Brain Stimulation for Parkinson's Disease

Recruiting in Palo Alto (17 mi)

Overseen by Darrin Lee, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Southern California

Disqualifiers: Epilepsy, Dementia, Substance abuse

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing whether changing the way the brain is stimulated can improve thinking and movement in people with Parkinson's Disease who already have a brain stimulator. It compares a new type of stimulation (theta burst) with the usual type (gamma). The goal is to see if different electrical impulses can make a difference in brain function. Theta burst stimulation has shown promise in improving motor behavior and synaptic plasticity in experimental parkinsonism.

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 data supports the effectiveness of the treatment STN DBS for Parkinson's Disease?

Research shows that subthalamic nucleus deep brain stimulation (STN DBS) is effective in improving motor symptoms and daily activities in Parkinson's disease patients, with significant reductions in tremors, rigidity, and medication needs. ^{1 2 3 4 5}

Is deep brain stimulation of the subthalamic nucleus safe for humans?

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is generally considered safe for treating Parkinson's disease, with studies showing stable long-term motor responses. However, some patients may experience surgical adverse events or postoperative confusion, highlighting the importance of careful patient selection and monitoring. ^{6 7 8 9 10}

How is the STN DBS - Gamma and Theta Burst treatment for Parkinson's disease different from other treatments?

The STN DBS - Gamma and Theta Burst treatment for Parkinson's disease is unique because it involves deep brain stimulation (DBS) of the subthalamic nucleus (STN), which uses electrical impulses to regulate brain activity. This method is different from traditional drug treatments as it directly targets brain areas responsible for motor symptoms, potentially reducing the need for medications like levodopa and minimizing their side effects. ^{9 11 12 13 14}

Research Team

Darrin Lee, MD

Principal Investigator

University of Southern California, Keck School of Medicine

Eligibility Criteria

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

History of dementia

I have a history of epilepsy or seizures.

Trial Timeline

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

Treatment Details

Interventions

• STN DBS - Gamma (Brain Stimulation)
• STN DBS - Theta Burst (Brain Stimulation)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Dr. Samir A.

University of Southern California

Chief Executive Officer since 2024

PhD in Molecular Biology from the University of Southern California

Dr. Chung

University of Southern California

Chief Medical Officer since 2016

MD from UC San Diego

Findings from Research

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]

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]

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]

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]

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 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 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 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 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]

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]

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]

References

1. Poland pubmed.ncbi.nlm.nih.gov

Subthalamic deep brain stimulation for the treatment of Parkinson disease. [2019]

2. United States 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. [2023]

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

Subthalamic Nucleus Stimulation-Induced Local Field Potential Changes in Dystonia. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Subthalamic Nucleus Deep Brain Stimulation May Reduce Medication Costs in Early Stage Parkinson's Disease. [2018]

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

Improvement of Advanced Parkinson's Disease Manifestations with Deep Brain Stimulation of the Subthalamic Nucleus: A Single Institution Experience. [2020]

6. Spain 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. [2014]

7. Austria 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. [2022]

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

Postoperative Confusion in Patients with Parkinson Disease Undergoing Deep Brain Stimulation of the Subthalamic Nucleus. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the subthalamic nucleus in PD: an analysis of the exclusion causes. [2019]

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

Subthalamic nucleus high-frequency stimulation for advanced Parkinson's disease: motor and neuropsychological outcome after 10 years. [2017]

11. Austria 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. [2019]

12. Turkey pubmed.ncbi.nlm.nih.gov

Manic episode following deep brain stimulation of the subthalamic nucleus for Parkinson's disease: a case report. [2022]

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

Effective deep brain stimulation suppresses low-frequency network oscillations in the basal ganglia by regularizing neural firing patterns. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Urinary profile of catecholamines and metabolites in Parkinson patients with deep brain stimulation. [2015]