate areas of interest in the PET scans....

Agricultural Health Study Follow-up

Background: \- The Agricultural Health Study (AHS) is looking at the long-term health effects of farming exposures including pesticides, crops, and animals. The chronic health effects of exposure to pesticides are easier to study in farmers and their spouses. They know what chemicals they use and tend to live in the same place for most of their adult lives. AHS participants are expected to report any changes in their health. This includes any new medical conditions. Researchers want to follow up on these reports to confirm their accuracy. Objectives: \- To follow up AHS participants who have self-reported that they have a new disease and confirm their diagnosis. Eligibility: \- Current AHS participants. Design: * Researchers will confirm self-reported changes in medical conditions by contacting the AHS participant to ask for more information. * The AHS participant will give permission for researchers to contact their doctor to look at their medical records. They will also be asked to provide a cheek swab or saliva sample. * Diseases of interest are rheumatoid arthritis, lupus, and Sjogren s Syndrome. Other diseases will be followed up in the future. Other diseases will be followed up in the future.

Study to Assess Real Life Effectiveness of Foslevodopa/Foscarbidopa in Adult German Participants at Initial Stages of Advanced Parkinson's Disease (EARLY-FOS)

Parkinson's disease (PD) is a neurological condition, which affects the brain. PD gets worse over time, but how quickly it progresses varies a lot from person to person. Some symptoms of PD are tremors, stiffness, and slowness of movement. This study will assess how effective foscarbidopa/ foslevodopa is in treating German adult participants at initial stages of advanced Parkinson's disease under routine clinical practice. Foslevodopa/Foscarbidopa is an approved drug for the treatment of Parkinson's Disease. Approximately 125 adult participants who are prescribed Foslevodopa/Foscarbidopa by their doctors will be enrolled across approximately 20 sites in Germany. Participants will receive Foslevodopa/Foscarbidopa subcutaneous infusion as prescribed by their physician. Participants will be followed for up to 12 months. There is expected to be no additional burden for participants in this trial. Participants will attend regular visits during the study at a hospital or clinic according to their routine clinical practice.

Can Subthalamic Stimulation Using Directional Electrodes Improve Postoperative Management in Parkinson's Disease

The primary objective of the study is to determine if subthalamic nucleus (STN) deep brain stimulation (DBS) using the Vercise directional leads improves neuropsychiatric state and neuropsychiatric fluctuations 12 months after surgery in a large consecutive series of STN-DBS Parkinson's disease (PD) patients.

Deep Brain Stimulation Surgery for Movement Disorders

Background: \- Deep brain stimulation (DBS) is an approved surgery for certain movement disorders, like Parkinson's disease, that do not respond well to other treatments. DBS uses a battery-powered device called a neurostimulator (like a pacemaker) that is placed under the skin in the chest. It is used to stimulate the areas of the brain that affect movement. Stimulating these areas helps to block the nerve signals that cause abnormal movements. Researchers also want to record the brain function of people with movement disorders during the surgery. Objectives: * To study how DBS surgery affects Parkinson s disease, dystonia, and tremor. * To obtain information on brain and nerve cell function during DBS surgery. Eligibility: \- People at least 18 years of age who have movement disorders, like Parkinson's disease, essential tremor, and dystonia. Design: * Researchers will screen patients with physical and neurological exams to decide whether they can have the surgery. Patients will also have a medical history, blood tests, imaging studies, and other tests. Before the surgery, participants will practice movement and memory tests. * During surgery, the stimulator will be placed to provide the right amount of stimulation for the brain. Patients will perform the movement and memory tests that they practiced earlier. * After surgery, participants will recover in the hospital. They will have a followup visit within 4 weeks to turn on and adjust the stimulator. The stimulator has to be programmed and adjusted over weeks to months to find the best settings. * Participants will return for followup visits at 1, 2, and 3 months after surgery. Researchers will test their movement, memory, and general quality of life. Each visit will last about 2 hours.

Fecal Microbiota Transplantation in Parkinson's Disease.

Fecal microbiota transplantation (FMT) is an effective and safe treatment for Clostridioides difficile infection (CDI). Though CDI is the only indication for FMT, more and more preliminary data on FMT in neurological disorders are reported due to gut-brain axis. This study is a pilot study to apply FMT on patients with Parkinson's disease (PD). The effect of FMT on motor and non-motor symptoms in PD will be also evaluated.

