Deep Brain Stimulation for Parkinson's Disease

Enrolling by invitation at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Disqualifiers: Inability to execute motor tasks, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different patterns of deep brain stimulation (DBS) affect individuals with Parkinson’s disease, essential tremor, dystonia, or multiple sclerosis. Researchers aim to determine if new stimulation patterns, such as Symptogenic Stimulation Patterns and Therapeutic Stimulation Patterns, can better manage motor symptoms and enhance movement. Participants will join one of two groups: one where stimulation patterns might temporarily worsen symptoms, and another where patterns aim to relieve symptoms. Individuals with one of these conditions who are set to receive a DBS implant or replacement and are neurologically stable might be suitable for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to improved treatments for neurological conditions.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants must be able to tolerate withholding anti-parkinsonian and/or anti-tremor medications. This suggests you might need to pause these medications during the study.

What prior data suggests that these deep brain stimulation patterns are safe for Parkinson's disease?

Research has shown that deep brain stimulation (DBS) is generally safe for people with Parkinson's disease. Studies have found that DBS can improve movement and cause fewer side effects than other treatments. Both types of DBS, Symptogenic and Therapeutic, are usually well-tolerated by most patients.

One study that followed DBS patients for five years found it to be safe and effective for Parkinson's. Participants experienced improvements in symptoms like tremors and stiffness. Another study demonstrated that DBS can enhance daily life and lead to fewer issues compared to not using it.

While DBS is considered safe, some people might still experience side effects. These can include mood changes or speech problems, but they are usually manageable. For those considering joining a trial, these studies suggest that DBS is a safe option for treating Parkinson's symptoms. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for Parkinson's Disease because they explore innovative ways to manage motor symptoms using deep brain stimulation (DBS). Unlike traditional DBS, which provides continuous electrical stimulation, these treatments use specific patterns that either exacerbate or suppress neural activity. The Symptogenic Stimulation Patterns are designed to increase oscillatory neural activity, helping researchers understand how these patterns affect motor symptoms. In contrast, the Therapeutic Stimulation Patterns aim to reduce this activity, potentially improving symptoms more precisely and effectively than existing methods. This approach could lead to personalized DBS strategies, offering new hope for those with Parkinson's.

What evidence suggests that this trial's treatments could be effective for Parkinson's disease?

Research has shown that deep brain stimulation (DBS) can help treat movement disorders like Parkinson's disease. Studies have found that DBS can significantly reduce symptoms such as tremors and stiffness. In this trial, participants will receive different stimulation patterns. The therapeutic stimulation patterns aim to decrease specific brain activities linked to these symptoms, providing relief. Conversely, symptogenic patterns are designed to increase these brain activities and worsen symptoms to better understand how DBS works. Overall, DBS has improved the quality of life for many Parkinson's patients by reducing their need for medications and making movement easier. ^{3 6 7 8 9}

Who Is on the Research Team?

Warren M Grill, PhD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for individuals with Parkinson's Disease, Essential Tremor, or Multiple Sclerosis who are neurologically stable and scheduled for Deep Brain Stimulation surgery. Participants must understand the study and consent form. Those unable to perform motor tasks or tolerate medication withdrawal, or with ineffective DBS are excluded.

Inclusion Criteria

My neurological condition is stable.

I have been diagnosed with Parkinson's, Essential Tremor, or Multiple Sclerosis.

Able to understand the study and consent form

Exclusion Criteria

Deep brain stimulation (DBS) is not working to improve symptoms.

I cannot perform certain physical tasks required in the study.

I cannot stop taking my Parkinson's or tremor medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Surgery and Stimulation

Subjects undergo surgery for DBS electrode implantation or IPG replacement, followed by delivery of non-regular temporal patterns of stimulation to measure effects on neural activity and motor symptoms.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the surgical procedure and stimulation.

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Symptogenic Stimulation Patterns
• Therapeutic Stimulation Patterns

Trial Overview The study measures how non-regular deep brain stimulation patterns affect motor symptoms and neural activity in patients with PD, ET, or MS. The goal is to develop more effective DBS treatments by understanding its mechanisms better.

How Is the Trial Designed?

Group I: Therapeutic Stimulation Patterns Experimental Treatment 1 Intervention

This group will receive temporal patterns of stimulation that are designed to suppress oscillatory neural activity at theta- or beta-frequencies. These patterns are hypothesized to alleviate motor symptoms.

Group II: Symptogenic Stimulation Patterns Experimental Treatment 1 Intervention

This group will receive symptogenic patterns of stimulation that are designed to exacerbate oscillatory neural activity at theta- or beta-frequencies. These patterns are hypothesized to exacerbate motor symptoms.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Boston Scientific Corporation

Industry Sponsor

Trials

758

Recruited

867,000+

Michael F. Mahoney

Boston Scientific Corporation

Chief Executive Officer since 2016

MBA from Wake Forest University, BBA in Finance from the University of Iowa

Kenneth Stein

Boston Scientific Corporation

Chief Medical Officer since 2020

MD from Harvard Medical School, MMSc in Clinical Investigation from Harvard-MIT Division of Health Sciences and Technology

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

University of Florida

Collaborator

Trials

1,428

Recruited

987,000+

Published Research Related to This Trial

Temporally Optimized Patterned Stimulation (TOPS) was found to be as effective as standard deep brain stimulation (DBS) in reducing motor symptoms of Parkinson's disease in a study involving 26 subjects, suggesting it could be a viable alternative for symptom relief.

