Deep Brain Stimulation for Parkinson's Disease

Overseen By Maria Yaroshinsky, BA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must not be taking: Anticoagulants

Disqualifiers: Uncontrolled hypertension, Seizures, Heart disease, others

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

Compensation: Varies

Number of Visits: 7

Duration: 6 months

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a single-center phase I clinical study aiming to improve gait functions in patients with Parkinson's disease (PD) by using adaptive neurostimulation to the pallidum. The investigators will use a bidirectional deep brain stimulation device with sensing and stimulation capabilities to 1) decode the physiological signatures of gait and gait adaptation by recording neural activities from the motor cortical areas and the globus pallidus during natural walking and a gait adaptation task, and 2) develop an adaptive deep brain stimulation (DBS) paradigm to selectively stimulate the pallidum during different phases of the gait cycle and measure improvements in gait parameters. This is the first exploration of network dynamics of gait in PD using chronically implanted cortical and subcortical electrodes. In addition to providing insights into a fundamental process, the proposed therapy will deliver personalized neurostimulation based on individual physiological biomarkers to enhance locomotor skills in patients with PD. Ten patients with idiopathic Parkinson's disease undergoing evaluation for DBS implantation will be enrolled in this single treatment arm study.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have tried oral medications without adequate relief, so it's possible you may continue your current treatment.

Is deep brain stimulation generally safe for humans?

Deep brain stimulation (DBS) is generally considered safe, but it can have complications. Common issues include infections, lead migrations (movement of the wires), and device malfunctions. Serious complications like permanent neurological problems occur in 4-6% of cases, and some patients may need additional surgery to fix issues. ^{1 2 3 4 5}

How is the Summit RC+S treatment for Parkinson's disease different from other treatments?

The Summit RC+S treatment involves deep brain stimulation (DBS), which is a surgical procedure that uses electrical impulses to regulate brain activity, offering an alternative for patients with advanced Parkinson's disease who do not respond well to medication. This treatment is unique because it targets specific brain areas to improve motor symptoms and quality of life, unlike traditional drug therapies. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Summit RC+S for Parkinson's Disease?

Research shows that deep brain stimulation (DBS) significantly improves motor symptoms and daily activities in Parkinson's patients, reducing tremors, rigidity, and medication side effects. This suggests that similar treatments like Summit RC+S could also be effective. ^{6 8 11 12 13}

Who Is on the Research Team?

Doris Wang, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for Parkinson's Disease patients aged 21-75 with motor symptoms for over 3 years, experiencing gait impairments despite medication. They must be able to consent, travel to the study site, recharge the device, and have a significant improvement in their condition on medication. Excluded are those with psychogenic disorders, pregnant women, substance abuse issues, cognitive impairments or allergies to device materials.

Inclusion Criteria

Ability to give informed consent for the study

I or my caregiver can recharge the medical device as needed.

I have chosen to undergo deep brain stimulation surgery for my condition.

Exclusion Criteria

I have had brain surgery before.

I need treatments like ECT, rTMS, or diathermy for my condition.

You have a history of using drugs or alcohol in a harmful way.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation

Participants are implanted with unilateral or bilateral RC+S devices and electrodes

4 weeks

1 visit (in-person)

Treatment

Adaptive and open-loop deep brain stimulation settings are randomized for 30-day periods with motor skill and gait measurements

6 months

Daily tasks at home, periodic in-person assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Regular assessments every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Summit RC+S

Trial Overview The Summit RC+S deep brain stimulation device is being tested on Parkinson's patients to improve walking functions by stimulating the pallidum during different phases of gait. This phase I study records neural activities and aims to personalize neurostimulation based on physiological biomarkers.

How Is the Trial Designed?

Group I: Open-loop deep brain stimulation Active Control 1 Intervention

Parkinson's disease patients implanted with Summit RC+S and brain lead implanted in the pallidal/striatal region receiving open-loop deep brain stimulation.

Group II: Randomized deep brain stimulation Active Control 1 Intervention

Parkinson's disease patients implanted with Summit RC+S and brain lead implanted in the pallidal/striatal region receiving closed-loop stimulation at random time points.

Group III: Deep brain stimulation during contralateral limb movement Active Control 1 Intervention

Parkinson's disease patients implanted with Summit RC+S and brain lead implanted in the pallidal/striatal region receiving closed-loop stimulation during time of contralateral limb movement.

Group IV: Deep brain stimulation during contralateral limb rest Active Control 1 Intervention

Parkinson's disease patients implanted with Summit RC+S and brain lead implanted in the pallidal/striatal region receiving closed-loop stimulation during time of no movement for contralateral limb.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Doris Wang, MD, PhD

Lead Sponsor

Trials

2

Recruited

30+

Michael J. Fox Foundation for Parkinson's Research

Collaborator

Trials

117

Recruited

537,000+

Burroughs Wellcome

Industry Sponsor

Trials

8

Recruited

2,800+

Published Research Related to This Trial

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]

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 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]

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]

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 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]

Deep brain stimulation (DBS) for advanced Parkinson's disease, using Multiple Sequences Image Fusion (MuSIF) for accurate targeting, led to a significant reduction of 76% in L-dopa equivalent daily dose after 3 months.

Patients experienced a 50% reduction in dyskinesias and a 45% decrease in motor fluctuations, demonstrating the efficacy of the combined imaging techniques in improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple sequential image-fusion and direct MRI localisation of the subthalamic nucleus for deep brain stimulation. Rampini, PM., Locatelli, M., Alimehmeti, R., et al.[2017]

Citations

1. 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]

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

Deep Brain Stimulation Impact on Social and Occupational Functioning in Parkinson's Disease with Early Motor Complications. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease. [2015]

4. Germany pubmed.ncbi.nlm.nih.gov

[Deep brain stimulation for Parkinson's disease]. [2021]

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

Insights gleaned by measuring patients' stated goals for DBS: More than tremor. [2022]

6. United States 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Safety considerations for deep brain stimulation: review and analysis. [2007]

8. Austria pubmed.ncbi.nlm.nih.gov

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. [2023]

9. Switzerland 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. [2020]

10. United States 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. [2008]

11. Italy pubmed.ncbi.nlm.nih.gov

Multiple sequential image-fusion and direct MRI localisation of the subthalamic nucleus for deep brain stimulation. [2017]

12. Italy pubmed.ncbi.nlm.nih.gov

Subthalamic nucleus stimulation in Parkinson's disease. [2021]

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

Comparison of subthalamic nucleus deep brain stimulation and Duodopa in the treatment of advanced Parkinson's disease. [2013]