Brain Stimulation for Parkinson's Disease

Overseen By Christopher Gonzalez

Age: 18+

Sex: Any

Trial Phase: Academic

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 All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

36 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

Is 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. ^{6 7 8 9 10}

How 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. ^{2 4 11 12 13}

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.

Research Team

Harrison Walker, MD

Principal Investigator

University of Alabama at Birmingham

Eligibility 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.

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

Treatment Details

Interventions

• Neuromodulation eXperiment Testbed system (NEXT) stimulation

Trial Overview 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.

Participant Groups

Group I: Arm 3 (8-12 months) Experimental Treatment 1 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 Treatment 1 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 Treatment 1 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

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

Adaptive deep brain stimulation (aDBS) shows promise in improving Parkinson's disease treatment by adjusting stimulation in real-time based on the patient's brain activity, specifically targeting beta amplitude fluctuations.

In early trials, aDBS demonstrated reduced power consumption and improved motor function scores compared to traditional deep brain stimulation, suggesting it could be a more efficient and effective long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlling Parkinson's disease with adaptive deep brain stimulation. Little, S., Pogosyan, A., Neal, S., et al.[2022]

Deep brain stimulation (DBS) is an FDA-approved treatment for essential tremor and Parkinson's disease, and it shows promise for other conditions like dystonia and obsessive-compulsive disorder, making it a versatile option for patients with movement disorders.

The exact mechanism of how DBS works is still debated, highlighting the need for further research to fully understand its therapeutic effects and improve its applications in various neurological and psychiatric diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

History, applications, and mechanisms of deep brain stimulation. Miocinovic, S., Somayajula, S., Chitnis, S., et al.[2023]

Deep brain stimulation (DBS) has been successfully used in over 75,000 patients worldwide to treat various neurological and psychiatric disorders, demonstrating its efficacy in conditions like Parkinson's disease and depression.

Future advancements in DBS technology may lead to intelligent systems that use feedback to optimize treatment, improving both the placement of electrodes and the overall effectiveness of the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation: technology at the cutting edge. Shah, RS., Chang, SY., Min, HK., et al.[2021]

In a preliminary study of 8 patients with Parkinson's disease who had poor responses to medication, deep brain stimulation (DBS) significantly improved motor performance over 6 months, as measured by various scales.

No complications were reported from the DBS procedures, suggesting that it is a safe intervention for selected patients with severe symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Deep brain stimulation of subthalamic nucleous in Parkinson's disease]. Nasser, JA., Falavigna, A., Alaminos, A., et al.[2019]

The Sixth Annual Deep Brain Stimulation (DBS) Think Tank highlighted advancements in neurotechnology and neurophysiology for treating various neurological and psychiatric conditions, emphasizing the importance of understanding brain networks for effective neuromodulation.

Innovations discussed included adaptive DBS systems, optogenetics, and the need for comprehensive databases to improve DBS applications, alongside addressing ethical and policy considerations in the field.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proceedings of the Sixth Deep Brain Stimulation Think Tank Modulation of Brain Networks and Application of Advanced Neuroimaging, Neurophysiology, and Optogenetics. Ramirez-Zamora, A., Giordano, J., Boyden, ES., et al.[2020]

Deep brain stimulation (DBS) for Parkinson's disease, particularly targeting the subthalamic nucleus (STN), provides significant motor improvement and allows for reduced medication doses, making it a preferred option for younger patients with motor complications.

While STN DBS has advantages like better motor control and lower current consumption, it requires more intensive postoperative management and carries risks such as infection and hematoma, though the overall benefit-to-risk ratio is considered favorable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment results: Parkinson's disease. Pollak, P., Fraix, V., Krack, P., et al.[2019]

Deep brain stimulation is an effective treatment for movement disorders, involving an implanted electrode and pulse generator, but its mechanisms of action are not fully understood and were developed without extensive preclinical safety studies.

Complication rates for deep brain stimulation can exceed 25%, with 4-6% of patients experiencing permanent neurological issues, highlighting the need for better understanding of adverse events and safer stimulation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety considerations for deep brain stimulation: review and analysis. Grill, WM.[2007]

A review of 221 unique adverse events related to deep brain stimulation (DBS) devices for Parkinson's disease revealed that the most common complications were infections (16.2%) and lead migrations (8.6%).

