Clinical Research Directory

Anesthesia and Postoperative Delirium in Parkinson DBS

Parkinson's disease (PD) is the second most common neurodegenerative disorder, with a rising incidence due to global aging. Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is a core therapeutic modality for motor symptoms in patients with moderate-to-advanced PD. However, Postoperative Delirium (POD) is a common and significant complication following DBS surgery, affecting up to 42.6% of patients. POD is associated with prolonged hospitalization, increased medical costs, and poorer neurological prognosis. Current evidence regarding the incidence of POD after STN-DBS and the impact of different anesthesia management strategies remains limited, with a lack of large-scale prospective studies. This study aims to prospectively investigate the incidence, risk factors, and anesthesia-related neuroprotective mechanisms of POD in PD patients undergoing STN-DBS. Specifically, the study seeks to: Determine the incidence of POD within 3 days postoperatively. Analyze the correlation between anesthesia management (including anesthetic agents, depth, and hemodynamics) and the occurrence of POD. Explore the interaction between POD and postoperative non-motor symptoms such as pain, sleep disturbances, and long-term cognitive function. Construct a multidimensional prediction model for POD based on preoperative and intra-operative data.

Wearable for Assessing Tremor and Continuous Health in Parkinson's and Essential Tremor Diseases

This prospective observational study will examine tremor and upper-limb movement in adults with Parkinson's disease or Essential Tremor using non-invasive wearable sensors. Participants will attend one clinic visit and may then wear sensors at home for 3, 7, or 21 days. Clinic assessments will be scheduled around participants' usual medication times; the study will not change or delay treatment. Sensor data will be analysed offline for research and will not be used to make clinical decisions.

Effects of Tai Chi Therapy Versus Qi-Gong in Stage-I Parkinson's Patients.

This study has important clinical, academic, and practical relevance in neuromuscular rehabilitation. Clinically, it aims to identify effective and tolerable rehabilitation strategies for individuals with Parkinson's disease by comparing Tai Chi Therapy with Qi-Gong there by supporting evidence-based physiotherapy practice and improving patient adherence. Academically, it contributes to the limited literature on comparative effectiveness of these interventions and incorporates patient-centered outcomes such as exercise perception, which are often underreported. From a practical and societal perspective, identifying a more acceptable and effective approach may enhance long-term participation in rehabilitation, potentially slow disease progression, and reduce the overall healthcare burden associated with Parkinson's disease.

The Role of METhanogens in the PROgression Of Parkinson's Disease and Related Neurological Conditions

Gut problems, such as constipation, can have an important impact on quality of life of people who have them, and have been associated with higher risk of developing neurological diseases such as Parkinson's or Alzheimer's disease. Recent studies suggest that gut problems may also have implications for the progression of these diseases, as constipation is a risk factor for faster Parkinson's and Alzheimer's progression. However, how constipation and brain diseases are linked is unknown. Previous research has suggested that gut changes may lead to inflammation, which could play a role in accelerating the progression of both movement and memory problems in Parkinson's and memory and thinking problems in people with cognitive impairment. Methane is a gas that is naturally produced by microorganisms in the gut. Levels of methane can be measured using a simple breath test. Higher methane levels in the breath are thought to be more common in people with Parkinson's disease (PwP) when compared to people without Parkinson's (healthy controls) and have been associated with gut symptoms, particularly constipation, as well as worse movement problems in PwP, although they are less understood in conditions that affect memory and thinking (like dementia or mild cognitive impairment). The investigators want to better understand the changes in the gut of PwP and people with cognitive impairment (e.g. mild cognitive impairment or dementia). They will compare breath methane levels in PwP, people with cognitive impairment, people with REM Sleep Behaviour Disorder (a sleep condition linked to a higher risk of developing Parkinson's) and healthy participants. Participants will be followed-up over time to assess how methane levels are linked to changes in the blood and the stools, gut function, and clinical symptoms. This study has 2 components: Component 1: observational study, where the study investigators will follow 200 participants over 2 visits, 18 months apart. The study will recruit 4 groups of people: 50 people with Parkinson's disease, 50 people at high risk of developing Parkinson's disease (people with REM Sleep behaviour disorder), 50 people with other conditions affecting cognition (e.g. dementia, mild cognitive impairment), and 50 healthy controls. Component 2: study with 15 people with Parkinson's, who produce high methane levels, to test whether a probiotic (Lactobacillus reuteri) affects how much methane is produced.

