Brain Stimulation for Parkinson's Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Alabama at Birmingham
Must be taking: Dopaminergic medications
Must not be taking: Anticoagulants
Disqualifiers: Uncontrolled hypertension, Heart disease, Dementia, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?Our goal is to better understand how DBS modifies local neuronal activity and to pioneer device technologies that can record local DBS-evoked potentials (DLEPs) to guide therapy. Our vision is for a patient's unique electrophysiology to guide both electrode targeting during surgery and programming in clinic, eventually as an integrated component of the implanted pulse generator. Our results will inform directional DBS for PD and serve as a model for translation to other diseases where knowledge on DBS circuit interactions is at an even earlier stage.
Will I have to stop taking my current medications?
The trial requires that participants have stable doses of Parkinson's disease medications for at least 28 days before starting the study. This means you should not change your current medications leading up to the trial.
What data supports the effectiveness of the treatment Neuromodulation eXperiment Testbed system (NEXT) stimulation, Deep Brain Stimulation, DBS for Parkinson's Disease?
Research shows that adaptive deep brain stimulation (aDBS), a form of DBS, can improve treatment for Parkinson's disease by adjusting stimulation in real-time, leading to better clinical scores and reduced power consumption compared to traditional DBS. DBS has been effective for various movement disorders and is FDA-approved for Parkinson's disease, indicating its potential effectiveness.
12345Is deep brain stimulation safe for humans?
Deep brain stimulation (DBS) is generally considered safe, but it can have complications. Common issues include infections, device malfunctions, and lead migrations (movement of the wires). Serious complications like brain bleeds or permanent neurological problems occur in a small percentage of cases.
678910How is the NEXT stimulation treatment different from other treatments for Parkinson's disease?
The NEXT stimulation treatment is unique because it is a fully implantable, wireless, and battery-free system that allows for real-time control of stimulation parameters, unlike traditional deep brain stimulation (DBS) systems that require frequent handling or tethering. This novel approach enables more flexible and long-term management of Parkinson's disease symptoms without the need for external power sources.
24111213Eligibility Criteria
This trial is for adults over 18 with advanced Parkinson's Disease (PD), showing at least two of three main PD symptoms, and having had the disease for four years or more. Candidates must be planning to undergo awake DBS surgery where either STN or GPi is the target, have a mostly normal brain MRI, can cooperate during surgery/post-op evaluations, and have insurance covering DBS as routine care. They should also have refractory motor symptoms despite treatment.Inclusion Criteria
You need to have a brain MRI that shows no major problems, unless it's related to advanced PD.
I am willing and able to cooperate during awake brain surgery and follow-up care.
My movement symptoms are severe and not improving with medication, as confirmed by a medical team.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Surgery and Initial Assessment
Standard of care DBS surgery and initial assessment of brain signals using an external stimulation/recording system
1 week
2 visits (in-person)
Treatment Arm 1
Stimulation from either STN alone, GPi alone, or a combination of both STN and GPi
4 months
Treatment Arm 2
Stimulation from either STN alone, GPi alone, or a combination of both STN and GPi, whichever was not used in Arm 1
4 months
Treatment Arm 3
Stimulation from either STN alone, GPi alone, or a combination of both STN and GPi, whichever was not used in Arms 1 and 2
4 months
Open-label Extension
Unblinded open-label encounter utilizing optimized stimulation parameters
16 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 months
Participant Groups
The study tests whether new deep brain stimulation (DBS) device technologies can create and record brain rhythms to identify optimal locations for clinical stimulation in treating Parkinson's Disease. It involves using the NEXT system during awake DBS surgeries on patients who've chosen this as part of their standard care.
3Treatment groups
Experimental Treatment
Group I: Arm 3 (8-12 months)Experimental Treatment1 Intervention
In this arm we will stimulate from either STN alone, GPi alone, or a combination of both STN and GPi, whichever was not used in Arms 1 and 2.
Group II: Arm 2 (4-8 months)Experimental Treatment1 Intervention
In this arm we will stimulate from either STN alone, GPi alone, or a combination of both STN and GPi, whichever was not used in Arm 1.
Group III: Arm 1 (0-4 months)Experimental Treatment1 Intervention
In this arm we will stimulate from either STN alone, GPi alone, or a combination of both STN and GPi.
