Brain Stimulation for Parkinson's Disease

Overseen By Wooseong Choi, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Southern California

Disqualifiers: Epilepsy, Dementia, Substance abuse

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

Compensation: Varies

Number of Visits: 7

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adjusting brain stimulation settings can improve thinking and memory in people with Parkinson's Disease (PD) who already have a deep brain stimulator. Participants will have their device settings changed and will take tests to assess cognitive improvement. They will also undergo fMRI scans (a type of brain imaging) at various times to track changes. Ideal participants already have a deep brain stimulator implanted, have maintained a stable medication routine for at least three months, and can attend all study appointments. As an unphased trial, this study allows participants to contribute to innovative research that could enhance cognitive outcomes for individuals with Parkinson's Disease.

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

The trial does not specify if you need to stop your current medications, but it requires that your medication regimen has been stable for at least 3 months before joining.

What prior data suggests that this brain stimulation technique is safe for people with Parkinson's Disease?

Studies have shown that both Gamma and Theta Burst deep brain stimulation (DBS) for Parkinson's disease are generally well-tolerated by patients. Research indicates that using both theta and gamma frequency stimulation together can improve verbal skills without worsening movement problems or causing safety issues.

Past data suggests that Theta Burst stimulation can be administered safely and might even aid in movement and cognitive function. Patients who received Theta Burst DBS did not report major side effects, indicating it is a safe option for those with Parkinson's.

Although the studies don't provide extensive details on side effects, the absence of reported safety problems is reassuring. Overall, the evidence suggests that both Gamma and Theta Burst DBS are safe for people with Parkinson's. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the brain stimulation techniques, STN DBS - Gamma and STN DBS - Theta Burst, for Parkinson's disease because they offer a novel approach compared to the standard deep brain stimulation (DBS). Traditional DBS targets the subthalamic nucleus (STN) with a constant electrical pulse, but these new methods explore different frequencies and patterns. The Gamma stimulation uses a high-frequency pattern, while Theta Burst uses a patterned burst of stimulation, which may enhance the brain's natural rhythms and improve motor symptoms more effectively. This could potentially lead to better symptom control with fewer side effects, providing a more refined and personalized treatment option for Parkinson's patients.

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

Research shows that deep brain stimulation (DBS) in a specific brain area can improve movement problems in people with Parkinson's disease. In this trial, participants will receive one of two types of DBS. One type, called STN DBS - Gamma, boosts movement by affecting certain brain waves known as gamma oscillations. Studies have detected these brain waves in many patients receiving this treatment.

Another type, STN DBS - Theta Burst, is under study for its potential to improve both movement and thinking skills. Some research suggests it can enhance working memory, which is important for tasks like problem-solving and decision-making. Both types of stimulation show promise, but they work in slightly different ways to address Parkinson's symptoms. ^{2 3 6 7 8}

Who Is on the Research Team?

Darrin Lee, MD

Principal Investigator

University of Southern California, Keck School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Parkinson's Disease who already have a deep brain stimulator implanted. They must be on stable medication for at least three months and able to consent and follow the study plan. People with epilepsy, dementia, or major substance abuse history cannot join.

Inclusion Criteria

Able to comply with all testing, follow-ups and study appointments and protocols

I understand the study and can sign the consent form.

I have had deep brain stimulation implants in both sides of my brain.

Exclusion Criteria

History of major substance abuse

I have a history of epilepsy or seizures.

History of dementia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline assessment under baseline stimulation parameters, including motor and cognitive tests

1 week

1 visit (in-person)

Acute Phase

Randomized double-blind crossover study with theta burst and baseline stimulation settings, including motor and neuropsychological testing

3 weeks

3 visits (in-person)

Chronic Phase

Patients undergo chronic phase with randomized stimulation settings, including repeat neuropsychological and motor testing

6 months

2 visits (in-person)

Open-label Extension

Patients placed on open-label theta burst stimulation for 6 months, with repeat neuropsychological and motor testing

6 months

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• STN DBS - Gamma
• STN DBS - Theta Burst

Trial Overview The study tests if changing how the brain stimulator works can improve thinking skills in Parkinson's patients. It involves two types of stimulation (Theta Burst and Gamma) and checks their effects using cognitive tests and fMRI scans at different times.

How Is the Trial Designed?

Group I: Group B Experimental Treatment 2 Interventions

double blinded randomization into baseline stimulation followed by theta burst stimulation

Group II: Group A Experimental Treatment 2 Interventions

double-blinded randomization into theta burst stimulation followed by baseline stimulation

STN DBS - Gamma is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as STN DBS for:

• Parkinson's disease
• Essential tremor
• Dystonia

Approved in United States as STN DBS for:

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

Approved in Canada as STN DBS for:

• Parkinson's disease
• Essential tremor
• Dystonia

Approved in Japan as STN DBS for:

• Parkinson's disease
• Essential tremor

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Published Research Related to This Trial

In a study of 10 patients with advanced Parkinson's disease, deep brain stimulation (DBS) of the sub-thalamic nucleus significantly improved motor symptoms, as shown by a decrease in the Unified Parkinson's Disease Rating Scale (UPDRS) scores after surgery.