Characterization and Validation of the Short Physical Performance Battery in Individuals Diagnosed With Parkinson's Disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with motor and non-motor impairments that affect physical function, mobility, balance, and quality of life. Although Galicia is one of the Spanish regions with a high prevalence of PD, comprehensive information regarding the functional characteristics of this population remains limited. This observational cross-sectional study aims to characterize the sociodemographic, clinical, cognitive, behavioral, and functional profile of individuals with Parkinson's disease in Galicia and to evaluate the validity and reliability of the Short Physical Performance Battery (SPPB) in this population. The findings will provide updated information on the functional status of people with PD in Galicia and support the use of the SPPB as a practical tool for the assessment of physical performance in clinical and research settings.

GBPDC: Gut-Brain in PD Consortium Master Protocol

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).

Home-Based Exercise Programs for Fall Prevention in Parkinson Disease

Falls are common in patients with Parkinson disease and may lead to reduced mobility, fear of falling, loss of independence, and injury. Exercise-based rehabilitation programs may help improve balance, gait, and physical performance in this population. This randomized controlled trial aims to compare the effectiveness of two home-based exercise programs in patients with Parkinson disease: the Otago Exercise Program and a structured home exercise program. Participants will be randomly assigned to one of two groups. Both groups will receive exercise education and will perform their assigned home exercise program for 6 weeks. Participants will be evaluated at baseline, at week 3, and at the end of week 6. The study will assess fall-related outcomes, freezing of gait, functional mobility, gait parameters, postural control, and physical performance. The results may help determine which home-based exercise approach is more effective for reducing fall risk and improving functional outcomes in patients with Parkinson disease.

Safinamide vs Placebo for Pain in Patients With Parkinson's Disease and Motor Fluctuations

This is a Phase III, single-center, randomized, double-blind, placebo-controlled clinical trial designed to investigate the superiority of safinamide compared to a placebo in reducing Parkinson's Disease (PD)-related pain. The trial plans to enroll 60 adult patients diagnosed with PD who experience motor fluctuations and chronic pain (lasting more than 3 months) despite receiving stable doses of levodopa. Participants will be randomized in a 1:1 ratio to receive either oral safinamide or a matching placebo as an add-on therapy. The treatment regimen consists of 50 mg/day for the first week, increasing to 100 mg/day for the remaining 11 weeks, for a total treatment duration of 12 weeks. The primary endpoint is to evaluate the mean change in pain severity from baseline to 12 weeks, measured using the 11-point Numeric Rating Scale (NRS) Secondary endpoints will assess additional qualitative and quantitative pain characteristics (KPPS, BPI, PD-PCS), motor symptoms and treatment complications (UPDRS Parts III and IV, Home Diary), quality of life (PDQ-39), and other non-motor symptoms (MDS-NMS). The total expected duration of the clinical trial is 24 months.

Remotely Supervised Home-based Transcranial Temporal Interference Stimulation on Motor Symptoms in Parkinson's Disease

The goal of this clinical trial is to learn if home-based temporal interference stimulation (TIS) works to improve motor symptoms in people with Parkinson's disease (PD). It will also learn about the safety of this treatment. The main questions it aims to answer are: 1. Does home-based TIS improve movement problems such as slow movement, stiffness, and walking difficulty? 2. Are the effects maintained after the treatment ends? 3. What medical problems (adverse events) occur during treatment? Researchers will compare active TIS to a sham treatment (a look-alike procedure that does not deliver active stimulation) to see if TIS works. Participants will: 1. Receive active TIS or sham stimulation once a day for 4 weeks at home under remote supervision 2. Visit the clinic at specific time points for movement assessments 3. Complete online questionnaires about symptoms and quality of life

Objective Longitudinal Assessment of Postural Stability and Gait of Stroke, Parkinson's Disease and Multiple Sclerosis Using Instrumented Posturography and Three Dimensional Motion Analysis