Neuromodulation eXperiment Testbed system (NEXT) stimulation is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Deep Brain Stimulation for:
- Parkinson's disease
- Essential tremor
- Epilepsy
🇪🇺 Approved in European Union as Deep Brain Stimulation for:
- Parkinson's disease
- Essential tremor
- Dystonia
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Alabama at BirminghamBirmingham, AL
Loading ...
Who Is Running the Clinical Trial?
University of Alabama at BirminghamLead Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)Collaborator
References
Controlling Parkinson's disease with adaptive deep brain stimulation. [2022]Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson's disease by optimizing stimulation in real time according to fluctuating disease and medication state. In the present realization of adaptive DBS we record and stimulate from the DBS electrodes implanted in the subthalamic nucleus of patients with Parkinson's disease in the early post-operative period. Local field potentials are analogue filtered between 3 and 47 Hz before being passed to a data acquisition unit where they are digitally filtered again around the patient specific beta peak, rectified and smoothed to give an online reading of the beta amplitude. A threshold for beta amplitude is set heuristically, which, if crossed, passes a trigger signal to the stimulator. The stimulator then ramps up stimulation to a pre-determined clinically effective voltage over 250 msec and continues to stimulate until the beta amplitude again falls down below threshold. Stimulation continues in this manner with brief episodes of ramped DBS during periods of heightened beta power. Clinical efficacy is assessed after a minimum period of stabilization (5 min) through the unblinded and blinded video assessment of motor function using a selection of scores from the Unified Parkinson's Rating Scale (UPDRS). Recent work has demonstrated a reduction in power consumption with aDBS as well as an improvement in clinical scores compared to conventional DBS. Chronic aDBS could now be trialed in Parkinsonism.
History, applications, and mechanisms of deep brain stimulation. [2023]Deep brain stimulation (DBS) is an effective surgical treatment for medication-refractory hypokinetic and hyperkinetic movement disorders, and it is being explored for a variety of other neurological and psychiatric diseases. Deep brain stimulation has been Food and Drug Administration-approved for essential tremor and Parkinson disease and has a humanitarian device exemption for dystonia and obsessive-compulsive disorder. Neurostimulation is the fruit of decades of both technical and scientific advances in the field of basic neuroscience and functional neurosurgery. Despite the clinical success of DBS, the therapeutic mechanism of DBS remains under debate. Our objective is to provide a comprehensive review of DBS focusing on movement disorders, including the historical evolution of the technique, applications and outcomes with an overview of the most pertinent literature, current views on mechanisms of stimulation, and description of hardware and programming techniques. We conclude with a discussion of future developments in neurostimulation.
Deep brain stimulation: technology at the cutting edge. [2021]Deep brain stimulation (DBS) surgery has been performed in over 75,000 people worldwide, and has been shown to be an effective treatment for Parkinson's disease, tremor, dystonia, epilepsy, depression, Tourette's syndrome, and obsessive compulsive disorder. We review current and emerging evidence for the role of DBS in the management of a range of neurological and psychiatric conditions, and discuss the technical and practical aspects of performing DBS surgery. In the future, evolution of DBS technology may depend on several key areas, including better scientific understanding of its underlying mechanism of action, advances in high-spatial resolution imaging and development of novel electrophysiological and neurotransmitter microsensor systems. Such developments could form the basis of an intelligent closed-loop DBS system with feedback-guided neuromodulation to optimize both electrode placement and therapeutic efficacy.
[Deep brain stimulation of subthalamic nucleous in Parkinson's disease]. [2019]We present the preliminary results in patients well selected to be implanted by deep brain stimulation (DBS) for Parkinsons's disease (PD).
Proceedings of the Sixth Deep Brain Stimulation Think Tank Modulation of Brain Networks and Application of Advanced Neuroimaging, Neurophysiology, and Optogenetics. [2020]The annual deep brain stimulation (DBS) Think Tank aims to create an opportunity for a multidisciplinary discussion in the field of neuromodulation to examine developments, opportunities and challenges in the field. The proceedings of the Sixth Annual Think Tank recapitulate progress in applications of neurotechnology, neurophysiology, and emerging techniques for the treatment of a range of psychiatric and neurological conditions including Parkinson's disease, essential tremor, Tourette syndrome, epilepsy, cognitive disorders, and addiction. Each section of this overview provides insight about the understanding of neuromodulation for specific disease and discusses current challenges and future directions. This year's report addresses key issues in implementing advanced neurophysiological techniques, evolving use of novel modulation techniques to deliver DBS, ans improved neuroimaging techniques. The proceedings also offer insights into the new era of brain network neuromodulation and connectomic DBS to define and target dysfunctional brain networks. The proceedings also focused on innovations in applications and understanding of adaptive DBS (closed-loop systems), the use and applications of optogenetics in the field of neurostimulation and the need to develop databases for DBS indications. Finally, updates on neuroethical, legal, social, and policy issues relevant to DBS research are discussed.
