Burst-Type Deep Brain Stimulation for Parkinson's Disease

(BURST Trial)

Overseen By Donald Whiting, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Disqualifiers: Cognitive decline, others

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

Compensation: Varies

Number of Visits: 4

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to electrical brain stimulation for people with Parkinson's disease. It compares a standard method with an experimental one that sends bursts of electrical signals to the brain, known as Burst-type Deep Brain Stimulation (Burst-type DBS). Researchers hope this new method could be more effective and longer-lasting. Individuals who have used a specific type of brain device for Parkinson's for at least six months and have not recently changed their treatment might be suitable candidates.

As an unphased trial, this study provides a unique opportunity to explore innovative treatments that could enhance quality of life.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it requires that your Parkinson's disease medications have been stable for at least 6 months before joining.

What prior data suggests that this stimulation protocol is safe for Parkinson's Disease patients?

Research has shown that burst-type deep brain stimulation (DBS) is safe and well-tolerated. This method delivers bursts of electrical pulses, similar to traditional high-frequency ones. Studies have found it not only feasible but also potentially useful for managing symptoms. Participants in these studies did not report any major safety issues, making it a promising option. For those considering a clinical trial, this information suggests that burst-type DBS might be a safe choice. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Burst-type Deep Brain Stimulation (DBS) for Parkinson's Disease because it offers a novel approach to electrical stimulation. Unlike the standard high-frequency DBS, which delivers continuous stimulation, Burst-type DBS uses intermittent bursts of traditional high-frequency rectangular wave stimulation. This new stimulation protocol could potentially enhance therapeutic effects or reduce side effects compared to standard DBS. By exploring this method, researchers hope to improve the quality of life for people with Parkinson's Disease by better managing their symptoms.

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

Research shows that deep brain stimulation (DBS) can help treat movement problems, such as those in Parkinson's disease. This trial will compare two types of DBS programming: standard of care DBS programming and a new type called burst-type DBS, which uses bursts of electrical signals. Early studies suggest that this burst-type method can affect different Parkinson's symptoms in various ways. Some patients have experienced improved movement, which is promising. However, since results vary among individuals, more research is needed to fully understand its effectiveness. Participants in this trial will receive both types of programming in different sequences to evaluate their effectiveness. ^{1 2 4 6 7}

Who Is on the Research Team?

Nestor Tomycz

Principal Investigator

Allegheny Health Network AGH Department of Neuroscience

Are You a Good Fit for This Trial?

This trial is for Parkinson's Disease patients who've had bilateral DBS-STN implants for at least 6 months, can use a DBS controller, and have stable medication and DBS settings. It excludes those with non-Boston scientific Genus/Gevia DBS tech, cognitive decline, or inability to complete follow-ups.

Inclusion Criteria

Comfortable using DBS controller to turn off device prior to study visits

Able to provide informed consent and complete follow-up visits

I have had DBS for Parkinson's in both sides of my brain for at least 6 months.

Exclusion Criteria

I cannot attend all the follow-up visits.

DBS technology other than Boston scientific Genus/Gevia

My DBS targets in the brain are not the STN.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline and Randomization

Participants undergo baseline assessments and are randomized to either burst-type or standard DBS programming

1 day

1 visit (in-person)

Treatment

Participants receive burst-type DBS programming and are evaluated at 6 and 12 months

12 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Burst-type DBS electrical stimulation programming
• Standard of care DBS programming

Trial Overview The study compares burst-type DBS electrical stimulation programming—a new protocol delivering intermittent bursts of stimulation—with the standard continuous high-frequency stimulation in managing Parkinson's symptoms.

How Is the Trial Designed?

Group I: Experimental Burst-type Programming First, Then Baseline Programming Experimental Treatment 2 Interventions

In this arm, patients were randomized to initially receive treatment with experimental Burst-type DBS programming at Visit 1. After a 30 minute treatment period, patients were to undergo UPDRS III evaluation, a 15 minute washout period with the DBS turned off and then baseline programming (standard of care) for 30 minutes. Finally, patients were to undergo UPDRS III evaluation after the second round of programming. Burst-type DBS is defined as a novel stimulation protocol in which intermittent bursts of traditional high-frequency rectangular wave stimulation are delivered.

Group II: Baseline Programming First, Then Experimental Burst-type Programming Experimental Treatment 2 Interventions

In this arm, patients were randomized to initially receive treatment with baseline DBS programming (standard of care) at Visit 1. After a 30 minute treatment period, patients were to undergo UPDRS III evaluation, a 15 minute washout period with the DBS turned off and then experimental Burst-type programming for 30 minutes. Finally, patients were to undergo UPDRS III evaluation after the second round of programming.

Burst-type DBS electrical stimulation programming is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Dystonia

Approved in United States as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Dystonia
• Obsessive-compulsive disorder

Approved in Canada as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Dystonia

Approved in Japan as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor

Who Is Running the Clinical Trial?

Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Lead Sponsor

Trials

52

Recruited

13,000+

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

Published Research Related to This Trial

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]

In a study of 107 patients undergoing Implantable Pulse Generator (IPG) replacement for Deep Brain Stimulation (DBS), a careful surgical technique was employed that successfully avoided errors in lead connection and laterality changes, which are common issues during such procedures.

The mean surgery duration was only 25 minutes, and all patients experienced stable symptoms post-replacement, indicating that with proper management, IPG replacement can be performed safely and effectively without extended hospitalization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to avoid trivial mistakes during IPG replacement in patients treated with DBS for movement disorders: technical note from 13-years experience. Latini, F., Sensi, M., Preda, F., et al.[2015]

In a study involving 28 patients with Parkinson's disease and essential tremor, newer generation deep brain stimulation (DBS) systems showed a significantly greater therapeutic window compared to legacy systems, indicating better control over symptoms with fewer side effects.

