Closed Loop DBS for Parkinson's Disease

Recruiting in Palo Alto (17 mi)

Overseen by Helen M Bronte-Stewart, MD MSE

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Stanford University

Disqualifiers: Dementia, Untreated psychiatric disease, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Deep Brain Stimulation of the subthalamic nucleus (STN) has become a standard of care, FDA-approved treatment for Parkinson's disease, with stimulation delivered at a constant amplitude and voltage, operating in an open-loop fashion that does not respond to a patient's current state. Although gait deficits and freezing of gait may initially respond to continuous open-loop deep brain stimulation (olDBS) and medication, the symptoms often recur over time. The episodic and predictable nature of FOG makes it well suited for adaptive DBS (aDBS) and a device that overcomes the limitations of traditional high frequency olDBS and is capable of adapting therapy either in the frequency or intensity domain transiently to treat FOG while also treating other PD signs such as tremor and bradykinesia. The purpose of this study is to determine the feasibility of an adaptive DBS system, that responds to patient-specific neural and kinematic variables with customized DBS parameters.

Do I need to stop my current medications for this trial?

The protocol does not specify if you need to stop your current medications. However, the trial is for those with complications from medication, so you might continue taking them.

What data supports the idea that Closed Loop DBS for Parkinson's Disease is an effective treatment?

The available research shows that Closed Loop DBS, also known as Adaptive DBS, is effective in treating Parkinson's Disease by using feedback from brain signals to adjust stimulation. This method can lead to significant improvements in motor symptoms, as seen in trials where it improved motor scores more than conventional DBS. It also reduces side effects and extends battery life by using less continuous stimulation. Studies on animals, like rats, have shown that Closed Loop DBS can be more effective than traditional methods, suggesting its potential benefits for humans. ^{1 2 3 4 5}

What safety data exists for closed-loop DBS in Parkinson's Disease?

Closed-loop adaptive deep brain stimulation (aDBS) has been shown to reduce stimulation time and side effects compared to conventional DBS (cDBS). Studies indicate that aDBS is at least as effective as cDBS, with reduced side effects and energy consumption. Common complications of DBS devices include infections, lead migrations, and device malfunctions, with a significant portion requiring surgical intervention. Further research is needed to address these complications and improve device reliability. ^{5 6 7 8 9}

Is Bilateral Closed Loop Deep Brain Stimulation a promising treatment for Parkinson's Disease?

Yes, Bilateral Closed Loop Deep Brain Stimulation is a promising treatment for Parkinson's Disease. It can improve motor symptoms by adjusting the stimulation based on the patient's condition, leading to better control of symptoms and fewer side effects compared to traditional methods. It also uses less energy, which can extend the life of the device used in the treatment. ^{1 4 5 6 10}

Eligibility Criteria

This trial is for adults over 18 with Parkinson's Disease who experience gait issues despite medication. They must be eligible for or already have a specific deep brain stimulation device implanted and can attend follow-up visits. Exclusions include dementia, certain medical devices like pacemakers, severe health conditions, pregnancy, metal implants in the skull, seizures, and advanced-stage Parkinson's.

Inclusion Criteria

I am older than 18 years.

I experience freezing when I walk.

Your nerve response is above a certain level in a specific test.

Exclusion Criteria

You have a heart device called a pacemaker or defibrillator.

I don't have severe high blood pressure, bleeding disorders, or metabolic conditions that could complicate surgery.

I have a history of seizures or epilepsy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adaptive DBS therapy, which responds to neural and kinematic features of the patient's current state, and intermittent open-loop DBS as a control

3 months

Regular visits every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of gait parameters and adverse events

6 months

Collected up to 10 days every 3 months

Treatment Details

Interventions

• Bilateral Closed Loop Deep Brain Stimulation (Procedure)

Trial Overview The study tests an adaptive Deep Brain Stimulation (DBS) system that adjusts its settings based on real-time feedback from the patient's neural activity and movement patterns. It aims to improve walking difficulties in Parkinson’s patients by customizing treatment to their immediate needs.

Participant Groups

Group I: Device: Summit RC+S Experimental Treatment 3 Interventions

1. Open Loop DBS: Standard DBS therapy at a constant frequency and voltage 2. Adaptive (Closed Loop) DBS: DBS that responds to neural or kinematic features of patient's current state 3. Intermittent Open Loop DBS: Control for aDBS - DBS intensity or frequency changes in a manner that mimics aDBS but is pre-determined and open loop rather than being responsive to neural or kinematic signals.