TOPS stimulation patterns, particularly those with low average frequency, not only matched the effectiveness of standard DBS but also reduced estimated energy use, indicating potential for improved energy efficiency in DBS therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporally optimized patterned stimulation (TOPS®) as a therapy to personalize deep brain stimulation treatment of Parkinson's disease. Okun, MS., Hickey, PT., Machado, AG., et al.[2022]

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) 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) is an effective surgical treatment for movement disorders like Parkinson's disease and dystonia, targeting areas such as the subthalamic nucleus (STN) and globus pallidus internus (GPi).

DBS not only improves motor functions but can also affect cognitive and emotional aspects of patients, highlighting the need for careful target selection and consideration of potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical reappraisal of DBS targeting for movement disorders. Guzzi, G., Della Torre, A., Chirchiglia, D., et al.[2017]

Deep brain stimulation (DBS) is effective for treating motor symptoms of Parkinson's disease, particularly when targeting the subthalamic nucleus and globus pallidus internus, which consistently improve motor features.

While some non-motor symptoms also show improvement with DBS, further research is needed to understand these effects better and to explore other deep brain targets like the pedunculopontine nucleus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of motor and non-motor features of Parkinson's disease with deep brain stimulation. Fasano, A., Daniele, A., Albanese, A.[2022]

Deep brain stimulation (DBS) at a therapeutic frequency of 135 Hz significantly alters neuronal activity in the primary motor cortex (M1) of a monkey with Parkinson's disease, leading to improved motor symptoms by changing firing patterns and rates in the pallido-thalamocortical circuit.

Sub-therapeutic DBS (30 Hz) did not enhance motor responses or change discharge rates in M1, indicating that effective symptom relief is linked to specific stimulation parameters that modulate neuronal activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pallidal stimulation that improves parkinsonian motor symptoms also modulates neuronal firing patterns in primary motor cortex in the MPTP-treated monkey. Johnson, MD., Vitek, JL., McIntyre, CC.[2021]

Deep brain stimulation (DBS) is an important treatment option for Parkinson's disease, but estimating the prevalence and categorizing adverse events (AEs) associated with it is challenging due to inconsistent reporting.

The authors advocate for a standardized scheme for reporting AEs related to DBS, which would help in conducting meaningful risk/benefit analyses and assist both physicians and patients in making informed decisions about surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for Parkinson's disease: prevalence of adverse events and need for standardized reporting. Videnovic, A., Metman, LV.[2008]

In a study of 40 Parkinson's disease patients undergoing subthalamic deep brain stimulation (STN-DBS), 45% reported significant improvement in sleep quality at 6 months, although this improvement was not statistically significant at 12 months.

The most common benefits included better overall sleep quality and maintenance, but some patients experienced new-onset daytime sleepiness, indicating that while STN-DBS can improve sleep, the effects can vary widely among individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in Parkinson's disease sleep symptoms and daytime somnolence after bilateral subthalamic deep brain stimulation in Parkinson's disease. Kharkar, S., Ellenbogen, JR., Samuel, M., et al.[2020]

Both 'awake' and 'asleep' deep brain stimulation (DBS) techniques for Parkinson's disease have reliable targeting accuracy for lead placement, ensuring effective treatment.

There are no significant differences in clinical outcomes, costs, or complications between the two DBS techniques, making them equally viable options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Awake and Asleep Deep Brain Stimulation for Parkinson's Disease: A Detailed Analysis Through Literature Review. Wang, J., Ponce, FA., Tao, J., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02553525

Effects of Stimulation Patterns of Deep Brain Stimulation The purpose of this study is to measure the effects of non-regular temporal patterns of deep brain stimulation (DBS) on motor symptoms and neural activity ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30660117/

Long-term outcomes following deep brain stimulation for ... Conclusions: DBS for PD is associated with a 10-year survival rate of 51%. Survey data suggest that while DBS does not halt disease progression ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6295520/

Patterned low-frequency deep brain stimulation induces ... Deep brain stimulation (DBS) is an effective therapy for movement disorders, including Parkinson's disease (PD), although the mechanisms of action remain ...

4. taggs.hhs.gov taggs.hhs.gov/Detail/AwardDetail?arg_AwardNum=R37NS040894&arg_ProgOfficeCode=137

Award Information | HHS TAGGS HHS' Tracking Accountability in Government Grants System (TAGGS) website is a robust reporting tool that displays detailed information on government grants.

5. ctv.veeva.com ctv.veeva.com/study/effects-of-stimulation-patterns-of-deep-brain-stimulation

Effects of Stimulation Patterns of Deep Brain Stimulation These data will guide the design of novel stimulation patterns that may lead to more effective and reliable treatment with DBS. These data ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12439180/

Five-Year Outcomes from Deep Brain Stimulation of the ... This cohort study evaluates 5-year outcomes and safety of subthalamic nucleus deep brain stimulation for the treatment of Parkinson disease.

7. nature.com nature.com/articles/s41467-024-48731-1

Deep brain stimulation of symptom-specific networks in ... Deep Brain Stimulation can improve tremor, bradykinesia, rigidity, and axial symptoms in patients with Parkinson's disease.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3002606/

Deep Brain Stimulation in Parkinson's Disease - PMC In different randomized controlled trials DBS showed a better functional outcome with fewer side effects [Esselink et al. 2004; Schuurman et al. 2000] and ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT07173660

Consensus Statements on Deep Brain Stimulation in ... Deep brain stimulation (DBS) has become a cornerstone therapy for advanced Parkinson's disease (PD), consistently showing superior outcomes over ...