Clinical Research Directory

Udall Project 1 Aim 4

By defining the strength and direction of connectivity patterns at rest and during movement across the basal ganglia-thalamocortical (BGTC) network we will characterize the role of individual circuits in motor performance and cognitive function, paving the way for future development of optimization algorithms for DBS that take advantage of this understanding.

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.

Testing of an Interface for Synchronizing tACS-DBS With a Phase-locked-loop

The investigators aim to test an interface to phase-lock transcranial alternating current stimulation (tACS) and deep brain stimulation (DBS) for future studies investigating the effects of different time-lags between DBS and tACS on the behavioural and neural level. To test if the interface works in patients with DBS, the investigators record EEG during synchronized tACS-DBS in several patients. The investigators hypothesize that they can apply tACS at the desired phase-lags relative to DBS pulses and confirm this with EEG measurements of the DBS and tACS artifact.

A Multicenter Pediatric Deep Brain Stimulation Registry

There is limited data on outcomes for children who have undergone deep brain stimulation (DBS) for movement disorders, and individual centers performing this surgery often lack sufficient cases to power research studies adequately. This study aims to develop a multicenter pediatric DBS registry that allows multiple sites to share clinical pediatric DBS data. The primary goals are to enable large-scale, well-powered analyses of the safety and efficacy of DBS in the pediatric population and to further explore and refine DBS as a therapeutic option for children with dystonia and other hyperkinetic movement disorders. Given the current scarcity of evidence available to clinicians, this centralized multicenter repository of clinical data is critical for addressing key research questions and improving clinical practice for pediatric DBS.

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.

Sleep-specific DBS Therapy in Parkinson's Disease

Sleep-wake disturbances are a major factor associated with reduced quality of life of individuals with Parkinson's disease (PD), a progressive neurological disorder affecting millions of people in the U.S and worldwide. The brain mechanisms underlying these sleep disorders, and the effects of therapeutic interventions such as deep brain stimulation on sleep-related neuronal activity and sleep behavior, are not well understood. Results from this study will provide a better understanding of the brain circuitry involved in disordered sleep in PD and inform the development of targeted therapeutic interventions to treat sleep disorders in people with neurodegenerative disease.

Neural Mechanisms of Aerobic Exercise Benefits in PD With DBS

This study is focused on people with Parkinson's disease who already have deep brain stimulation devices. The goal is to understand how aerobic exercise, specifically forced vs voluntary cycling, affects movement, thinking, and brain activity in these individuals. Parkinson's disease is a progressive condition that impacts both movement and cognitive function. Previous research suggests aerobic exercise can improve PD symptoms, but the mechanisms underlying the improvement are not fully understood. This study aims to evaluate the neural (brain) mechanisms underlying exercise.

Use of CereGate Therapy for Freezing of Gait in PD

A Multi-Center, Controlled Study to Evaluate Use of CereGate Therapy to Reduce Freezing of Gait in Participants Diagnosed with Parkinson's Disease.

Predictors of Clinical Outcomes of Deep Brain Stimulation in Parkinson's Disease

The goal of this observational study is to identify factors in blood that are associated with response to deep brain stimulation (DBS) surgery in patients with Parkinson's disease. The main questions it aims to answer are: 1. What factors in blood (proteins and RNA) are associated with good vs poor response to DBS? 2. Are these factors able to predict response to DBS? 3. How do these factors change before and after DBS? Blood and leftover brain tissue (which spontaneously adhere to the surgical instruments) will be taken and routine clinical data (including scores from routine assessments) will be collected from consenting participants who undergo DBS.

LIFUS For Neurological Disorders

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.

Safety and Tolerability of Patterned Stimulation for DBS in the Home Setting

The primary objective of the proposed pilot study is to assess the safety and tolerability of active patterned Deep Brain Stimulation (pDBS) when administered in a home setting for patients with Parkinson's disease (PD) who have had stable bilateral Subthalamic Nucleus (STN) and Globus Pallidus internus (GPi) DBS.

Adaptive vs. Continuous Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease

The objective of the CLOSE-PD study is to compare the efficacy of adaptive deep brain stimulation (aDBS) with continue deep brain stimulation (cDBS) in patients with Parkinson's disease. The main question it aims to answer is: \- whether the change in daily mean ON time without troublesome dyskinesia in aDBS is greater than cDBS over a six-month follow-up period? Researchers will compare aDBS to regular continue deep brain stimulation (cDBS). Participants will: * be set up to cDBS during the first programming visit (visit 2); * be randomized 1:1 to aDBS or cDBS two weeks after visit 2; * follow-up will be at three and six months after visit 2; * complete PD Home diary at baseline, two weeks, three months and at six months after visit 2.