Group II: Device: Percept PC Experimental Treatment 2 Interventions

1. Open Loop DBS: Standard DBS therapy at a constant frequency and voltage 2. Adaptive (Closed Loop) DBS: DBS that responds to neural features of patient's current state

Bilateral Closed Loop Deep Brain 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
• Moderate to advanced levodopa-responsive Parkinson’s disease

🇪🇺 Approved in European Union as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Dystonia

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Stanford University Stanford, CA

Who Is Running the Clinical Trial?

Stanford University Lead Sponsor

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Efficient suppression of parkinsonian beta oscillations in a closed-loop model of deep brain stimulation with amplitude modulation. [2023] Parkinson's disease (PD) is a movement disorder characterized by the pathological beta band (15-30 Hz) neural oscillations within the basal ganglia (BG). It is shown that the suppression of abnormal beta oscillations is correlated with the improvement of PD motor symptoms, which is a goal of standard therapies including deep brain stimulation (DBS). To overcome the stimulation-induced side effects and inefficiencies of conventional DBS (cDBS) and to reduce the administered stimulation current, closed-loop adaptive DBS (aDBS) techniques were developed. In this method, the frequency and/or amplitude of stimulation are modulated based on various disease biomarkers.

2. England pubmed.ncbi.nlm.nih.gov

Bilateral adaptive deep brain stimulation is effective in Parkinson's disease. [2022] Adaptive deep brain stimulation (aDBS) uses feedback from brain signals to guide stimulation. A recent acute trial of unilateral aDBS showed that aDBS can lead to substantial improvements in contralateral hemibody Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and may be superior to conventional continuous DBS in Parkinson's disease (PD). We test whether potential benefits are retained with bilateral aDBS and in the face of concurrent medication.

3. United States pubmed.ncbi.nlm.nih.gov

On-Off and Proportional Closed-Loop Adaptive Deep Brain Stimulation Reduces Motor Symptoms in Freely Moving Hemiparkinsonian Rats. [2023] Closed-loop adaptive deep brain stimulation (aDBS) continuously adjusts stimulation parameters, with the potential to improve efficacy and reduce side effects of deep brain stimulation (DBS) for Parkinson's disease (PD). Rodent models can provide an effective platform for testing aDBS algorithms and establishing efficacy before clinical investigation. In this study, we compare two aDBS algorithms, on-off and proportional modulation of DBS amplitude, with conventional DBS in hemiparkinsonian rats.

4. United States pubmed.ncbi.nlm.nih.gov

Adaptive deep brain stimulation (aDBS) controlled by local field potential oscillations. [2013] Despite their proven efficacy in treating neurological disorders, especially Parkinson's disease, deep brain stimulation (DBS) systems could be further optimized to maximize treatment benefits. In particular, because current open-loop DBS strategies based on fixed stimulation settings leave the typical parkinsonian motor fluctuations and rapid symptom variations partly uncontrolled, research has for several years focused on developing novel "closed-loop" or "adaptive" DBS (aDBS) systems. aDBS consists of a simple closed-loop model designed to measure and analyze a control variable reflecting the patient's clinical condition to elaborate new stimulation settings and send them to an "intelligent" implanted stimulator. The major problem in developing an aDBS system is choosing the ideal control variable for feedback. Here we review current evidence on the advantages of neurosignal-controlled aDBS that uses local field potentials (LFPs) as a control variable, and describe the technology already available to create new aDBS systems, and the potential benefits of aDBS for patients with Parkinson's disease.

5. England pubmed.ncbi.nlm.nih.gov

Toward adaptive deep brain stimulation in Parkinson's disease: a review. [2019] Clinical deep brain stimulation (DBS) is now regarded as the therapeutic intervention of choice at the advanced stages of Parkinson's disease. However, some major challenges of DBS are stimulation induced side effects and limited pacemaker battery life. Side effects and shortening of pacemaker battery life are mainly as a result of continuous stimulation and poor stimulation focus. These drawbacks can be mitigated using adaptive DBS (aDBS) schemes. Side effects resulting from continuous stimulation can be reduced through adaptive control using closed-loop feedback, while those due to poor stimulation focus can be mitigated through spatial adaptation. Other advantages of aDBS include automatic, rather than manual, initial adjustment and programming, and long-term adjustments to maintain stimulation parameters with changes in patient's condition. Both result in improved efficacy. This review focuses on the major areas that are essential in driving technological advances for the various aDBS schemes. Their challenges, prospects and progress so far are analyzed. In addition, important advances and milestones in state-of-the-art aDBS schemes are highlighted - both for closed-loop adaption and spatial adaption. With perspectives and future potentials of DBS provided at the end.