Over 40% of the reported adverse events required patients to return to the operating room for device explantation or revision, highlighting the need for further research to improve the safety and reliability of DBS systems.

NCBI (Pubmed)

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. Bennett, J., MacGuire, J., Novakovic, E., et al.[2023]

In a study of 26 elderly patients with Parkinson's disease undergoing subthalamic deep brain stimulation (STN-DBS), there was a higher incidence of serious adverse events, particularly psychosis and hallucinations, compared to younger patients from the EARLYSTIM study.

Despite these psychiatric complications being transient, the overall benefits of STN-DBS in improving Parkinson's symptoms were found to outweigh the risks, highlighting the importance of thorough psychiatric evaluations before and after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Older Candidates for Subthalamic Deep Brain Stimulation in Parkinson's Disease Have a Higher Incidence of Psychiatric Serious Adverse Events. Cozac, VV., Ehrensperger, MM., Gschwandtner, U., et al.[2020]

Deep brain stimulation (DBS) can improve motor function and quality of life in patients with Parkinson's disease when used alongside traditional medication, particularly for those whose symptoms are not well-controlled by medication alone.

However, while DBS offers significant benefits, it also comes with a higher risk of adverse events compared to pharmacotherapy, highlighting the need to carefully consider the risks and benefits before opting for this surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of deep brain stimulation as an adjunct to pharmacotherapy for the treatment of Parkinson disease. Sharma, A., Szeto, K., Desilets, AR.[2012]

A new fully implantable, wireless, battery-free deep brain stimulation (DBS) system has been developed for chronic use in rodents, allowing for real-time control of stimulation parameters without the limitations of tethered systems.

This innovative DBS platform demonstrated efficacy by successfully stimulating the medial forebrain bundle in freely moving rats for over 36 days, evoking characteristic head motion, which suggests its potential for long-term studies on neuroplastic changes and therapeutic mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wireless, battery-free, and fully implantable electrical neurostimulation in freely moving rodents. Burton, A., Won, SM., Sohrabi, AK., et al.[2021]

Deep brain stimulation (DBS) is an established treatment for neurological disorders, currently used in tens of thousands of patients, and is effective for conditions like involuntary movement disorders, with ongoing research into its use for epilepsy and psychiatric disorders.

DBS works by applying electrical stimulation to specific brain areas, influencing brain function and behavior to alleviate symptoms, rather than replacing damaged tissues or organs, highlighting its unique mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation devices: a brief technical history and review. Coffey, RJ.[2009]

Deep brain stimulation (DBS) is evolving with promising advancements like closed-loop systems that use real-time brain activity feedback, currently being tested for refractory epilepsy, which could enhance treatment efficacy and reduce side effects.

Computational analysis (CA) techniques are being developed to improve DBS by modeling abnormal brain activity, potentially allowing for more precise stimulation, lower energy requirements, and the ability to reset abnormal firing patterns, although challenges remain in addressing neurotransmitter imbalances and minimally invasive electrode placement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation: advances in the next five years. Andrews, RJ.[2018]

References

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

Controlling Parkinson's disease with adaptive deep brain stimulation. [2022]

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

History, applications, and mechanisms of deep brain stimulation. [2023]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Deep brain stimulation: technology at the cutting edge. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

[Deep brain stimulation of subthalamic nucleous in Parkinson's disease]. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Proceedings of the Sixth Deep Brain Stimulation Think Tank Modulation of Brain Networks and Application of Advanced Neuroimaging, Neurophysiology, and Optogenetics. [2020]

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

Treatment results: Parkinson's disease. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Safety considerations for deep brain stimulation: review and analysis. [2007]

8. 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]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Older Candidates for Subthalamic Deep Brain Stimulation in Parkinson's Disease Have a Higher Incidence of Psychiatric Serious Adverse Events. [2020]

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

Efficacy and safety of deep brain stimulation as an adjunct to pharmacotherapy for the treatment of Parkinson disease. [2012]

11. England pubmed.ncbi.nlm.nih.gov

Wireless, battery-free, and fully implantable electrical neurostimulation in freely moving rodents. [2021]

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

Deep brain stimulation devices: a brief technical history and review. [2009]

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

Neuromodulation: advances in the next five years. [2018]