Comparing Biomarker-Guided DBS Programming With Standard Clinical Monopolar Programming

The goal of this clinical trial is to learn whether an objective, data-guided approach to programming deep brain stimulation (DBS) can improve motor outcomes in people with Parkinson's disease who undergo DBS surgery. The study includes adults aged 30 to 70 years with Parkinson's disease who are candidates for DBS. The main questions it aims to answer are: Does DBS programming based on objective markers (brain imaging and brain signals) reduce the amount of daily time patients spend in the OFF state more than conventional clinical programming? Does this programming approach improve quality of life and motor symptoms compared with standard programming? Researchers will compare conventional DBS programming based on clinical monopolar review with DBS programming guided by electrode location on neuroimaging and beta brain signals recorded from the implanted device, to see if the objective approach leads to better motor control and less OFF time. Participants will: Undergo DBS surgery using a clinically approved DBS system Be randomly assigned to one of two DBS programming strategies Wear inertial sensors at home for several days at different time points to objectively measure motor symptoms Attend scheduled clinical visits for DBS programming and motor and non-motor assessments Have adaptive DBS activated after 3 months and continue follow-up until 6 months after programming begins

Enhancing Gait Using Alternating-Frequency DBS in Parkinson Disease

The purpose of this study is to assess how alternating-frequency Deep Brain Stimulation (DBS) works to improve postural instability and gait, while also treating other motor symptoms of Parkinson Disease (PD).

Quantifying Motor Network Dynamics to Predict and Enhance Outcomes in Pediatric Dystonia

The goal of this study is to understand the development and progression of childhood dystonia, a movement disorder, in children. The main questions it aims to answer are: How does the activity of the neural network evolve in children with dystonia in the context of motor development? What are the effects of chronic and active stimulation on cortical and subcortical motor network function in children with deep brain stimulation (DBS)? Participants will: * Undergo noninvasive electrophysiological measurements (EEG, EMG) to quantify neural network activity. They will be tested at rest and during a simple motor reaction task. * Children with DBS will be assessed in the on and off DBS state to assess effects of chronic and active changes in motor network function.

Revision of Deep Brain Stimulator in Patients With Parkinson's Disease

Parkinson's disease is a chronic and progressive neurodegenerative disease that affects the central nervous system, particularly impairing movement control. It is associated with the loss of dopamine-producing cells in the brain and typically occurs in middle age and beyond. Deep brain stimulation (DBS) is considered when symptoms of Parkinson's disease, such as tremors, slowed movements, and muscle rigidity, are not adequately controlled with medications. Selected patients with severe symptoms that do not respond to medical treatment are generally considered for this treatment. Battery revision surgeries can be performed under general anesthesia or regional anesthesia. Patients undergoing general anesthesia should be cautious about the potential complications of general anesthesia, while those undergoing regional anesthesia should be cautious about the local anesthetic systemic toxicity. Because each method has its own advantages, the choice of anesthesia may vary. This study aimed to compare postoperative analgesic efficacy and patient satisfaction in patients who underwent surgery under general anesthesia or sedation-assisted battery replacement under regional anesthesia. Both anesthesia methods are routinely used in Parkinson's disease patients undergoing battery replacement.

Effect of Mediterranean Diet on Nutrition in Parkinson's Disease Patients With Bilateral Subthalamic Deep Brain Stimulation

The goal of this clinical trial is to evaluate whether Mediterranean diet can help manage body weight and improve body composition in adult Parkinson's disease patients who have undergone bilateral subthalamic nucleus deep brain stimulation (STN DBS). The main questions it aims to answer are: Does adherence to the Mediterranean diet for three months post-surgery help control body weight gain in STN DBS patients? Does the Mediterranean diet positively affect body composition and other clinical parameters such as nutritional status, appetite, quality of life, and physical activity? Researchers will compare an intervention group following the Mediterranean diet with a control group continuing their usual diet to see if dietary guidance leads to improvements in weight management, body composition, and other nutritional status parameters. Participants will: Be randomized into intervention and control groups. Receive Mediterranean dietary recommendations (intervention group) or continue usual diet (control group). Undergo evaluations at baseline (pre-operative), and at the 1st, 2nd, and 3rd months post-operatively using the following tools: Visual Appetite Scale Hoehn and Yahr Questionnaire Parkinson's Disease Quality of Life Questionnaire-8 Movement Disorder Society-Unified Parkinson's Disease Rating Scale - Part 2 Mediterranean Diet Adherence Scale Food Consumption Record Have their anthropometric measurements and body composition (e.g., weight, waist and neck circumference, upper arm circumference, handgrip strength) assessed.

Optimization of Deep Brain Stimulation Parameters in Patients With Medically Refractory Epilepsy

Deep brain stimulation (DBS) is used to treat epilepsy in cases where patients are medically refractory and are not candidates for surgical resection. This therapy has been shown to be effective in seizure reduction, yet very few patients achieve the ultimate goal of seizure freedom. Implantable neural stimulators (INSs) have many parameters that may be adjusted, and could be tuned to achieve very patient specific therapies. This study will develop a platform for stimulation setting optimization based on power spectral density (PSD) measures.

