Deep Brain Stimulation for Parkinson's Disease

Recruiting at 1 trial location

Overseen By Svjetlana Miocinovic, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Emory University

Must not be taking: Psychotropic medications

Disqualifiers: Severe tremor, Dementia, Heart disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how deep brain stimulation (DBS) affects thinking and action control in people with Parkinson's Disease. Researchers aim to determine if the location and strength of electrical stimulation can influence brain circuits related to decision-making. Participants may experience various DBS settings or a placebo (inactive treatment) to assess the effects. Those diagnosed with Parkinson's Disease, considering DBS surgery, and able to safely undergo the procedure may be suitable candidates. Additionally, a group of healthy individuals without neuropsychiatric conditions will participate as a comparison group. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective DBS treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial requires participants to temporarily stop taking antiparkinsonian medications for research recordings. If you cannot hold your medications, you may not be eligible to participate.

What is the safety track record for these treatments?

Research shows that deep brain stimulation (DBS) is generally safe for people with Parkinson's disease. DBS has been used for many years to help manage symptoms like tremors and stiffness. Studies have demonstrated that DBS can significantly reduce symptoms and improve quality of life. For instance, a long-term study found that individuals who underwent DBS experienced lasting relief from movement problems even after five years.

When DBS is set to boost activity in the front part of the brain, research suggests it can enhance brain function by altering communication within the brain. This might aid both movement and thinking skills. Another study examined the safety of different DBS methods and found them to be practical and safe.

DBS settings that focus on reducing activity in the front part of the brain are also considered safe. Research supports that this approach can help improve various Parkinson's symptoms, like slow movement and stiffness. However, there might be some effects on thinking skills, such as finding the right words.

Overall, DBS is widely used and well-studied for Parkinson's. It has a good safety record, though, like any procedure, there are risks. It's important to discuss any concerns with a doctor. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it's exploring how different settings of deep brain stimulation (DBS) can affect Parkinson's disease symptoms. Unlike standard treatments like medication, which primarily manage symptoms, DBS has the potential to modify brain activity directly. This trial is testing various DBS settings, including those that maximize or minimize activation of the prefrontal cortex, to see how they influence motor control and cognitive functions. By fine-tuning these settings, the goal is to enhance effectiveness and tailor treatments to individual needs, potentially offering more personalized and effective options for managing Parkinson's disease.

What is the effectiveness track record for deep brain stimulation in treating Parkinson's Disease?

Research has shown that deep brain stimulation (DBS) effectively treats Parkinson's disease. In one study, patients experienced noticeable improvements in symptoms such as tremors and stiffness after receiving DBS. Another study found that DBS aids movement control by targeting specific brain areas. This trial will explore different DBS settings, including those focusing on brain regions involved in planning and decision-making. Evidence supports that DBS can reduce discomfort and enhance the overall quality of life for people with Parkinson's. The treatment is well-researched and approved for Parkinson's, demonstrating strong evidence of its benefits. ^{1 6 7 8 9}

Who Is on the Research Team?

Svjetlana Miocinovic, MD, PhD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for individuals with Parkinson's Disease who are undergoing deep brain stimulation (DBS) implantation. The study aims to understand how different DBS settings affect executive functions involving the prefrontal cortex, particularly action inhibition.

Inclusion Criteria

I have been diagnosed with Parkinson's disease.

Functioning DBS system

I am between 45 and 75 years old.

Exclusion Criteria

Dementia

I have heart disease.

I have health issues that could make surgery risky.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative Assessment

Participants with PD are assessed for motor response inhibition tasks and cortical electrophysiology before DBS surgery

1 month

1 visit (in-person)

Intraoperative Data Collection

Electrocorticography (ECoG) signals are recorded during the surgical procedure to implant DBS leads

Single day

1 visit (in-person, during surgery)

Postoperative Follow-up

Participants are monitored for response inhibition and cortical electrophysiology after DBS implantation

Up to 18 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

• Clinical DBS Setting
• DBS Setting Maximizing Prefrontal Activation
• DBS Setting Minimizing Prefrontal Activation
• Levodopa
• Sham DBS

Trial Overview

The study tests various DBS settings and Levodopa medication on patients' response inhibition. It compares clinical DBS, a setting minimizing prefrontal activation, one maximizing it, and a sham (placebo) procedure to see which has the best impact on executive function.

How Is the Trial Designed?

Group I: Patients with Parkinson's Disease Experimental Treatment 5 Interventions

Patients with PD complete motor response inhibitions tasks under multiple conditions, depending on the study aim they are participating in. Those who are participants in Aim 1 of the study are able to also participate in Aims 2 and 3 if they are having a clinically indicated DBS leads implanted. Patients with PD will participate in the study for approximately 18 months which includes one preoperative visit, intraoperative data collection and two post-operative visits. As part of the motor inhibition tasks, EEG signals will be recorded. A cap similar to a swim cap will be placed on the head of the subject, and gel will be applied to the hair to get a good signal. Electrodes will be attached to the cap for recording of brain signals. A few additional flat electrodes will be placed on the skin to record hand muscle activity (for GNG task) and near the eyes to record eye movements. Accelerometer sensors will be utilized to record arm movements (for MSS task).

Group II: Healthy Controls Active Control 1 Intervention

Healthy participants complete motor response inhibition tasks during two study visits. Healthy controls will participate for approximately one month, which includes two study visits. As part of the motor inhibition tasks, EEG signals will be recorded. A cap similar to a swim cap will be placed on the head of the subject, and gel will be applied to the hair to get a good signal. Electrodes will be attached to the cap for recording of brain signals. A few additional flat electrodes will be placed on the skin to record hand muscle activity (for GNG task) and near the eyes to record eye movements. Accelerometer sensors will be utilized to record arm movements (for MSS task).

