Personalized Real-Time Deep 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: Phase 4
Recruiting
Sponsor: David Escobar
Must be taking: Levodopa
Disqualifiers: Secondary Parkinsonism, Stroke, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
A prospective cohort of patients scheduled to undergo deep brain stimulation (DBS) implantation surgery for the treatment of Parkinson's disease as per standard of care will be invited to participate in this study. This mechanistic study is aimed at better understanding the role of basal ganglia beta band (11-35 Hz) oscillations and resonance in the manifestation of Parkinson's disease (PD) motor signs using closed-loop electrical neurostimulation, levodopa medication, and computational modeling. The ultimate goal of this study is to inform the development of closed-loop neuromodulation technology that can be programmed and adjusted in real time based on patient-specific neural activity.
Do I need to stop my current medications for this trial?
The trial does not specify if you need to stop your current medications, but it mentions that participants must be able to tolerate delays in taking their daily Parkinson's disease medications.
What data supports the effectiveness of the treatment Personalized Real-Time Deep Brain Stimulation for Parkinson's Disease?
Deep brain stimulation (DBS) has been shown to significantly reduce symptoms like off time and dyskinesia (involuntary movements) in Parkinson's disease patients who do not respond well to medication. It is a well-established treatment that influences brain function to relieve symptoms and improve overall functioning.12345
Is personalized real-time deep brain stimulation for Parkinson's disease generally safe in humans?
Research on electrical stimulation techniques, like peripheral nerve stimulation and spinal cord stimulation, suggests they are generally safe for humans. Long-term studies show only minor tissue reactions, such as fibrous encapsulation, indicating histological safety. Peripheral nerve stimulation has been used safely for decades in various applications.678910
How is the treatment Personalized Real-Time Deep Brain Stimulation for Parkinson's Disease different from other treatments?
Eligibility Criteria
This trial is for people with Parkinson's Disease who are candidates for deep brain stimulation (DBS) surgery. Participants must be able to consent, tolerate delays in their regular medication, and not have conditions like secondary Parkinsonism or stroke.Inclusion Criteria
I am a candidate for a specific brain surgery to help with my condition.
I have been diagnosed with Parkinson's disease without a known cause.
I can manage if there's a delay in my Parkinson's medication.
See 1 more
Exclusion Criteria
I do not have Parkinson's but have other brain conditions like stroke.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
DBS Surgery and Initial Assessment
Participants undergo DBS implantation surgery and initial assessments are conducted
1 week
In-person visits for surgery and initial assessments
Treatment and Assessment
Participants receive closed-loop DBS and levodopa medication, with assessments conducted multiple times
9 days
Multiple in-person visits for assessments
Follow-up
Participants are monitored for changes in motor function and neural oscillations
3-12 months
1 visit (in-person) for follow-up assessments
Treatment Details
Interventions
- Carbidopa/Levodopa (Drug)
- Neurostimulation (Procedure)
Trial OverviewThe study tests how well a personalized real-time DBS system works alongside standard medications like Carbidopa/Levodopa. It aims to understand the role of certain brain oscillations in Parkinson's and develop technology that adjusts treatment based on individual neural activity.
Participant Groups
4Treatment groups
Experimental Treatment
Active Control
Group I: eiDBS suppressionExperimental Treatment1 Intervention
Closed-loop evoked interference DBS that suppresses beta oscillations.
Group II: eiDBS amplificationExperimental Treatment1 Intervention
Closed-loop evoked interference DBS that amplifies beta oscillations.
Group III: Levodopa medicationExperimental Treatment1 Intervention
On-medication, off-stimulation
Group IV: Off DBSActive Control1 Intervention
Off-stimulation and off-medication
Neurostimulation is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Neurostimulation for:
- Respiratory dysfunction in spinal cord injury patients
🇪🇺 Approved in European Union as Neurostimulation for:
- Respiratory failure in spinal cord injury patients
- Neuropathic pain relief
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cleveland ClinicCleveland, OH
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Who Is Running the Clinical Trial?