Nowadays, stroke is one of the most common leading causes of death in many countries. As the number of stroke patients is increasing, even in younger age groups, there is an increasing need to improve their rehabilitation. In order for this process to start, it is inevitable to integrate the latest recommendations of health and sports science into rehabilitation, in addition to medicine, so that the treatment is as complex as possible. Parkinson's disease is one of the most common neurological diseases, in addition to stroke. The most significant damage can be experienced in motor functions, since one of the main symptoms of the disease is slowed movement, tremor and balance disorders. This postural change can lead to many other musculoskeletal changes, which is why Parkinson's disease is an extremely complex disease that also requires a complex treatment. The third disease examined in our research is multiple sclerosis (MS), which is also one of the most significant nervous system diseases, with nearly 1 million cases registered so far. The most common symptoms of MS patients are weakness, numbness, dizziness, coordination and balance disorders, as well as changes and uncertainty in the gait pattern. One of the essential foundations of rehabilitation after neurological diseases is neurorehabilitation, since the process will only be truly effective if cognitive and motor functions are developed in parallel. In the case of neurological diseases, as we can see above, one of the most significant symptoms is coordination and balance disorders. When the nervous system is affected, trunk control and the patient's posture will always change, depending on the given disease and the individual. One of the fundamental goals of rehabilitation should be to develop stability and postural control, because without these, we will not be able to effectively develop and restore the patients' significant motor functions. This is why it is important that neurological patients are assessed from this perspective as early as possible, so that their treatment plan can be adapted to their disease and themselves as much as possible.

Gut Microbiota and Tryptophan Metabolites in Parkinson's Disease

Parkinson's disease is a progressive neurological disorder that can also affect the digestive system. Changes in gut microorganisms and tryptophan metabolites may be associated with Parkinson's disease, but these relationships are not fully understood. This exploratory observational study will compare gut microbial communities and targeted tryptophan metabolite profiles between 15 participants with Parkinson's disease and 15 healthy controls matched by sex, age, and body mass index. Each participant will provide clinical and lifestyle information and one stool sample. Stool samples will be analyzed using 16S ribosomal RNA gene sequencing and targeted liquid chromatography-tandem mass spectrometry. The study will evaluate differences in gut microbial composition and selected tryptophan metabolites and explore their associations with constipation, bowel habits, medication use, and clinical features of Parkinson's disease. No treatment will be assigned, and participants' usual medical care will not be changed. The findings are exploratory and are intended to guide larger future studies; they cannot establish causality or be used to diagnose Parkinson's disease.

Prescriptive Infusion Algorithm (PIA)

This study is being done to test a new way of delivering AB-1005 into the brain. The goal is to make the procedure easier and quicker to perform, while providing similar amounts of drug to the part of the brain that needs treatment. Technical (Stage 0) To test if the new delivery method (prefrontal surgical approach) can consistently deliver AB-1005 to the putamen using MRI monitoring. Technical (Stage 1) To test if the new delivery method (PIA-based infusion) can consistently deliver AB-1005 to the putamen using brain imaging by MRI. Technical (Stage 2) To confirm the new delivery method works without brain imaging by MRI, using standard operating room tools including brain imaging by CT. Safety (Stage 1 and 2) To assess the safety and tolerability of the new delivery method for AB-1005 up to 6 months after surgery

Investigating the Increased Risk of Falls in Individuals With Parkinson's Disease Treated With Deep Brain Stimulation

The purpose of this pilot study is to assess changes in thinking and movement after deep brain stimulator implantation. The study will also examine whether these changes are related to the risk of falls.

Effect of Hand Rehabilitation on Cognitive Function in Patients With PD

Evidence suggests the association between fine motor skills of the hand and cognitive function, as well as the positive effects of hand rehabilitation on hand function and the effectiveness of cognitive rehabilitation on cognitive functions in patients with Parkinson's disease (PD). In response to the question of whether there is a cause-and-effect relationship between fine manual skills and cognitive function, we designed the present randomized controlled trial to investigate the effectiveness of sensory-motor rehabilitation of the hand on cognitive functions compared to the effectiveness of cognitive rehabilitation on sensory-motor skills of the hand in patients with PD. In this double-blinded, randomized controlled trial, a convenience sample including 48 people with PD will participate based on simple non-random sampling. The participants will be allocated randomly through stratified randomization to parallel groups of intervention (sensorimotor hand rehabilitation) and control (cognitive rehabilitation) with a 1:1 allocation ratio. The associate researcher responsible for assessing outcome measures and the statistician responsible for analyzing the data are blinded to the intervention protocol. The intervention protocol for the intervention group includes hand sensory-motor rehabilitation for 10 one-and-a-half-hour sessions, 3 sessions per week, in addition to cognitive rehabilitation for 10 one-and-a-half-hour sessions, 3 sessions per week. The intervention protocol for the control group includes cognitive rehabilitation for 10 one-and-a-half-hour sessions, 3 sessions per week. All participants undergo three assessment sessions: the day before the intervention, the day after the intervention, and one month after the last intervention session. Data will be analyzed using SPSS version 22.0. The significance level will be set at 0.05.