Clinical DBS Setting is already approved in European Union, United States, Canada, Japan, China, Switzerland 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

Approved in China as Deep Brain Stimulation for:

• Parkinson's disease

Approved in Switzerland as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Dystonia

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

In a study involving 15 patients with Parkinson's disease, deep brain stimulation (DBS) using a pulse width of 30 µs was found to have a significantly larger therapeutic window compared to 60 µs, meaning it was more effective with fewer side effects.

Both pulse widths were equally effective in improving motor symptoms as measured by the UPDRS III score, but the 30 µs setting was more energy efficient and had a lower risk of stimulation-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulse duration settings in subthalamic stimulation for Parkinson's disease. Steigerwald, F., Timmermann, L., Kühn, A., et al.[2019]

Deep brain stimulation (DBS) of the subthalamic nucleus significantly improves motor symptoms and quality of life in patients with advanced Parkinson's disease, as shown in a study of 47 patients evaluated over 24 months.

The therapy allows for a notable reduction in the dosage of dopaminergic medications, which in turn decreases drug-induced dyskinesias, highlighting its efficacy in managing both symptoms and treatment side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: long-term follow-up. Tavella, A., Bergamasco, B., Bosticco, E., et al.[2013]

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 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 involving 12 Parkinson's disease patients, microelectrode recordings revealed distinct neuronal activity patterns in the subthalamic nucleus (STN), with the dorsal region showing more oscillatory and bursty spike patterns compared to the ventral region, which had irregular firing neurons.

The findings suggest that analyzing spike patterns can help differentiate between the dorsolateral and ventromedial parts of the STN, potentially improving the precision of electrode placement for deep brain stimulation (DBS) and enhancing motor benefits while minimizing cognitive side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative microelectrode recording for the delineation of subthalamic nucleus topography in Parkinson's disease. Seifried, C., Weise, L., Hartmann, R., et al.[2018]

In a study of 26 elderly patients with Parkinson's disease undergoing subthalamic deep brain stimulation (STN-DBS), there was a higher incidence of serious adverse events, particularly psychosis and hallucinations, compared to younger patients from the EARLYSTIM study.

Despite these psychiatric complications being transient, the overall benefits of STN-DBS in improving Parkinson's symptoms were found to outweigh the risks, highlighting the importance of thorough psychiatric evaluations before and after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Older Candidates for Subthalamic Deep Brain Stimulation in Parkinson's Disease Have a Higher Incidence of Psychiatric Serious Adverse Events. Cozac, VV., Ehrensperger, MM., Gschwandtner, U., et al.[2020]

In a study of 17 patients with advanced Parkinson's disease who underwent bilateral deep brain stimulation of the subthalamic nucleus (DBS-STN), there was a significant 45% improvement in motor function as measured by the UPDRS III scale, along with a 24% reduction in levodopa dosage one year post-surgery.

The effectiveness of DBS-STN was found to be related to the internal capsule (IC) stimulation threshold, with lower thresholds (3-7 V) resulting in significantly lower energy consumption compared to higher thresholds (>7 V), indicating that precise electrode placement can enhance both motor outcomes and battery efficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The value of the internal capsule signs in the stimulation of the subthalamic nucleus in Parkinson's disease]. Escamilla, F., Mínguez, A., Jouma-Katati, M., et al.[2013]

In a study of 69 patients with advanced Parkinson's disease who underwent deep brain stimulation (DBS), 53% of those with subthalamic nucleus (STN) stimulation reported ongoing adverse events (AEs) four years post-surgery, compared to 35% in the internal globus pallidus (GPi) group.

Most AEs were not severe and affected cognitive, psychiatric, and motor functions, with a notable correlation between the presence of AEs and longer disease duration and pre-existing gait and psychiatric issues in STN DBS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter study on deep brain stimulation in Parkinson's disease: an independent assessment of reported adverse events at 4 years. Hariz, MI., Rehncrona, S., Quinn, NP., et al.[2008]

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]

Deep brain stimulation (DBS) in the subthalamic nucleus (STN) significantly improved motor function in Parkinson's disease patients, with a notable reduction in the Unified Parkinson's Disease Rating Scale (UPDRS) score from 34.44 to 18.76 over 48 weeks.

The location of the stimulating contact within the STN (medial vs. lateral) did not significantly affect motor outcomes, indicating that the effectiveness of DBS may not depend on the precise placement within the STN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of differential motor outcome with subthalamic nucleus region stimulation in Parkinson's disease. Kasasbeh, A., Abulseoud, OA., Matsumoto, JY., et al.[2015]

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]

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]

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]

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This cohort study evaluates 5-year outcomes and safety of subthalamic nucleus deep brain stimulation for the treatment of Parkinson disease.

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Objective: To evaluate the clinical benefit of stimulating a combination of STN and GP DBS leads and to demonstrate biomarker discovery for ...

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Following six months, subthalamic (STN)-DBS reduced sensory complaints related to parkinsonism and bodily discomfort, increasing central beta-endorphin level.

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This cohort study evaluates 5-year outcomes and safety of subthalamic nucleus deep brain stimulation for the treatment of Parkinson disease.

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clinicaltrials.gov/study/NCT00282152

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Lasting relief of Parkinson's motor symptoms found with DBS

Deep brain stimulation, a surgical procedure known as DBS, provides relief of Parkinson's motor symptoms after five years, per a U.S. study.