David EscobarLead Sponsor
The Cleveland ClinicCollaborator
References
Surgical treatment of Parkinson disease: past, present, and future. [2021]Advances in functional neurosurgery have expanded the treatment of Parkinson disease (PD) to targeted electrical stimulation of specific nodes in the basal ganglia circuitry. Deep brain stimulation (DBS), applied to selected patients and difficult-to-manage motor fluctuations, yields substantial reductions in off time and dyskinesia. Emerging concepts in DBS include examination of new targets, such as the potential efficacy of pedunculopontine nucleus stimulation for treatment of freezing and falls, the use of pathologic oscillations in the beta band to construct an adaptive "closed-loop" DBS, and new technologies, including segmented electrodes to steer current toward specific neural populations.
Deep brain stimulation: foundations and future trends. [2022]Deep brain stimulation (DBS) has emerged as a revolutionary treatment option for essential tremor (ET), Parkinson's disease (PD), idiopathic dystonia, and severe obsessive-compulsive disorder (OCD). This article reviews the historical foundations of DBS including basal ganglia pathophysiological models, classic principles of electrical stimulation, technical components of the DBS system, treatment risks, and future directions for DBS. Chronic high frequency stimulation induces a number of functional changes from fast physiological to slower metabolic effects and ultimately leads to structural reorganization of the brain, so-called neuroplasticity. Examples of each of these fast, slow, and long-term changes are given in the context of Parkinson's disease where these mechanisms have perhaps been the most intensely investigated. In particular, details of striatal dopamine release, expression of trophic factors, and a possible neuroprotective mechanism of DBS are highlighted. We close with a brief discussion of technical and clinical considerations for improvement. Deep brain stimulation will continue to offer a reversible and safe therapeutic option for a host of neurological conditions and remains one of the best windows into human brain physiology.
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.
An introduction to operative neuromodulation and functional neuroprosthetics, the new frontiers of clinical neuroscience and biotechnology. [2019]Operative neuromodulation is the field of altering electrically or chemically the signal transmission in the nervous system by implanted devices in order to excite, inhibit or tune the activities of neurons or neural networks and produce therapeutic effects. It is a rapidly evolving biomedical and high-technology field on the cutting-edge of developments across a wide range of scientific disciplines. The authors review relevant literature on the neuromodulation procedures that are performed in the spinal cord or peripheral nerves in order to treat a considerable number of conditions such as (a) chronic pain (craniofacial, somatic, pelvic, limb, or due to failed back surgery), (b) spasticity (due to spinal trauma, multiple sclerosis, upper motor neuron disease, dystonia, cerebral palsy, cerebrovascular disease or head trauma), (c) respiratory disorders, (d) cardiovascular ischemia, (e) neuropathic bladder, and (f) bowel dysfunction of neural cause. Functional neuroprosthetics, a field of operative neuromodulation, encompasses the design, construction and implantation of artificial devices capable of generating electrical stimuli, thereby, replacing the function of damaged parts of the nervous system. The present article also reviews important literature on functional neuroprostheses, functional electrical stimulation (FES), and various emerging applications based on microsystems devices, neural engineering, neuroaugmentation, neurostimulation, and assistive technologies. The authors highlight promising lines of research such as endoneural prostheses for peripheral nerve stimulation, closed-loop systems for responsive neurostimulation or implanted microwires for microstimulation of the spinal cord to enable movements of paralyzed limbs. The above growing scientific fields, in combination with biological regenerative methods, are certainly going to enhance the practice of neuromodulation. The range of neuromodulatory procedures in the spine and peripheral nerves and the dynamics of the biomedical and technological domains which are reviewed in this article indicate that new breakthroughs are likely to improve substantially the quality of life of patients who are severely disabled by neurological disorders.
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.