A Clinical Trial of LY3962681 in Healthy Volunteers and in Patients With Parkinson's Disease

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics/pharmacodynamics (PK/PD) of LY3962681 in healthy volunteers and patients with Parkinson's disease. The study consists of two parts, the Single Ascending Dose (SAD) study and the Multiple Ascending Dose (MAD) study. During the SAD portion of the study, healthy volunteers will receive a single dose of LY3962681 or placebo (artificial cerebrospinal fluid \[aCSF\]) administered intrathecally (into the spinal fluid). During the MAD portion of the study, patients with Parkinson's disease will receive two doses of either LY3962681 or placebo (aCSF) administered intrathecally (into the spinal fluid), 12 to 24 weeks apart. * The treatment period in the SAD study will be 1 day. The treatment period in the MAD study will be 2 dosing days, 12 to 24 weeks apart. * The follow-up period in the SAD study will be up to 52 weeks. The follow-up period in the MAD study will be up to 52 weeks after Dose 2.

RESvEraTrol in Parkinson's Disease (RESET)

This is an exploratory phase 2a study to investigate two doses of resveratrol (JotrolTM) vs placebo in individuals diagnosed with Parkinson's Disease (PD). Participants (n=30) will be randomized 1:1:1 into 3 groups and will receive oral JotrolTM vs placebo. Study drug will be titrated to reach a final maximal dose per group and will be administered orally once daily (QD) for 3 months. The study will primarily evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics (PK/PD) of JotrolTM.

A US Study That Observes How Parkinson's Disease Changes Over Time in Patients Who Still Have Movement Symptoms Despite Taking Parkinson's Medications

This is an observational study in which data are collected and studied from Parkinson's disease patients who have movement symptoms despite taking standard Parkinson's medications. In observational studies, observations are made without any changes to the participant's healthcare or treatment plan. No investigational product will be administered in this study, as participants will be treated with the standard of care that medical experts currently consider most appropriate. Parkinson's disease (PD) is a condition that affects the brain and causes problems with movement and other body functions. The symptoms of Parkinson's disease can worsen over time. People with Parkinson's disease may experience shaking (tremor), slow movements, stiff muscles, trouble walking, and problems with balance. They can also have other symptoms, such as difficulty thinking clearly, changes in mood, or difficulty sleeping. Parkinson's disease mostly affects older adults, but it can happen to younger people too. There is no cure, but treatments can help manage the symptoms and improve quality of life. While doctors and researchers know that Parkinson's disease affects people in different ways and can worsen over time, there are still many things they don't fully understand-especially for people who experience movement symptoms despite taking their usual Parkinson's medicines. Earlier studies did not follow these patients long enough or collect all the important information needed. This study is being done to fill those gaps. The main purpose of this study is to better understand how Parkinson's disease changes over time in patients who experience movement symptoms while taking standard oral Parkinson's medications, what challenges patients and their care partners face, and how their treatments are working in real life. To do this, researchers will collect data on: * Sociodemographics (e.g. age, gender, race/ethnicity, insurance provider). * Medical history and vital signs (e.g. comorbidities, family history of Parkinson's, height, weight, blood pressure). * Medications and treatments (e.g. Parkinson's and non-Parkinson's medications and other treatments, rehabilitation therapy sessions, use of mobility assistance devices). * Movement symptoms (e.g. tremor, slow movement, balance). * Non-movement symptoms (e.g. cognition, mood, sleep, activities of daily living). * Molecular data (e.g. genetics, α-synuclein). * Burden of care (e.g. economic cost). Data will come from questionnaires or rating scales conducted by the doctor with the patient during study visits, diaries and logs completed by the patient, medical records, health insurance claims records, blood samples and skin biopsies, a digital device that records movement/non-movement symptoms, and questionnaires completed by the care partner. Data will be collected from December 2025 to December 2032. Each participant may be followed for up to 5 years.

