DBS Settings Optimization for Parkinson's Disease

Overseen By Scott Cooper, PhD, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Disqualifiers: Inability to walk, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Deep Brain Stimulation (DBS) for Parkinson's Disease?

Deep Brain Stimulation (DBS) has been shown to be a highly effective treatment for advanced Parkinson's disease, improving symptoms and quality of life. Studies highlight the importance of careful programming and patient selection to achieve the best results, and new techniques like 'Coordinated Reset' DBS are being explored to enhance its benefits. ^{1 2 3 4 5}

Is deep brain stimulation (DBS) generally safe for humans?

Deep brain stimulation (DBS) is generally considered safe, but it can have complications. Common issues include infections, lead migrations (movement of the wires), and device malfunctions, with some cases requiring additional surgery. Serious complications like permanent neurological problems occur in 4-6% of cases. ^{6 7 8 9 10}

How is Deep Brain Stimulation (DBS) different from other treatments for Parkinson's disease?

Deep Brain Stimulation (DBS) is unique because it involves implanting electrodes in the brain to send electrical impulses, which can help manage symptoms of Parkinson's disease by altering brain activity. Unlike medications that are taken orally, DBS is a surgical treatment that offers a reversible and adjustable option, allowing for personalized settings to optimize symptom control. ^{1 11 12 13 14}

What is the purpose of this trial?

In Parkinson's disease (PD) patients undergoing standard-of-care Deep Brain Stimulation (DBS) therapy, to compare the effect on Parkinson's symptoms of two different neurostimulator settings designed to differ from each other as much as possible with respect to how much they activate two different neuroanatomical structures: the axonal pathway from Globus Pallidus (GP) to Pedunculopontine Nucleus (PPN), and the axonal pathway from PPN to GP.

Eligibility Criteria

This trial is for Parkinson's Disease patients aged 18-85 with bilateral DBS implants, a cognitive score of at least 23, and who are at least 3 months post-implant. They must have had specific MRI and CT imaging done. Pregnant or nursing women, those with nearly depleted IPG batteries, inability to walk without stimulation, or gait issues not caused by PD cannot join.

Inclusion Criteria

I have been diagnosed with Parkinson's Disease.

My mental ability to understand and decide on treatment is confirmed by tests.

I have had a 7T MRI and a post-op CT scan as required.

Exclusion Criteria

I am currently pregnant or breastfeeding.

I cannot walk by myself when my medication and devices are off.

Breaks or shorts in active contacts

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo two different neurostimulator settings for two weeks to compare effects on Parkinson's symptoms

2 weeks

Multiple sessions including laboratory testing

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of ADL and QOL scales

2 weeks

Treatment Details

Interventions

• Deep Brain Stimulation (DBS)

Trial Overview The study tests two different DBS settings in Parkinson's patients to see how they affect symptoms. The settings differ in their activation of neural pathways between the Globus Pallidus and Pedunculopontine Nucleus.

Deep Brain Stimulation (DBS) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Deep Brain Stimulation for:

• Advanced Parkinson's disease
• Medically refractory tremor
• Dystonia
• Obsessive-compulsive disorder

Approved in European Union as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Dystonia
• Psychiatric conditions

Approved in Canada as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Dystonia

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

Deep brain stimulation (DBS) is a highly effective treatment for advanced Parkinson's disease, with its success relying on careful patient selection and individualized targeting of stimulation parameters.

Recent advancements in DBS hardware allow for more focused stimulation, which can improve clinical outcomes, but also require healthcare providers to adapt to the increased complexity in programming.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on best practice of deep brain stimulation in Parkinson's disease. Hartmann, CJ., Fliegen, S., Groiss, SJ., et al.[2020]

Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease, but it requires careful adherence to specific guidelines when performing MRI to avoid serious complications.

A case study highlighted a permanent neurological injury caused by improper use of MRI in a patient with a DBS device, emphasizing the critical need for following manufacturer guidelines to ensure patient safety during imaging procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Permanent neurological deficit related to magnetic resonance imaging in a patient with implanted deep brain stimulation electrodes for Parkinson's disease: case report. Henderson, JM., Tkach, J., Phillips, M., et al.[2019]

In a study of 44 patients with advanced Parkinson's disease who had been receiving deep brain stimulation (DBS) for an average of 3.5 years, 54.6% showed significant improvements in their symptoms after a neurologist expert reprogrammed their DBS settings and adjusted their medications.

The reprogramming led to a 15.0% improvement in Unified Parkinson's Disease Rating Scale scores for daily living and a 25.9% improvement in motor function, while also allowing for a 25.9% reduction in antiparkinsonian drug dosages, demonstrating the importance of personalized postoperative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthalamic nucleus stimulation: improvements in outcome with reprogramming. Moro, E., Poon, YY., Lozano, AM., et al.[2006]

Deep Brain Stimulation (DBS) is an established treatment for Parkinson's Disease, and standardized postoperative programming can enhance symptom relief and quality of life for patients.

An expert consensus developed by Chinese specialists aims to standardize DBS programming, which is expected to improve the overall management of patients after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chinese expert consensus on programming deep brain stimulation for patients with Parkinson's disease. Chen, S., Gao, G., Feng, T., et al.[2022]

Low-intensity Coordinated Reset (CR) deep brain stimulation (DBS) showed significant motor improvements in a non-human primate model of Parkinson's disease, with benefits that persisted for up to two weeks after treatment, indicating a potential for long-lasting therapeutic effects.