Cognitive Decline Following Deep Brain Stimulation: A DBS-fMRI Study

The objective of this research study is to understand how Deep Brain Stimulation (DBS) targeting the subthalamic nucleus (STN) affects cognitive networks in the brain, potentially leading to cognitive decline in patients with Parkinson's Disease (PD). A total of 55 participants with PD who have undergone DBS surgery will be recruited from MUSC's Clinical DBS Program. Participants will attend two post-DBS visits: a 3-hour visit for consent, demographic, and cognitive assessments, and a 3-hour DBS-MRI visit to evaluate brain network connectivity with stimulation ON and OFF. These findings will help improve patient selection for surgery and optimize the selection of stimulation targets that minimize undesirable cognitive side effects.

Consensus Statements on Deep Brain Stimulation in Patients With Parkinson's Disease

Deep brain stimulation (DBS) has become a cornerstone therapy for advanced Parkinson's disease (PD), showing superior outcomes over best medical treatment in randomized clinical trials. By delivering adjustable electrical stimulation to key basal ganglia targets, DBS improves tremor, rigidity, bradykinesia, and motor fluctuations, while also reducing dopaminergic medication requirements. Its success, however, depends not only on precise surgical targeting but also on careful patient selection, multidisciplinary planning, and structured long-term follow-up. In Italy, PD affects nearly 176,000 individuals, of whom an estimated 2-4.5% are potential candidates for DBS. A national survey conducted by the Italian Neurosurgery Society (SINch) revealed marked heterogeneity in surgical approaches, target selection, and team composition across DBS centers-reflecting similar international variability. Yet, clear national indications and guidelines have not been established. To address this gap, we conducted an expert consensus using the Delphi methodology.

EEG Measurements to Capture DBS-induced Electric Potentials

To measure the electric fields induced by DBS (deep brain stimulation) on the scalp and to improve electric field simulations, the investigators will measure EEG (electroencephalography) measurements with high sampling rates (\>100 kHz). The investigators hypothesize that we can improve electric field simulations of DBS by validating and calibrating the simulations based on EEG measurements at high sampling rates (\>100 kHz).

Imaging Biomarkers of FOG Response to DBS

For this study, the investigators are recruiting 54 individuals with Parkinson's Disease and Freezing of Gait (FOG) who are planning to undergo Deep Brain Stimulation (DBS). The objective of this study is to better understand the FOG response to DBS. Prior to DBS, participants will undergo an MRI scan, behavioral assessment related to walking, a cognitive evaluation, and assessment of other Parkinson's disease symptoms. Following DBS, participants will repeat these assessments at multiple timepoints over the period of one year. Overall, participants will complete a total of 7 visits over a period of approximately 1 year.

Deep Brain Stimulation Recovery in Treatment-Resistant Schizophrenia

The purpose of this project is to improve the clinical response and personal recovery of patients with treatment-resistant schizophrenia (TRS).

The STEREO-DBS Study: 7-Tesla MRI Brain Network Analysis for Deep Brain Stimulation

Rationale: Deep brain stimulation (DBS) of the nucleus subthalamicus (STN) is an effective surgical treatment for the patients with advanced Parkinson's disease, despite optimal pharmacological treatment. However, individual improvement after DBS remains variable and 50% of patients show insufficient benefit. To date, DBS-electrode placement and settings in the highly connected STN are based on 1,5-Tesla or 3-Tesla MR-images. These low resolution and solely structural modalities are unable to visualize the multiple brain networks to this small nucleus and prevent electrode activation directed at its cortical projections. By using structural 7-Tesla MRI (7T MRI) connectivity to visualize (malfunctioning) brain networks, DBS-electrode placement and activation can be individualized. Objective: Primary objective of the study is to determine whether visualisation of cortical projections originating in the STN and the position of the DBS electrode relative to these projections using 7T MRI improves motor symptoms as measured by the disease-specific Unified Parkinson's Disease Rating Scale (UPDRS-III). Secondary outcomes are: disease related daily functioning, adverse effects, operation time, quality of life, patient satisfaction with treatment outcome and patient evaluation of treatment burden. Study design: The study will be a single center prospective observational study. Study population: Enrollment will be ongoing from April 2022. Intervention (if applicable): No intervention will be applied. Application of 7T MRI for DBS is standard care and outcome scores used will be readily accessible from the already existing advanced electronic DBS database. Main study parameters/endpoints: The primary outcome measure is the change in motor symptoms as measured by the disease-specific Unified Parkinson's Disease Rating Scale (UPDRS-III). This is measured after 6 months of DBS as part of standard care. The secondary outcome measures are the Amsterdam Linear Disability Score for functional health status, Parkinson's Disease Questionnaire 39, Starkstein apathy scale, patient satisfaction with the treatment, patient evaluation of treatment burden, operating time, hospitalization time, change of tremor medication, side effects and complications. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The proposed observational research project involves treatment options that are standard care in daily practice. The therapies will not be combined with other research products. Participation in this study constitutes negligible risk according to NFU criteria for human research.