Study of Methylphenidate to Treat Gait Disorders And Attention Deficit In Parkinson's Disease (PARKGAIT-II)

Therapeutic management of gait disorders in very advanced Parkinson's disease (PD) patients can sometimes be disappointing, since dopaminergic drug treatments and subthalamic nucleus (STN) stimulation are more effective for limb-related Parkinsonian signs than for gait disorders. Gait disorders could be also partly related to noradrenergic system impairment, pharmacological modulation of both dopamine and noradrenaline pathways could potentially improve the symptomatology. The investigators have demonstrated using an open label study on 17 advanced PD patients that chronic, high doses of methylphenidate (MPD) improved gait, freezing of gait, motor symptoms and attention in the absence of L-Dopa and increased the intensity of response of these symptoms to L-Dopa (Devos et al., 2007). The investigators aimed to confirm their results using a randomized, double-blind, placebo-controlled, parallel-group, multicentric trial. The investigators will assess the clinical value of chronic, high doses (1 mg/kg/day) of MPD vs placebo in 88 non demented PD patients suffering from severe gait disorders with freezing despite their use of optimal dopaminergic doses and eventually STN stimulation parameters. Efficacy will be assessed directly and on video in the absence of L-Dopa and again after acute administration of the drug, both before and after a 3-month course of MPD, using Stand Walk Sit test (primary criteria), the "Freezing Of Gait trajectory", RGSE scale, the UPDRS scores, the dyskinesia rating scale, Achiron scales and using auto-questionnaires of Giladi, ABC scale and PDQ 39. Attention will be assessed using reactions times. Drowsiness will be assessed using Epworth and Parkinson's disease Sleep Scales. Apathy and depression will be monitored with Lille Apathy Rating Scale, MADRS, BPRS, MINI and psychiatric interview. Cardiologic and general tolerance will be also monitored. This study could lead to propose methylphenidate with a good efficacy/ risk balance in advanced PD patients suffering from severe gait disorders with freezing of gait, drowsiness and attention deficit.

Efficacy, Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of BIA 28-6156 in GBA-PD

The purpose of this randomized, double-blind, placebo-controlled study is to assess the efficacy of BIA 28-6156 over placebo in delaying clinical meaningful motor progression over 78 weeks in subjects with Parkinson's disease who have a pathogenic variant in the glucocerebrosidase 1 (GBA1) gene (GBA-PD).

Repurposing Lithium for Parkinson's Disease

This study will examine the effects of lithium aspartate 30-45mg/day on MRI biomarkers and blood-based therapeutic targets among 15 early-stage Parkinson's disease patients.

A Study to Evaluate the Efficacy and Safety of Monosialotetrahexosylganglioside Sodium Injection in Parkinson's Disease Participants With Motor Fluctuations

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2 study. A total of 276 eligible Parkinson's disease participants with motor fluctuations will be enrolled and assigned to one of three cohorts. Within each cohort, participants will be randomized in a 3:1 ratio to receive either GM1 or matching placebo, resulting in six groups: Cohort 1 GM1 (n=69), Cohort 1 Placebo (n=23); Cohort 2 GM1 (n=69), Cohort 2 Placebo (n=23); Cohort 3 GM1 (n=69), Cohort 3 Placebo (n=23). All participants will continue their pre-enrollment anti-Parkinson's medication regimen as background therapy, which should remain as stable as possible during the study. The study consists of a 28-day screening period and an 85-day double-blind treatment period.

PET Imaging in Parkinson Disease Dementia

The purpose of this study is to use a brain imaging method called PIB PET to determine dementia subtypes in patients with Parkinson's disease. The ultimate goal of this project is to be able to identify individuals with PD who are at risk of developing dementia, and to distinguish the underlying cause of dementia.

Registry of Deep Brain Stimulation With the VERCISE™ System: Vercise DBS Registry

The purpose of this registry is to compile characteristics of world-wide outcomes for the use of Boston Scientific's commercially available Vercise DBS System in the treatment of Parkinson's disease. The utilization of Image Guided Programming (IGP), and other commercially available programming features, used as planning tools for the programming of patients with Boston Scientific's Vercise DBS System are also evaluated. Additionally, the utilization of the DBS Illumina 3D feature that may be used for the programming of patients with Boston Scientific's Vercise DBS Systems is also evaluated.