Multicontext Approach for Cognitive Function in Parkinson Disease

Mild cognitive decline is common in early Parkinson disease (PD) and is associated with disability, reduced quality of life (QOL), and increased risk for dementia. Medical treatments for PD do not prevent or treat cognitive decline and may even exacerbate the problem. Unfortunately, existing cognitive interventions for PD, which focus on restoring deficient cognitive skills through cognitive training (repetitive practice of tasks that challenge specific cognitive skills), provide limited benefit for daily function and QOL. To overcome this limitation, the investigators use strategy training. the investigators help people develop targeted strategies to use in everyday life to circumvent cognitive deficits and accomplish daily activities. Contemporary cognitive rehabilitation evidence supports strategy training for other neurological conditions and mild cognitive impairment (MCI), but it has not been well-studied in PD. By teaching strategies for everyday cognition, the investigators hypothesize that our interventions will improve functional outcomes for people with PD. Study participants will complete a baseline cognitive testing session, 10 cognitive treatment sessions with a trained occupational therapist, then have follow-up visits with the study team at 1-week, 3-months, 6-months, and 12-months after completing the study intervention.

Mental Imagery on Upper Extremity Skills

Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized pathologically by the progressive loss of dopaminergic neurons in the substantia nigra and clinically by the presence of motor symptoms such as bradykinesia, resting tremor, and/or rigidity. Among the motor deficits frequently observed in PD, patients are known to frequently report difficulties with manual dexterity. Many upper extremity and manual dexterity deficits are present in PD. Motor imagery (MI) is the imaginal execution of motor activities or the activation of specific muscles in the absence of any explicit feedback. This area of rehabilitation has been shown to be effective in improving and developing motor skills in many neurological conditions where patients exhibit motor recognition and execution impairments. MI can be applied at all stages of recovery from PD, is highly effective in movement-related pathologies, and can be performed independently.There is sufficient evidence that MI improves motor performance and learning in individuals with neurological disorders such as multiple sclerosis, stroke, and spinal cord injury. The study was designed to investigate the immediate effects of mental imagery, which is thought to be effective in controlling difficulties in planning and initiating movements in PD, on upper extremity skills. Therefore, the aim of this study was to determine the effect of mental imagery on upper extremity skills in PD.

SwallowFIT Study in Parkinson's Disease

The goal of this clinical trial is to learn if a proactive swallow exercise will help to improve swallow fitness in patients with Parkinson's disease. The aim of the study is to assess how effective this exercise is and to measure the change in swallowing fitness from the beginning to the end of the study. Patients who are given the exercise training will be compared to participants who are treated using the usual standard treatment. Patients will have 6 weeks of twice-weekly SwallowFIT training. Each session will be an hour long.

Intestinal Levodopa + Entacapone Therapy (Lecigon®) to Counteract Dopaminergic Desensitization and Neuropsychiatric Complications in Parkinson's Disease

This study is a Phase III multicentric randomized controlled trial with parallel group design and waiting list in patients that have an indication to undergo intestinal L-Dopa + entacapone (Lecigon®) under the existing indication criteria (according to SmPC (Fachinformation) Lecigon®). As primary endpoint, we will analyze the difference of the pre-interventional baseline and 6-month follow-up on the "hyperdopaminergic symptoms" corresponding to section 3 of the "Ardouin Behavioural Scale" hypothesizing on the superiority of LECIG therapy compared to best medical treatment.