Refractory neuropathic pain from a median nerve injury: spinal cord or peripheral nerve stimulation? A case report. [2022]Spinal cord stimulation (SCS) is the most frequently used neuromodulation technique even for neurogenic pain from a peripheral nerve injury although peripheral nerve stimulation (PNS) has been designed for this purpose. PNS appears less invasive than SCS or deep brain stimulation. It provides greater and specific target coverage and it could be more cost-effective than SCS because low electrical stimulation is exclusively delivered to the precise painful territory. We report a case of excellent result following median nerve stimulation at arm level after SCS failure and a 10-year history of intense pain. PNS would certainly have been considered much earlier if it was accepted and reimbursed by the Belgium National Insurance. PNS is a safe, simple, and efficient technique available for decades but it is still considered as experimental and underemployed. Belgian National Insurance fears an explosion of indications on neuromodulation if PNS was reimbursed. We consider that PNS aside SCS and other neuromodulation techniques should be made available in Belgium in case of peripheral chronic neuropathic pain.
Some Non-FDA Approved Uses for Neuromodulation: A Review of the Evidence. [2018]Neuromodulation, including spinal cord stimulation and peripheral nerve field stimulation, has been used with success in treating several painful conditions. The FDA approved the use of neuromodulation for a few indications. We review evidence for neuromodulation in treating some important painful conditions that are not currently FDA approved.
Histological reaction to percutaneous epidural neurostimulation: initial and long-term results. [2004]Percutaneously inserted spinal epidural neurostimulation has been derived as a simplified safe alternative to surgically implanted, dorsal column stimulation that is used in the effective treatment and control of spasticity and intractable pain. Twenty-seven tissue specimens from fifteen patients having had percutaneous epidural neurostimulation systems implanted were studied with the aid of light microscopy. The biopsies from tissues around the cables, around the receivers, and at the actual site of epidural stimulation (at the metallic contact), were studied at time intervals varying from one week to two years postimplantation. Long-term results, which only show dense fibrous encapsulation of the cables and the receiver, substantiate clinical belief regarding the "histological safety" of this electronic modality.
Safety of long-term electrical peripheral nerve stimulation: review of the state of the art. [2021]Electrical stimulation of peripheral nerves is used in a variety of applications such as restoring motor function in paralyzed limbs, and more recently, as means to provide intuitive sensory feedback in limb prostheses. However, literature on the safety requirements for stimulation is scarce, particularly for chronic applications. Some aspects of nerve interfacing such as the effect of stimulation parameters on electrochemical processes and charge limitations have been reviewed, but often only for applications in the central nervous system. This review focuses on the safety of electrical stimulation of peripheral nerve in humans.
Implantable neurotechnologies: electrical stimulation and applications. [2018]Neural stimulation using injected electrical charge is widely used both in functional therapies and as an experimental tool for neuroscience applications. Electrical pulses can induce excitation of targeted neural pathways that aid in the treatment of neural disorders or dysfunction of the central and peripheral nervous system. In this review, we summarize the recent trends in the field of electrical stimulation for therapeutic interventions of nervous system disorders, such as for the restoration of brain, eye, ear, spinal cord, nerve and muscle function. Neural prosthetic applications are discussed, and functional electrical stimulation parameters for treating such disorders are reviewed. Important considerations for implantable packaging and enhancing device reliability are also discussed. Neural stimulators are expected to play a profound role in implantable neural devices that treat disorders and help restore functions in injured or disabled nervous system.