Treatment results: Parkinson's disease. [2019]Deep brain stimulation (DBS) is a neurosurgical treatment of Parkinson's disease that is applied to three targets: the ventral intermediate nucleus of the thalamus (Vim), the globus pallidus internas (GPi) and the subthalamic nucleus (STN). Vim DBS mainly improves contralateral tremor and, therefore, is being supplanted by DBS of the two other targets, even in patients with tremor dominant disease. STN and GPi DBS improve off-motor phases and dyskinesias. There is little comparative data between these procedures. The magnitude of the motor improvement seems more constant with STN than GPi DBS. STN DBS allows a decrease in antiparkinsonian drug doses and consumes moderate current. These advantages of STN over GPi DBS are offset by the need for more intensive postoperative management. The DBS procedure has the unique advantage of reversibility and adjustability over time. Patients with young-onset Parkinson's disease suffering from levodopa-induced motor complications but still responding well to levodopa and who exhibit no behavioral, mood, or cognitive impairment benefit the most from STN DBS. Adverse effects more specific of the DBS procedure are infection, cutaneous erosion, and lead breaking or disconnection. Intracranial electrode implantation can induce a hematoma or contusion. Most authors agree that the benefit to risk ratio of DBS is favorable.
Safety considerations for deep brain stimulation: review and analysis. [2007]Deep brain stimulation has emerged rapidly as an effective therapy for movement disorders. Deep brain stimulation includes an implanted brain electrode and a pacemaker-like implanted pulse generator. The clinical application of deep brain stimulation proceeded in the absence of clear understandings of its mechanisms of action or extensive preclinical studies of safety and efficacy. Post mortem studies suggest that there is a loss of neurons in proximity to the active electrode, but the resulting lesions are not sufficient to treat the disorder and efficacy requires continued stimulation. Overall complication rates can exceed 25%, and permanent neurologic sequelae result in 4-6% of cases. As the application of deep brain stimulation expands, it is critical to understand the origin of adverse events and the delivery of nondamaging stimulation.
Characterizing Complications of Deep Brain Stimulation Devices for the Treatment of Parkinsonian Symptoms Without Tremor: A Federal MAUDE Database Analysis. [2023]Introduction Deep brain stimulation (DBS) is a modality of treatment for medication refractory Parkinson's disease (PD) in patients with debilitating motor symptoms. While potentially life-changing for individuals with Parkinson's disease, characterization of adverse events for these DBS devices have not yet been systematically organized. Therefore, the goal of this study was to characterize reported complications of DBS devices reported to the Food & Drug Administration over the last 10 years. Methods The Manufacturer and User Facility Device Experience (MAUDE) database was utilized to retrieve entries reported under "Stimulator, Electrical, Implanted, For Parkinsonian Symptoms" between July 31, 2010 and August 1, 2020. After removing duplicate entries, each unique adverse event reported was sorted into complication categories based on the entries' provided narrative description. A final tabulation of complications was generated. Results The search query revealed 221 unique adverse events. The most common DBS devices were the Vercise Gevia, Vercise Cartesia and Vercise PC produced by Boston Scientific (Brian Walker, Boston Scientific, Marlborough, MA, USA). The most commonly reported complications were infection (16.2%) follow by lead migrations (8.6%). Other common causes of complications were circuit-related impedance (6.5%), cerebral bleeds (6.3%), device failure (6.3%) and device-related trauma (4.5%). Over a third (40%) of all devices reported with adverse events required returning to the operating room for explant or revision. Conclusion The most common complications of DBS systems are infections followed by lead migrations. Further research is needed to minimize infection rates associated with DBS systems and to reduce intrinsic device malfunctions for patients in the future.