Which Tools Better Predict Fall Risk in Parkinson's Disease: A Comparative Study of Objective, Self-Reported, and Functional Balance Assessment

Introduction: Falls are common in Parkinson's disease (PD), affecting 30-90% of patients annually, with more than half experiencing recurrent falls. Identifying balance assessment tools that are both practical and predictive of fall risk is therefore essential. This study aimed to investigate the relationship between fall frequency and three balance assessment tools: the Biodex Balance System (objective), the Falls Efficacy Scale-International (FES-I) (self-reported), and the Mini-Balance Evaluation Systems Test (Mini-BESTest) (functional). Methods: Patients with PD at Hoehn and Yahr stages 1-3 will be included in the study. Fall data will be collected using a fall diary, while objective balance will be assessed with the Biodex Balance System, functional performance will be evaluated with the Mini-BESTest, and self-reported balance confidence will be measured with the FES-I.

Protocol of the Packer Managing Fatigue Program Versus Standard Information to Improve Energy Conservation Self-Efficacy in Parkinson's Disease

This protocol describes a randomized, controlled, parallel-group, trial evaluating the effectiveness of a group-based fatigue management program for people with Parkinson's disease. The study will be conducted in Italy, with participant recruitment planned to begin on July 1st, 2025. The primary sponsor is the Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health (DINOGMI) at the University of Genoa, Italy. No external sources of monetary or material support have been declared. The study has received ethical approval from the University of Genoa's Research Ethics Committee (Comitato Etico per la Ricerca di Ateneo - CERA), under protocol number 2025.36, approved on April 3rd, 2025. The scientific title of the trial is: Protocol for a Superiority Randomized Controlled Trial of a Group-Based Fatigue Management Program Versus Standard Information to Improve Self-Efficacy in Energy Conservation in Parkinson's Disease". The public title is: "Energy Matters: A Protocol of a Randomized Controlled Trial of a Group-Based Fatigue Management Program for People with Parkinson's Disease". The study targets individuals diagnosed with idiopathic Parkinson's disease, experiencing fatigue. Eligible participants must be over 18 years old, present with Hoehn and Yahr stage ≤3.5, and score ≥4 on the Fatigue Severity Scale (FSS). Exclusion criteria include a Montreal Cognitive Assessment (MOCA) score below 22, presence of severe psychiatric comorbidities, medical conditions contributing independently to fatigue, inability to participate in group sessions, or involvement in other structured fatigue management programs. Participants will be randomly allocated to one of two arms. The intervention group will attend a six-week Packer Managing Fatigue Program1 Sessions will be conducted in groups of 8-10 participants, led by a licensed occupational therapist. Topics covered include rest, communication, body mechanics, ergonomics, energy-conserving tools, prioritization, lifestyle balance, and goal setting. Sessions will use standardized materials such as participant workbooks2 and visual aids and will take place in appropriately equipped rooms. If a participant is absent from a scheduled group session for personal reasons, the occupational therapist will organize an individual make-up session before the next scheduled group session. This individual session will follow the same content and structure as the missed group session, based on the Packer Managing Fatigue Program. Its purpose is to ensure continuity and fidelity to the intervention, and to allow participants to stay aligned with the group program. Participants in the control group will be provided with six fact sheets addressing general information about Parkinson's disease and fatigue. The primary outcome is the change in self-efficacy for performing energy conservation strategies, measured using the Self-Efficacy for Performing Energy Conservation Strategies Assessment (SEPECSA), assessed at baseline, post-intervention, and at a 3-month follow-up. Secondary outcomes include measures of motor and non-motor symptoms (Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I and II), fatigue severity (Fatigue Severity Scale, Parkinson Fatigue Scale), Fatigue Impact (Modified Fatigue Impact Scale), quality of life (Parkinson Disease Questionnaire-39), participation and autonomy (Impact on Participation and Autonomy questionnaire), psychiatric symptoms (Hospital Anxiety and Depression Scale), occupational balance (Occupational Balance Questionnaire-11) and sleep disturbance (Pittsburgh Sleep Quality Index - PSQI). All outcomes will be reassessed immediately and 3 months after the end of the intervention. The total planned sample size is 74 participants, with 37 individuals in each study arm. For public queries, the contact person is Dr. Elisa Pelosin, Associate Professor at DINOGMI, University of Genoa (email: elisa.pelosin@unige.it). For scientific queries, the reference contact is the University of Genoa's Ethics Committee (email: presidente.cera@unige.it). An individual participant data sharing plan is in place. As part of the informed consent process, participants will be asked whether they agree to allow their anonymized data to be shared for future research purposes. Only data from participants who provide explicit consent will be shared. Anonymized individual data will be made available upon reasonable request, in accordance with institutional policies and data protection regulations. Access will be granted by the corresponding author after publication and will remain open for five years