The procedure, performed under general anesthesia using advanced 3D fluoroscopy, resulted in a reduction of L-Dopa medication dosage and had a low complication rate, with only two minor issues reported, suggesting a safe and effective approach to DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

STN DBS for Parkinson's disease: results from a series of ten consecutive patients implanted under general anaesthesia with intraoperative use of 3D fluoroscopy to control lead placement. Delavallée, M., Delaunois, J., Ruwet, J., et al.[2019]

In a study of 233 Parkinson's Disease patients who underwent Deep Brain Stimulation (DBS) of the subthalamic nucleus, only 11.76% of procedures resulted in surgical adverse events (SAEs), indicating a relatively low risk associated with the procedure.

Most SAEs were reversible, with only two cases leading to long-term effects, demonstrating that STN DBS is a safe surgical option with a high reliability rate of 95.59% for correct lead implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical adverse events of deep brain stimulation in the subthalamic nucleus of patients with Parkinson's disease. The learning curve and the pitfalls. Seijo, F., Alvarez de Eulate Beramendi, S., Santamarta Liébana, E., et al.[2022]

In a 10-year follow-up study of 26 Parkinson's disease patients who underwent subthalamic nucleus deep brain stimulation (STN DBS), significant initial improvements in motor function were observed, with a notable reduction in medication dosage.

However, after 5 years, patients experienced a decline in motor performance, particularly in bradykinesia and axial symptoms, while cognitive function showed a decline after the first year, indicating that long-term outcomes may not be as favorable as short-term results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthalamic nucleus high-frequency stimulation for advanced Parkinson's disease: motor and neuropsychological outcome after 10 years. Janssen, ML., Duits, AA., Turaihi, AH., et al.[2017]

In a study of 98 patients with advanced Parkinson's disease, 29.6% were deemed unsuitable for Deep Brain Stimulation (DBS) surgery, highlighting the need for careful patient selection.

The most common reasons for exclusion included neuropsychological disorders (48.3%) and insufficient motor disability (37.9%), indicating that both mental health and the severity of physical symptoms are critical factors in determining candidacy for DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the subthalamic nucleus in PD: an analysis of the exclusion causes. Lopiano, L., Rizzone, M., Bergamasco, B., et al.[2019]

In a study of 23 Parkinson's disease patients undergoing deep brain stimulation of the subthalamic nucleus (DBS-STN), urinary excretion of L-DOPA decreased significantly by about 60% one week after surgery, indicating a reduced need for levodopa medication.

The increase in the dopamine to L-DOPA ratio after DBS-STN suggests that the procedure may enhance the efficacy of oral levodopa, potentially leading to better management of Parkinson's symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary profile of catecholamines and metabolites in Parkinson patients with deep brain stimulation. Guimarães, J., Vieira-Coelho, MA., Moura, E., et al.[2015]

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with advanced Parkinson's disease showed significant long-term motor improvement, with a 66% enhancement in motor function maintained five years post-surgery.

While STN-DBS effectively improved motor symptoms, there was a notable decline in axial symptoms and an increase in dementia cases over five years, suggesting that while DBS is beneficial for motor control, its long-term effects on cognitive health and axial symptoms require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the subthalamic nucleus in advanced Parkinson's disease: five year follow-up at a Portuguese center. Monteiro, A., Andrade, C., Rosas, MJ., et al.[2014]

In a study of 49 patients with Parkinson's disease who underwent deep brain stimulation (DBS) surgery, 26.5% experienced postoperative confusion, highlighting a notable risk associated with this treatment.

The analysis revealed that a higher Charlson comorbidity index, which indicates the presence of other health conditions, was significantly linked to the development of confusion after surgery, suggesting that patients with more health issues may be at greater risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative Confusion in Patients with Parkinson Disease Undergoing Deep Brain Stimulation of the Subthalamic Nucleus. Paim Strapasson, AC., Martins Antunes, ÁC., Petry Oppitz, P., et al.[2019]

In a study of 66 patients with Parkinson's disease treated with subthalamic nucleus deep brain stimulation (STN DBS), there was a significant average reduction of 45% in motor symptoms as measured by the UPDRS III score six months post-implantation.

STN DBS also led to a notable decrease in levodopa consumption, with reductions ranging from 15% to 100%, indicating its potential to enhance treatment efficacy while possibly reducing medication dependency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthalamic deep brain stimulation for the treatment of Parkinson disease. Mandat, T., Tykocki, T., Koziara, H., et al.[2019]

In a study involving 7 patients with craniocervical dystonia, subthalamic nucleus (STN) stimulation did not show significant theta power at rest, but it did induce similar spectral changes as seen in Parkinson's disease, such as broadband power suppression and evoked resonant neural activity.