Configuration of electrical spinal cord stimulation through real-time processing of gait kinematics. [2021]Epidural electrical stimulation (EES) of the spinal cord and real-time processing of gait kinematics are powerful methods for the study of locomotion and the improvement of motor control after injury or in neurological disorders. Here, we describe equipment and surgical procedures that can be used to acquire chronic electromyographic (EMG) recordings from leg muscles and to implant targeted spinal cord stimulation systems that remain stable up to several months after implantation in rats and nonhuman primates. We also detail how to exploit these implants to configure electrical spinal cord stimulation policies that allow control over the degree of extension and flexion of each leg during locomotion. This protocol uses real-time processing of gait kinematics and locomotor performance, and can be configured within a few days. Once configured, stimulation bursts are delivered over specific spinal cord locations with precise timing that reproduces the natural spatiotemporal activation of motoneurons during locomotion. These protocols can also be easily adapted for the safe implantation of systems in the vicinity of the spinal cord and to conduct experiments involving real-time movement feedback and closed-loop controllers.
Functional neurosurgery for movement disorders: a historical perspective. [2009]Since the 1960s, deep brain stimulation and spinal cord stimulation at low frequency (30 Hz) have been used to treat intractable pain of various origins. For this purpose, specific hardware have been designed, including deep brain electrodes, extensions, and implantable programmable generators (IPGs). In the meantime, movement disorders, and particularly parkinsonian and essential tremors, were treated by electrolytic or mechanic lesions in various targets of the basal ganglia, particularly in the thalamus and in the internal pallidum. The advent in the 1960s of levodopa, as well as the side effects and complications of ablative surgery (e.g., thalamotomy and pallidotomy), has sent functional neurosurgery of movement disorders to oblivion. In 1987, the serendipitous discovery of the effect of high-frequency stimulation (HFS), mimicking lesions, allowed the revival of the surgery of movement disorders by stimulation of the thalamus, which treated tremors with limited morbidity, and adaptable and reversible results. The stability along time of these effects allowed extending it to new targets suggested by basic research in monkeys. The HFS of the subthalamic nucleus (STN) has profoundly challenged the practice of functional surgery as the effect on the triad of dopaminergic symptoms was very significant, allowing to decrease the drug dosage and therefore a decrease of their complications, the levodopa-induced dyskinesias. In the meantime, based on the results of previous basic research in various fields, HFS has been progressively extended to potentially treat epilepsy and, more recently, psychiatric disorders, such as obsessive-compulsive disorders, Gilles de la Tourette tics, and severe depression. Similarly, suggested by the observation of changes in PET scan, applications have been extended to cluster headaches by stimulation of the posterior hypothalamus and even more recently, to obesity and drug addiction. In the field of movement disorders, it has become clear that STN stimulation is not efficient on the nondopaminergic symptoms such as freezing of gait. Based on experimental data obtained in MPTP-treated parkinsonian monkeys, the pedunculopontine nucleus has been used as a new target, and as suggested by the animal research results, its use indeed improves walking and stability when stimulation is performed at low frequency (25 Hz). The concept of simultaneous stimulation of multiple targets eventually at low or high frequency, and that of several electrodes in one target, is being accepted to increase the efficiency. This leads to and is being facilitated by the development of new hardware (multiple-channel IPGs, specific electrodes, rechargeable batteries). Still additional efforts are needed at the level of the stimulation paradigm and in the waveform. The recent development of nanotechnologies allows the design of totally new systems expanding the field of deep brain stimulation. These new techniques will make it possible to not only inhibit or excite deep brain structures to alleviate abnormal symptoms but also open the field for the use of recording cortical activities to drive neuroprostheses through brain-computer interfaces. The new field of compensation of deficits will then become part of the field of functional neurosurgery.
DBS and electrical neuro-network modulation to treat neurological disorders. [2012]The use of neuromodulatory techniques in the treatment of neurological disorders is expanding and now includes devices targeting the motor cortex, basal ganglia, spinal cord, peripheral nervous system, and autonomic nervous system. In this chapter, we review and discuss the current and past literature as well as review indications for each of these devices in the ongoing management of many common neurological diseases including chronic pain, Parkinson's disease, tremor, dystonia, and epilepsy. We also discuss and update mechanisms of deep brain stimulation and electrical neuro-network modulation.