6. United States pubmed.ncbi.nlm.nih.gov

Eight-hours conventional versus adaptive deep brain stimulation of the subthalamic nucleus in Parkinson's disease. [2022] This study compares the effects on motor symptoms between conventional deep brain stimulation (cDBS) and closed-loop adaptive deep brain stimulation (aDBS) in patients with Parkinson's Disease. The aDBS stimulation is controlled by the power in the beta band (12-35 Hz) of local field potentials recorded directly by subthalamic nucleus electrodes. Eight subjects were assessed in two 8-h stimulation sessions (first day, cDBS; second day, aDBS) with regular levodopa intake and during normal daily activities. The Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, the Rush scale for dyskinesias, and the total electrical energy delivered to the tissues per second (TEEDs) were significantly lower in the aDBS session (relative UPDRS mean, cDBS: 0.46 ± 0.05, aDBS: 0.33 ± 0.04, p = 0.015; UPDRS part III rigidity subset mean, cDBS: 2.9143 ± 0.6551 and aDBS: 2.1429 ± 0.5010, p = 0.034; UPDRS part III standard deviation cDBS: 2.95, aDBS: 2.68; p = 0.047; Rush scale, cDBS 2.79 ± 0.39 versus aDBS 1.57 ± 0.23, p = 0.037; cDBS TEEDs mean: 28.75 ± 3.36 µj s-1, aDBS TEEDs mean: 16.47 ± 3.33, p = 0.032 Wilcoxon's sign rank test). This work further supports the safety and effectiveness of aDBS stimulation compared to cDBS in a daily session, both in terms of motor performance and TEED to the patient.

7. United States pubmed.ncbi.nlm.nih.gov

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.

8. England pubmed.ncbi.nlm.nih.gov

The adaptive deep brain stimulation challenge. [2018] Sub-optimal clinical outcomes of conventional deep brain stimulation (cDBS) in treating Parkinson's Disease (PD) have boosted the development of new solutions to improve DBS therapy. Adaptive DBS (aDBS), consisting of closed-loop, real-time changing of stimulation parameters according to the patient's clinical state, promises to achieve this goal and is attracting increasing interest in overcoming all of the challenges posed by its development and adoption. In the design, implementation, and application of aDBS, the choice of the control variable and of the control algorithm represents the core challenge. The proposed approaches, in fact, differ in the choice of the control variable and control policy, in the system design and its technological limits, in the patient's target symptom, and in the surgical procedure needed. Here, we review the current proposals for aDBS systems, focusing on the choice of the control variable and its advantages and drawbacks, thus providing a general overview of the possible pathways for the clinical translation of aDBS with its benefits, limitations and unsolved issues.

9. England pubmed.ncbi.nlm.nih.gov

Adaptive deep brain stimulation as advanced Parkinson's disease treatment (ADAPT study): protocol for a pseudo-randomised clinical study. [2022] Adaptive deep brain stimulation (aDBS), based on the detection of increased beta oscillations in the subthalamic nucleus (STN), has been assessed in patients with Parkinson's disease (PD) during the immediate postoperative setting. In these studies, aDBS was shown to be at least as effective as conventional DBS (cDBS), while stimulation time and side effects were reduced. However, the effect of aDBS on motor symptoms and stimulation-induced side effects during the chronically implanted phase (after the stun effect of DBS placement has disappeared) has not yet been determined.

10. United States pubmed.ncbi.nlm.nih.gov

Dual threshold neural closed loop deep brain stimulation in Parkinson disease patients. [2019] Closed loop deep brain stimulation (clDBS) in Parkinson's disease (PD) using subthalamic (STN) neural feedback has been shown to be efficacious only in the acute post-operative setting, using externalized leads and stimulators.