The findings suggest that STN stimulation produces a non-disease-specific response to high-frequency stimulation, indicating its potential as a treatment option for various disorders characterized by excessive oscillatory activity in the STN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthalamic Nucleus Stimulation-Induced Local Field Potential Changes in Dystonia. Wiest, C., Morgante, F., Torrecillos, F., et al.[2023]

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can lead to psychiatric adverse effects, such as manic episodes with psychotic symptoms, in patients with Parkinson's disease, as demonstrated in two reported cases.

These psychiatric effects may be linked to the stimulation's impact on limbic connections and specific brain oscillations, or the activation of the medial forebrain bundle, highlighting the need for careful monitoring of mood changes in patients undergoing DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manic episode following deep brain stimulation of the subthalamic nucleus for Parkinson's disease: a case report. Ugurlu, TT., Acar, G., Karadag, F., et al.[2022]

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus effectively reverses motor symptoms in a rat model of Parkinson's disease, while low-frequency stimulation does not improve symptoms and may worsen them.

The mechanism behind the effectiveness of high-frequency DBS involves its ability to reduce harmful low-frequency oscillations in neuronal activity and promote a more regular firing pattern in the basal ganglia, rather than simply increasing the firing rate of neurons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective deep brain stimulation suppresses low-frequency network oscillations in the basal ganglia by regularizing neural firing patterns. McConnell, GC., So, RQ., Hilliard, JD., et al.[2021]

Patients with Parkinson's disease who underwent deep brain stimulation (STN-DBS) experienced improved motor function and reduced medication dosage in the first year after surgery, while nonmotor symptoms and cognition remained stable.

STN-DBS patients had a delayed onset of morbidity milestones (like falls and dementia) compared to those receiving medical treatment alone, suggesting that while they may live longer with the disease, significant health declines occur in the last 5 years of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morbidity Milestones Demonstrate Long Disability-Free Survival in Parkinson's Disease Patients with Deep Brain Stimulation of the Subthalamic Nucleus. Schnalke, N., Konitsioti, A., Frank, A., et al.[2023]

Subthalamic nucleus deep brain stimulation (STN-DBS) in early stage Parkinson's disease significantly reduced medication costs by 16% over 24 months, while optimal drug therapy (ODT) costs increased by 72%, leading to a cumulative savings of $7,150 for the DBS group.

Patients receiving STN-DBS were 80% less likely to require multiple medications (polypharmacy) compared to those on ODT, suggesting that DBS can simplify treatment regimens and potentially lead to substantial long-term savings of $64,590 over 10 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthalamic Nucleus Deep Brain Stimulation May Reduce Medication Costs in Early Stage Parkinson's Disease. Hacker, ML., Currie, AD., Molinari, AL., et al.[2018]

In a study of 20 patients with advanced Parkinson's disease, deep brain stimulation (DBS) of the subthalamic nucleus (STN) led to significant improvements in motor symptoms, with a 49.3% reduction in the Unified Parkinson's Disease Rating Scale (UPDRS) scores in the 'off' medication state after one year.

DBS also enhanced daily living activities by 73.8%, reduced the need for medication by 54.1%, and decreased complications like dyskinesia and motor fluctuations, indicating its efficacy in managing Parkinson's disease symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of Advanced Parkinson's Disease Manifestations with Deep Brain Stimulation of the Subthalamic Nucleus: A Single Institution Experience. Rabie, A., Verhagen Metman, L., Fakhry, M., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40322847/

Theta-Gamma Subthalamic Stimulation for Verbal Fluency ... High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves Parkinson's disease (PD) motor symptoms but may deteriorate verbal fluency ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9171607/

Deep brain stimulation in the subthalamic nucleus for ... Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is highly effective for treating the motor symptoms of Parkinson's disease (PD).

3. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25000130

Deep brain stimulation-entrained gamma oscillations in ... Cortical entrained gamma oscillations were detected in 4/5 hemispheres undergoing pallidal stimulation and 12/15 hemispheres undergoing subthalamic stimulation.

4. nature.com nature.com/articles/s41467-025-58132-7

Gamma entrainment induced by deep brain stimulation as ... Here, we investigate the DBS-induced 1:2 gamma entrainment in subthalamic recordings in a large cohort of 19 patients with Parkinson's disease.

5. movementdisorders.onlinelibrary.wiley.com movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.30218

Theta‐Gamma Subthalamic Stimulation for Verbal Fluency in ... High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves Parkinson's disease (PD) motor symptoms but may ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40952750/

Five-Year Outcomes from Deep Brain Stimulation of the ... Although STN-DBS outcomes declined slightly, possibly due to the progressive nature of the disease, patients with PD sustained significant ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1053811925004586?via%3Dihub

Subthalamic nucleus stimulation at high and low ... Subthalamic nucleus (STN) deep brain stimulation (DBS) is used to treat Parkinson's disease (PD), yet neither high-frequency stimulation (HFS) nor low ...

8. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/1107940

Ten-Year Outcome of Subthalamic Stimulation in ... Objective To assess the 10-year motor outcome of deep brain stimulation of the subthalamic nucleus (STN-DBS) in patients with Parkinson disease ...