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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new form of deep brain stimulation (DBS) to help people with Parkinson's disease improve their walking. Researchers use a special device, called Summit RC+S, to better understand how the brain controls movement and to deliver personalized therapy. The study explores different stimulation approaches based on movement patterns to determine the most effective method. Individuals who have had Parkinson's for at least three years and struggle with walking despite medication might be suitable candidates for this trial.

As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research and potentially benefit from advancements in personalized therapy.

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.

What prior data suggests that this device is safe for improving gait functions in Parkinson's disease patients?

Research has shown that deep brain stimulation (DBS) is generally safe and well-tolerated for people with Parkinson's disease. Studies have found open-loop DBS to be effective without causing major side effects. Adaptive DBS, which adjusts stimulation based on the patient's needs, is also considered safe.

Early results for closed-loop DBS, which automatically changes stimulation in response to brain activity, suggest it is both effective and safe. Specifically, one study found this method more efficient than traditional approaches, with no significant negative effects reported.

Overall, evidence suggests that these DBS treatments are well-tolerated by patients and usually do not lead to serious side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for Parkinson's disease because they explore different methods of deep brain stimulation (DBS) using the Summit RC+S device. Unlike standard DBS treatments that typically deliver constant stimulation, these investigational approaches include open-loop stimulation and various closed-loop strategies. Closed-loop systems adjust stimulation in real-time, either at random, during movement, or during rest, potentially offering more personalized and effective symptom management. By tailoring the stimulation to the patient's specific needs, these treatments could improve motor control and quality of life for those with Parkinson's disease.

What evidence suggests that this trial's treatments could be effective for improving gait in Parkinson's disease?

Research has shown that deep brain stimulation (DBS) effectively treats advanced Parkinson's disease. Studies have found that DBS targeting specific brain areas, such as the globus pallidus pars interna (GPi) and the subthalamic nucleus (STN), provides similar relief from Parkinson's symptoms. In this trial, participants will be assigned to different treatment arms. One arm involves open-loop DBS, which significantly improved patients' waking hours without troublesome movement issues, increasing from about 32% before treatment to around 96% after a year. Other arms will explore adaptive or closed-loop DBS, which adjusts stimulation based on brain activity. Although research on closed-loop DBS is still developing, it aims to customize treatment for each patient, potentially enhancing walking and reducing movement problems. ^{1 2 6 7 8}

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

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

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

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) 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]

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]

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 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]

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]

Citations

1.

brainstimjrnl.com

brainstimjrnl.com/article/S1935-861X(23)00325-X/fulltext

Chronic dual target continuous and externally controlled ...

Percent of waking ON time per day without troublesome dyskinesia improved from preop [32.1% (5.4%,43.8%)] to 1-year [95.8% (89.7%,100%)]. aDBS showed similar ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9514741/

Initial Clinical Outcome With Bilateral, Dual-Target Deep ...

Clinical trials have demonstrated that subthalamic nucleus (STN) and globus pallidus pars interna (GPi) produce equivalent symptom relief. Dual ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04675398

Adaptive Deep Brain Stimulation to Improve Motor and Gait ...

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 ...

4.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/35383660/

Initial Clinical Outcome With Bilateral, Dual-Target Deep Brain ...

Background: Deep brain stimulation (DBS) is an effective therapy in advanced Parkinson disease (PD). Although both subthalamic nucleus (STN) and ...

5.

frontiersin.org

frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2021.714256/full

Analysis-rcs-data: Open-Source Toolbox for the Ingestion, ...

Closed-loop neurostimulation is a promising therapy being tested and clinically implemented in a growing number of neurological and psychiatric indications.

6.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1935861X19300737

Dual threshold neural closed loop deep brain stimulation in ...

This is the first study to demonstrate that STN NclDBS is feasible, efficacious and more efficient than olDBS in tremor and bradykinesia dominant PD patients.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8312257/

Analysis-rcs-data: Open-Source Toolbox for the Ingestion, ...

The Summit RC+S system consists of two surface or depth leads that are implanted in the brain and a neurostimulator (INS) implanted in the chest. The system is ...

8.

academic.oup.com

academic.oup.com/braincomms/article/7/4/fcaf266/8193943

Beta burst-driven adaptive deep brain stimulation for gait ...

Testing was considered safe and tolerable if aDBS did not cause adverse effects that resulted in the participant being unable to tolerate the experiment.