Both newer and legacy DBS systems resulted in similar improvements in motor scores and medication reduction after six months, suggesting that while the newer systems offer enhanced programming options, their overall efficacy in symptom management remains comparable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Experience With New Generation Deep Brain Stimulation Leads in Parkinson's Disease and Essential Tremor Patients. Shao, MM., Liss, A., Park, YL., et al.[2022]

Deep brain stimulation (DBS) can significantly improve quality of life in carefully selected patients with Parkinson's disease, even in cases where traditional treatments like levodopa are ineffective.

This case report of a 47-year-old woman with severe, levodopa-unresponsive symptoms shows that with a thorough evaluation and an interdisciplinary approach, DBS can be beneficial for patients with advanced Parkinson's disease, challenging the notion that certain symptoms are absolute contraindications for the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthalamic Nucleus Deep Brain Stimulation in a Patient with Severe Axial Symptoms and Suboptimal Levodopa Responsive Parkinson's Disease. Nassehi, B., Assadnejad, T., Yildiz, O., et al.[2022]

Deep brain stimulation (DBS) for Parkinson's disease is generally safe, with a low mortality rate of 0.2% and permanent morbidity at 0.6%, but complications such as intracerebral hemorrhage (ICH) and seizures can occur in a small percentage of cases.

The study found that the type of lead used in DBS can influence complications, with Medtronic's leads associated with higher rates of perielectrode brain edema compared to Boston Scientific's, highlighting the need for further research on hardware design to improve safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. Servello, D., Galbiati, TF., Iess, G., et al.[2023]

Deep brain stimulation (DBS) is effective for managing parkinsonian symptoms, but in rare cases, it can lead to severe mood disruptions, as demonstrated by a 58-year-old woman who developed rapid-onset depression during a routine battery replacement procedure after 5 years of DBS treatment.

Electroconvulsive therapy (ECT) proved to be an effective treatment for the patient's severe depression, highlighting its potential as a therapeutic option for patients experiencing intractable mood disorders related to DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of electroconvulsive therapy for depression associated with deep brain stimulation in a patient with post-traumatic Parkinson's Disease: a case study. Cunningham, MG., Yadollahikhales, G., Vitaliano, G., et al.[2018]

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 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]

A survey of 298 neurologists revealed that both movement disorders specialists and non-specialists generally agree on the benefits of deep brain stimulation (DBS) for managing advanced Parkinson's disease, although they differ on referring patients with poor responses to levodopa.

Both groups expressed a need for more information regarding the appropriate indications for DBS, potential adverse effects, and postoperative programming, highlighting a gap in knowledge that could impact patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survey of U.S. neurologists' attitudes towards deep brain stimulation for Parkinson's disease. Shih, LC., Tarsy, D.[2022]

A study involving 11 subjects with Parkinson's disease and essential tremor demonstrated that nonconventional deep brain stimulation (DBS) settings, such as narrow pulse widths and square biphasic pulses, were well tolerated and could potentially improve motor outcomes compared to standard settings.

The research indicates that some nonconventional DBS settings may provide similar or even greater benefits without compromising the efficiency of the implantable pulse generators, suggesting that simple firmware upgrades could enhance DBS therapy options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Blinded Pilot Testing of Nonconventional Stimulation Patterns and Shapes in Parkinson's Disease and Essential Tremor: Evidence for Further Evaluating Narrow and Biphasic Pulses. Akbar, U., Raike, RS., Hack, N., et al.[2023]

Adaptive deep brain stimulation (DBS) for Parkinson's disease adjusts stimulation based on the state of neural circuits, specifically targeting bursts of beta activity, which correlates with motor impairment.

This method effectively reduces long-duration beta bursts, potentially making it more effective and selective than conventional DBS, which suppresses beta activity uniformly without addressing burst dynamics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson's disease. Tinkhauser, G., Pogosyan, A., Little, S., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41030401/

Burst-type deep brain stimulation of the subthalamic ... Burst programming provided variable results in therapeutic effect for the patient's bilateral STN DBS of differing Parkinson's phenotypes.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05753449?term=Boston%20Scientific%20Vercise&viewType=Table&rank=9

Burst-Type Deep Brain Stimulation of the Subthalamic ... This is a study to evaluate Deep brain stimulation (DBS) burst-type electrical stimulation programming verses standard DBS programming.

3. surgicalneurologyint.com surgicalneurologyint.com/surgicalint-articles/burst-type-deep-brain-stimulation-of-the-subthalamic-nucleus-in-parkinsons-disease-a-case-series-on-tolerability-and-efficacy/

Burst-type deep brain stimulation of the subthalamic ... Conclusion: Burst programming provided variable results in therapeutic effect for the patient's bilateral STN DBS of differing Parkinson's phenotypes. Further ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12477950/

Burst-type deep brain stimulation of the subthalamic ... Deep brain stimulation (DBS) has become an evidence-based treatment for movement disorders such as Parkinson's disease (PD). Recent animal studies of DBS ...

5. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2021.651168/full

Safety and Tolerability of Burst-Cycling Deep Brain ... Motor and cognitive outcome in patients with Parkinson's disease 8 years after subthalamic implants. Brain J. Neurol. 133, 2664–2676. doi ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05753449

Study Details | Burst-Type Deep Brain Stimulation of the ... This is a study to evaluate Deep brain stimulation (DBS) burst-type electrical stimulation programming verses standard DBS programming. Burst-type DBS is ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33981207/

Safety and Tolerability of Burst-Cycling Deep Brain ... BCDBS was feasible, safe and well tolerated and it has potential to be a viable future DBS programming strategy.