In contrast to traditional DBS, which had limited carry-over effects, CR DBS demonstrated progressive enhancements in motor function with each treatment session, suggesting it may be a safer and more efficient option for managing Parkinson's symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Coordinated Reset Deep Brain Stimulation of Subthalamic Nucleus Produces Long-Lasting, Dose-Dependent Motor Improvements in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Non-Human Primate Model of Parkinsonism. Wang, J., Nebeck, S., Muralidharan, A., et al.[2023]

Deep brain stimulation (DBS) is a safe and effective surgical treatment for advanced Parkinson's disease, with a low incidence of serious complications, as shown in a study of 130 patients over several years.

In this study, 62% of patients experienced no complications, and the most common issues were minor, such as aborted procedures (5.14%) and seizures (4.7%), indicating that DBS has a favorable safety profile compared to other surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications in subthalamic nucleus stimulation surgery for treatment of Parkinson's disease. Review of 272 procedures. Seijo, FJ., Alvarez-Vega, MA., Gutierrez, JC., et al.[2019]

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]

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]

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) significantly improved motor symptoms in a 44-year-old woman with Parkinson's disease, but also caused uncontrollable laughter, highlighting the potential for neurobehavioral side effects.

The use of directional electrodes allowed for more precise stimulation, which helped to minimize undesirable side effects while optimizing motor improvement, suggesting that careful programming and electrode placement are crucial for effective DBS therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-motor Adverse Effects Avoided by Directional Stimulation in Parkinson's Disease: A Case Report. Alonso-Frech, F., Fernandez-Garcia, C., Gómez-Mayordomo, V., et al.[2022]

Effective management after deep brain stimulation (DBS) surgery for conditions like Parkinson's disease relies heavily on the skills of movement disorder specialists in adjusting stimulation parameters and medications.

The authors propose a standardized algorithm for selecting DBS stimulation parameters, which can simplify the complex settings and improve patient outcomes through better clinical and neurophysiological management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introduction to the programming of deep brain stimulators. Volkmann, J., Herzog, J., Kopper, F., et al.[2023]

A semi-automatic algorithm-guided programming (AgP) approach for Deep Brain Stimulation (DBS) in Parkinson's disease showed significant improvement in motor symptoms compared to no therapy, with a median improvement in Unified Parkinson's Disease Rating Scale III scores.

While both AgP and standard of care (SoC) DBS settings provided similar clinical outcomes, AgP required testing of many more settings (37 on average) to find optimal stimulation, indicating it may offer a more tailored approach to DBS programming.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple input algorithm-guided Deep Brain stimulation-programming for Parkinson's disease patients. Gülke, E., Juárez Paz, L., Scholtes, H., et al.[2022]

A new sweet spot-guided algorithm was developed to suggest optimal stimulation parameters for Deep Brain Stimulation (DBS) in 24 Parkinson's disease patients, aiming to reduce the time and discomfort associated with traditional trial-and-error methods.

The algorithm showed a significant improvement in suggesting the best contact for stimulation compared to reconstruction-guided methods, with an accuracy of 41%, while the accuracy for lead levels was 56%, indicating potential for enhanced patient-specific treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programming of subthalamic nucleus deep brain stimulation for Parkinson's disease with sweet spot-guided parameter suggestions. Nordenström, S., Petermann, K., Debove, I., et al.[2022]

Deep brain stimulation (DBS) is a safe and reversible treatment option for neurological conditions like essential tremor, Parkinson's disease, and severe obsessive-compulsive disorder, showing significant functional and structural changes in the brain.

DBS induces neuroplasticity through various mechanisms, including increased striatal dopamine release and expression of trophic factors, which may provide neuroprotective effects, particularly in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation: foundations and future trends. Aum, DJ., Tierney, TS.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

An update on best practice of deep brain stimulation in Parkinson's disease. [2020]

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

Permanent neurological deficit related to magnetic resonance imaging in a patient with implanted deep brain stimulation electrodes for Parkinson's disease: case report. [2019]

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

Subthalamic nucleus stimulation: improvements in outcome with reprogramming. [2006]

4. England pubmed.ncbi.nlm.nih.gov

Chinese expert consensus on programming deep brain stimulation for patients with Parkinson's disease. [2022]

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

Coordinated Reset Deep Brain Stimulation of Subthalamic Nucleus Produces Long-Lasting, Dose-Dependent Motor Improvements in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Non-Human Primate Model of Parkinsonism. [2023]

6. Austria pubmed.ncbi.nlm.nih.gov

Complications in subthalamic nucleus stimulation surgery for treatment of Parkinson's disease. Review of 272 procedures. [2019]

7. 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]

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

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

9. 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]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Non-motor Adverse Effects Avoided by Directional Stimulation in Parkinson's Disease: A Case Report. [2022]

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

Introduction to the programming of deep brain stimulators. [2023]

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

Multiple input algorithm-guided Deep Brain stimulation-programming for Parkinson's disease patients. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Programming of subthalamic nucleus deep brain stimulation for Parkinson's disease with sweet spot-guided parameter suggestions. [2022]

14. Singapore pubmed.ncbi.nlm.nih.gov

Deep brain stimulation: foundations and future trends. [2022]