Individualized Transcranial Magnetic Stimulation in Parkinsonian Disorders

This clinical trial aims to evaluate whether individualized targeted repetitive transcranial magnetic stimulation (rTMS) can improve motor and non-motor symptoms in patients with parkinsonian disorders. The main question it aims to answer is: * Does individualized targeted rTMS alleviate symptoms of parkinsonian disorders? * Which clinical manifestations of parkinsonian syndromes are responsive to individualized targeted rTMS, and to what degree? Procedures: * Preparation (Screening) Participants will undergo clinical assessments, MRI, and EEG before the treatment. * Treatment (2 Weeks) Participants will receive a 10-day TMS treatment (once daily, Monday-Friday). Each treatment day takes approximately 3-4 hours. Participants need to keep stable medications and rehabilitation routines during this time. * Follow-up (10 Weeks) Participants will undergo follow-up assessments at the end of treatment and 10 weeks after treatment. Assessments include clinical scales, MRI, and EEG.

Efficacy of Repetitive Transcranial Magnetic Stimulation for Improving Depressive Symptoms in Patients With Parkinson's Disease

The purpose of this study is to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving depressive symptoms in patients with Parkinson's Disease (PD). Participants will be randomly assigned to either an active rTMS group or a sham-control group. The study aims to establish an optimal treatment protocol using a neuronavigation system and to validate treatment responses through various digital biomarkers such as facial expression analysis and eye-tracking.

A Study to Evaluate the Efficacy and Safety of Intravenous (IV) Prasinezumab in Participants With Early-Stage Parkinson's Disease

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics (PK) of prasinezumab compared with placebo in participants with early-stage Parkinson's disease (PD) on stable symptomatic monotherapy with levodopa.

Exenatide Once Weekly Over 2 Years as a Potential Disease Modifying Treatment for Parkinson's Disease

This study is a clinical trial in patients with Parkinson's disease (PD), of a drug called exenatide, which is already licensed for the treatment of patients with type 2 diabetes. There have been several groups that have confirmed that exenatide has beneficial effects of nerve cells when tested in the laboratory, which raises the possibility that exenatide may slow down or stop the degeneration of PD. In an open label trial in patients with PD who self administered the drug for a period of 48 weeks, the investigators have previously shown that the drug is well tolerated and shows encouraging effects on the movement and non-movement aspects of the disease. A double blind placebo controlled trial involving 60 participants was then conducted which indicated that exenatide may be a "neuroprotective" drug, i.e. one that stops the nerve cells dying in PD. The next step is therefore to confirm this "neuroprotective" effect and to see whether this effect can be reproduced in a multi-centre setting including a larger number of participants. An important objective is to explore whether any positive effects remain static or increase when the treatment is continued over a 96 week period. In order to explore this, a randomised, double blind, parallel group, placebo controlled, Phase 3 trial of Exenatide is being undertaken (Exenatide-PD3).

Deep Brain Stimulation Therapy in Movement Disorders

Background: \- In deep brain stimulation (DBS), a device called a neurostimulator is placed in the chest. It is attached to wires in parts of the brain that affect movement. DBS might help people with movement disorders like Parkinson s disease (PD), dystonia, and essential tremor (ET). Objective: \- To provide DBS treatment to people with some movement disorders. Eligibility: \- Adults 18 years and older with PD, ET, or certain forms of dystonia. Design: * Participants will be screened with medical history and physical exam. They will have blood and urine tests and: * MRI brain scan. The participant will lie on a table that slides in and out of a metal cylinder with a magnetic field. They will be in the scanner about 60 minutes. They will get earplugs for the loud noises. During part of the MRI, a needle will guide a thin plastic tube into an arm vein and a dye will be injected. * Electrocardiogram. Metal disks or sticky pads will be placed on the chest, arms, and legs. They record heart activity. * Chest X-ray. * Tests of memory, attention, concentration, thinking, and movement. * Eligible participants will have DBS surgery. The surgery and hospital care afterward are NOT part of this protocol. * Study doctors will see participants 3 4 weeks after surgery to turn on the neurostimulator. * Participants will return every month for 3 months, then every 3 months during the first year, and every 6 months during the second year. Each time, participants will be examined and answer questions. DBS placement will be evaluated with MRI. The neurostimulator will be programmed. At two visits, participants will have tests of movements, thinking, and memory.