Older Candidates for Subthalamic Deep Brain Stimulation in Parkinson's Disease Have a Higher Incidence of Psychiatric Serious Adverse Events. [2020]To investigate the incidence of serious adverse events (SAE) of subthalamic deep brain stimulation (STN-DBS) in elderly patients with Parkinson's disease (PD).
Efficacy and safety of deep brain stimulation as an adjunct to pharmacotherapy for the treatment of Parkinson disease. [2012]To review the literature describing the efficacy and safety of deep brain stimulation (DBS) as an adjunct to pharmacotherapy and to determine the best treatment option for patients with Parkinson disease (PD).
Wireless, battery-free, and fully implantable electrical neurostimulation in freely moving rodents. [2021]Implantable deep brain stimulation (DBS) systems are utilized for clinical treatment of diseases such as Parkinson's disease and chronic pain. However, long-term efficacy of DBS is limited, and chronic neuroplastic changes and associated therapeutic mechanisms are not well understood. Fundamental and mechanistic investigation, typically accomplished in small animal models, is difficult because of the need for chronic stimulators that currently require either frequent handling of test subjects to charge battery-powered systems or specialized setups to manage tethers that restrict experimental paradigms and compromise insight. To overcome these challenges, we demonstrate a fully implantable, wireless, battery-free platform that allows for chronic DBS in rodents with the capability to control stimulation parameters digitally in real time. The devices are able to provide stimulation over a wide range of frequencies with biphasic pulses and constant voltage control via low-impedance, surface-engineered platinum electrodes. The devices utilize off-the-shelf components and feature the ability to customize electrodes to enable broad utility and rapid dissemination. Efficacy of the system is demonstrated with a readout of stimulation-evoked neural activity in vivo and chronic stimulation of the medial forebrain bundle in freely moving rats to evoke characteristic head motion for over 36 days.
Deep brain stimulation devices: a brief technical history and review. [2009]Deep brain stimulation (DBS)--a broadly accepted therapeutic modality with tens of thousands of patients currently implanted--is the application of implantable electrical stimulation devices to treat neurological disorders. Approved indications include involuntary movement disorders; investigational applications include epilepsy, selected psychiatric disorders, and other conditions. DBS differs fundamentally from functional electrical stimulation and sensory prosthetics in that DBS therapies do not substitute for or replace injured tissues, organs, or body functions. DBS--targeted to particular brain nuclei or pathways that are specific for the disorder under treatment--influences brain function and behavioral output in ways that can relieve symptoms and improve the overall functioning of the patient. We will briefly review the history and present status of DBS from a technical and device-oriented perspective, with an eye toward future advances.
Neuromodulation: advances in the next five years. [2018]Neuromodulation (deep brain stimulation; DBS) has become an established treatment for movement disorders (e.g., Parkinson's disease), and is in trials for refractory epilepsy, headache, and certain mood disorders. Two main themes will advance DBS significantly in the next five years: closed-loop DBS, that is, feedback from brain electrical activity to direct the stimulation; and computational analysis (CA)--electrophysiological modeling to enhance DBS. Closed-loop DBS is currently in clinical trials for refractory epilepsy. New imaging techniques offer preoperative modeling for DBS surgery, including nerve fiber tracts (diffusion tensor imaging), and imaging of volume of tissue activated by a specific electrode. CA techniques for DBS include mathematical models of the abnormally synchronized electrical activity which underlies epilepsy, movement disorders, and likely many mood disorders as well. By incorporating feedback loops and multiple recording and/or stimulating sites, the abnormally synchronized brain electrical activity can be desynchronized, then "unlearned" ("unkindling" in epilepsy). Characteristics of DBS utilizing CA include low frequency rather than high frequency stimulation; multiple stimulation and/or recording sites; likely 10-fold or more reduction in electrical current needs (much smaller "pulse generators"); more focused and less disruptive stimulation--fewer unwanted side effects; and potential to "cure" certain disorders by resetting abnormal firing patterns back to normal. These advantages of more sophisticated DBS techniques bring the following challenges, which may require a decade of research before reaching clinical practice because many brain disorders involve neurotransmitter abnormalities (e.g., dopamine in Parkinson's disease and certain mood disorders). Namely, how do we monitor and modulate neurotransmitters in addition to electrical activity? How do we get multiple microelectrodes into the brain in a minimally invasive manner? In the accompanying article, I address these two issues and offer some potential solutions.