Treatment of Cognitive and Sensorimotor Deficits in Parkinson's Disease With High Definition Transcranial Direct Current Stimulation

The purpose of this research study is to examine the effects of transcranial Direct Current Stimulation (tDCS) on verbal retrieval and cognition and sensorimotor control and to determine if tDCS can be used as a way to improve retrieval, sensory, and motor abilities in individuals with Parkinson's disease (PD).

Cognitive-Based Balance Rehabilitation in Parkinson's Disease: Virtual Reality vs. Dual Task

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.

A Clinical Study to Evaluate the Safety of MF1, a New Treatment for Parkinson's Disease-related Disorders (MF1 Study)

This is a Phase I, investigator-initiated, first-in-human study to evaluate the safety, tolerability, and pharmacokinetics of MF1, a novel agent that is expected to inhibit α-synuclein related pathogenesis in α-synucleinopathies, primarily Parkinson's disease (PD). MF1 aims to address the unmet medical need in PD, which affects about 1% of individuals aged 60 years and older in Japan and is projected to reach 43 million patients worldwide by 2050. The trial consists of three parts: Part A (single ascending dose) and Part B (multiple ascending dose) in healthy Japanese male adults, and Part C (multiple dose) in patients with idiopathic PD. Part A is a randomized, double-blind, placebo-controlled, single-center study assessing single oral doses , including a food-effect evaluation. Part B is a randomized, double-blind, placebo-controlled, single-center study with once-daily dosing for 7 days. Part C is an open-label, multicenter study in 4-8 PD patients (MDS 2015 criteria, Hoehn \& Yahr stage ≤3) receiving once daily for 14 days, with or without stable background antiparkinsonian therapy. The primary objective is to assess safety and tolerability; secondary objectives include characterization of plasma, urine, and cerebrospinal fluid pharmacokinetics and assessment of food effect. Exploratory pharmacodynamic endpoints include biomarkers such as α-synuclein, neurofilament light chain, UCHL-1, FABP3, GFAP, and other neurodegeneration markers. Key exclusion criteria include clinically significant systemic diseases, seizure history, serious infections (HBV, HCV, HIV, syphilis), recent suicidal ideation or attempts, and recent use of other investigational products.

Effects of Accelerated rTMS On Motor and Cognitive Function in Parkinson's Disease

Parkinson's disease (PD) is a brain disorder that causes progressive problems with movement, such as slowness, stiffness, tremor, and difficulty walking. Many people with PD also develop problems with thinking and memory. Current medications can help control movement symptoms but often become less effective over time and may cause side effects. There is a need for additional treatment options that can address both movement and thinking difficulties in PD. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive treatment that uses magnetic pulses delivered to the scalp to stimulate specific areas of the brain. Previous research has shown that rTMS targeting the motor cortex (the part of the brain that controls movement) can improve motor symptoms in people with PD. The purpose of this pilot study is to evaluate whether an accelerated course of rTMS targeting the motor cortex can improve movement and thinking abilities in people with mild to moderate Parkinson's disease. The study will enroll 40 participants aged 50 to 90 years at the San Francisco Neurology and Sleep Center. Participants will receive 6 sessions of rTMS using the EXOMIND™ device, administered twice per week over approximately 3 weeks. Each session delivers high-frequency magnetic stimulation to the motor cortex on both sides of the brain. Participants will be assessed before treatment, at the last treatment session, and at 1-month and 3-month follow-up visits. The primary outcome measure is the change in motor symptoms as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) at 1 month after treatment. Secondary outcomes include additional measures of walking and gait, domain-specific cognitive testing using the Creyos cognitive battery (assessing memory, attention, reasoning, and other thinking skills), the Montreal Cognitive Assessment (MoCA), depression symptoms (PHQ-9), and quality of life (PDQ-39). This is a single-center, open-label study with no placebo or control group. Total participation duration is up to 139 days, including screening, treatment, and follow-up visits.