Auditory Sleep Stimulation or Sham in People With Parkinson Disease Mild Cognitive Impairment During Cognitive Training

People with Parkinson's disease are at higher risk of cognitive decline, and current treatments cannot fully prevent this. This study explores non-drug ways to support brain function. Intervention: Participants will complete a 5-week cognitive training program at home ("brain fitness"). In addition, they will use a sleep device at night that plays soft sounds to improve deep sleep; Half of the participants will actually receive these sounds (auditory stimulation), while the other half will receive a sham (placebo) version - neither the participants nor the researchers will know the group assignment. Assessments will take place before and after the intervention, and again three months later, including one overnight stay at University Hospital Zurich per assessment. The goal is to find out whether improving deep sleep can boost the benefits of cognitive training and help slow cognitive decline in Parkinson's disease.

Clinical Laboratory Evaluation of Chronic Autonomic Failure

Background: The autonomic nervous system controls automatic body functions. Researchers want to improve the tests used to diagnose autonomic failure. Orthostatic hypertension is a drop in blood pressure when a person stands up. Researchers want to focus on this sign of autonomic failure. Objective: To improve testing for conditions that cause autonomic nervous system failure. Eligibility: People ages 18 and older in one of these categories: * Their blood pressure drops when they get up. * They have had a heart transplant or bilateral endoscopic thoracic sympathectomies or have had or will have renal sympathetic ablation Design: All participants will be screened with: * Medical history * Physical exam * Blood and urine tests Some participants will be screened with: * Heart and breathing tests * IV placement into an arm vein * Tilt table testing: Participants lie on a table that tilts while an IV is used to draw their blood. Participants may stay in the hospital for up to 1 week depending on their tests. Tests may include repeats of screening tests and: * Sweat testing: A drug is placed on the skin to cause sweating. Sensors on the skin measure moisture. * Lumbar puncture: A needle is inserted between the bones in the back to collect fluid. * MRI and PET/CT scan: Participants lie on a table that slides into a scanner. For the PET/CT, a small amount of a radioactive chemical will be injected with a small amount of a radioactive chemical. * Bladder catheter placement to collect urine * Skin biopsies: A punch tool removes a small skin sample. * Tests to see how the pupils react to light * Smelling tests * Thinking and memory tests * Questionnaires Participants may have a visit about 2 years later to repeat tests.

Patterned Multichannel Vibrotactile Stimulation for the Longitudinal Treatment of Moderate Stage Parkinson's Disease

The purpose of the present research is to examine the effectiveness of a non-invasive, vibrotactile stimulation protocol, known as coordinated reset (CR), for the alleviation of motor symptoms in patients with Parkinson's disease (PD). PD patients exhibit rigidity, slowness (bradykinesia) and poverty (akinesia) of movement as well as other symptoms. Treatment for PD is either pharmacological (first line) or invasive deep brain stimulation. The non-invasive, vibrotactile stimulation approach uses a novel stimulation pattern to disrupt the pathophysiological mechanism that is responsible for PD symptoms and thus restore motor function.

PET Imaging of Cyclooxygenases in Neurodegenerative Brain Disease

Background: About 5 million adults in the U.S. have Alzheimer s disease or another adult-onset neurodegenerative disorder. Many studies have found that inflammation in the brain contributes to these diseases. Researchers want to find a better way to measure this inflammation. Objective: To learn whether COX-1 and/or COX-2 is elevated in the brains of individuals with neurodegenerative brain disease compared to healthy volunteers. Eligibility: Adults age 18 years and older in good general health who have an adult-onset neurodegenerative dementia, such as AD, FTD, corticobasal syndrome, Huntington s disease, or MCI, ALS and healthy adult volunteers enrolled in protocols 01-M-0254 or 17-M-0181. Design: Participants will be screened with medical history, physical exam with vital signs, and lab tests. They will have a neuropsychological testing. Their heart function will be measured. Participants will have a magnetic resonance imaging (MRI) scan. The MRI scanner is a metal tube surrounded by a strong magnetic field. Participants will lie on a table that slides in and out of the tube. The machine makes noise. Participants will get earplugs. Participants will have 2 PET scans. They will be injected with the study drugs through an intravenous catheter placed in an arm vein. The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and out of the scanner. A plastic mask will be molded to their head to keep them from moving. A thin plastic tube will be put into an artery at the wrist or elbow crease area. This will be used to draw blood during the scan. Participants will have 2-5 study visits. Participation lasts 1 week to 4 months, depending on scheduling.