DBS Surgery for Parkinson's Disease

(PPNGB01 Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: St. Joseph's Hospital and Medical Center, Phoenix

Must be taking: Levodopa

Disqualifiers: Dementia, Schizophrenia, Seizure disorder, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new surgical treatment for individuals with Parkinson's Disease who struggle with walking or balance, sometimes resulting in falls. The study compares different types of brain stimulation to determine which most effectively improves attention, walking, and balance. Participants will undergo surgery to implant devices that stimulate specific brain areas. Ideal candidates have had a Parkinson's diagnosis for at least four years, respond well to levodopa medication, and experience issues such as tremors, balance problems, or falls.

As an unphased trial, this study provides participants the chance to contribute to groundbreaking research that could enhance treatment options for Parkinson's Disease.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the study involves deep brain stimulation for Parkinson's Disease, it's possible that some medication adjustments might be necessary. Please consult with the study team for specific guidance.

What prior data suggests that this DBS surgery is safe for Parkinson's Disease patients?

Research has shown that Deep Brain Stimulation (DBS) targeting specific brain areas, such as the pedunculopontine nucleus (PPN) and subthalamic nucleus (STN), is generally safe for people with Parkinson's Disease. When correctly targeting the PPN, DBS can help reduce falls and improve walking, indicating good tolerance of the treatment. Additionally, DBS of the PPN does not appear to affect cognitive abilities, which is a positive safety indicator.

Previous patients have demonstrated that DBS can effectively ease symptoms like tremors and muscle stiffness in Parkinson's Disease. Patient reports suggest that the STN-PPN DBS treatment is safe when performed correctly. While any surgery carries risks, the evidence so far supports the safety of this treatment approach. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the potential benefits of combining STN (subthalamic nucleus) and PPN (pedunculopontine nucleus) deep brain stimulation (DBS) for Parkinson's disease, a new approach that could enhance symptom management. While current DBS treatments typically involve stimulating only the STN, this trial investigates the addition of PPN stimulation, which is believed to play a role in gait and postural control. By using a crossover design with alternating PPN stimulation, researchers aim to uncover whether this dual-targeted approach offers superior results compared to the traditional STN-only DBS, potentially leading to improved mobility and quality of life for patients.

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

This trial will compare two approaches to Deep Brain Stimulation (DBS) for Parkinson's Disease. Participants in one arm will receive STN-PPN DBS, targeting both the subthalamic nucleus (STN) and the pedunculopontine nucleus (PPN). Studies have shown that DBS targeting the STN can improve movement problems in people with Parkinson's Disease. Research also suggests that DBS in the PPN might aid walking and reduce fall risk, although results can vary. Specifically, one study found that using DBS on both sides of the PPN improved movement scores by 45% in some patients. Participants in the other arm will receive traditional STN DBS. While DBS can help with certain symptoms, it may not significantly improve balance issues in PD patients. Overall, DBS can effectively reduce some symptoms of Parkinson's Disease. ^{1 2 3 6 7}

Who Is on the Research Team?

Guillermo Moguel-Cobos, MD

Principal Investigator

Muhammad Ali Movement Disorders Clinic Physician

Are You a Good Fit for This Trial?

This trial is for people aged 18-75 with Parkinson's Disease stages 2-3, who have trouble walking and balancing despite taking Levodopa. They must be able to walk a bit without help, speak English, and be fit for surgery. Pregnant women or those with implanted devices like pacemakers can't join.

Inclusion Criteria

I can walk by myself for short periods.

My Parkinson's is stage 2-3, worsens when I move, and doesn't improve with my current medication.

You are eligible for treatment that targets a specific part of the brain called the STN, according to a group of experts.

Exclusion Criteria

I need specific treatments like rTMS or ECT for my condition.

You have a medical device implanted in your body, such as a pacemaker or neurostimulator.

I have a history of seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Recovery

Participants are implanted with bilateral electrodes in the PPN and STN, followed by initial recovery and mapping visits

3 months

Multiple visits for surgery and mapping

Crossover Treatment

Participants undergo a crossover between PPN stimulation and no stimulation

12 months

Regular follow-up visits

Extended Treatment

Participants receive continuous stimulation from 15 to 27 months post-op

12 months

Regular follow-up visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• STN-PPN DBS Surgery

Trial Overview The study tests how Deep Brain Stimulation (DBS) at two brain sites affects attention, gait, and balance in Parkinson's patients. Participants will get electrodes in the subthalamic nucleus (STN) and an experimental site called the pedunculopontine nucleus (PPN).

How Is the Trial Designed?

Group I: STN-PPN DBS Experimental Treatment 1 Intervention

Patients will be implanted with both bilateral STN and bilateral PPN devices. These patients will undergo a crossover between 3 and 15 months post-op in which they will double-blindly receive PPN stimulation for six months and have stimulation turned off for six months. All patients will receive stimulation from 0-3 months post-op (mapping visits occur in this window) and from 15-27 months.

Group II: STN DBS Active Control 1 Intervention

Subjects will receive traditional bilateral STN devices and stimulation.

Who Is Running the Clinical Trial?

St. Joseph's Hospital and Medical Center, Phoenix

Lead Sponsor

Trials

69

Recruited

17,400+

Arizona State University

Collaborator

Trials

311

Recruited

109,000+

Published Research Related to This Trial

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]

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]

Subthalamic nucleus deep brain stimulation (STN DBS) is safe and effective for improving motor function in patients aged 75 and older, showing similar benefits to younger patients after one year.

Both older and younger cohorts experienced significant improvements in motor function as measured by the Unified Parkinson Disease Rating Scale (UPDRS III), with low complication rates and no significant difference in outcomes between the two age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral Subthalamic Nucleus Deep Brain Stimulation in Elderly Patients With Parkinson Disease: A Case-Control Study. Mitchell, KT., Younce, JR., Norris, SA., et al.[2021]

This study involved 30 Parkinson's disease patients and explored how magnetoencephalography (MEG) can help identify the best stimulation contact point in deep brain stimulation (DBS) of the subthalamic nucleus (STN) by measuring changes in brain activity.

Results showed that more dorsolateral stimulation led to lower low-beta power in the motor cortex, while ventromedial stimulation increased whole-brain delta and theta power, indicating that the contact point affects brain activity, but individual responses varied significantly, making it unclear if MEG can reliably guide optimal DBS settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetoencephalography to measure the effect of contact point-specific deep brain stimulation in Parkinson's disease: A proof of concept study. Boon, LI., Potters, WV., Hillebrand, A., et al.[2023]

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 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 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8568957/

Comparison of the Efficacy of Deep Brain Stimulation in ... Conclusion: The meta-analysis results show that both the STN-DBS and GPi-DBS can affect certain aspects of PD gait disorder. Keywords: ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6448144/

Targeting the Pedunculopontine Nucleus in Parkinson's disease conclude that despite the variation in outcomes, when properly positioned, PPN DBS has the potential to reduce falls and improve gait in PD patients.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1878875024005837

Effectiveness of Deep Brain Stimulation in Improving ... Current research suggests that DBS results in no significant improvement in balance dysfunction for people with PD.

4. academic.oup.com academic.oup.com/brain/article/130/6/1596/292244

Bilateral deep brain stimulation of the pedunculopontine and ... Bilateral PPN-DBS at 25 Hz in OFF-medication produced an immediate 45% amelioration of the motor Unified Parkinson's Disease Rating Scale (UPDRS) subscale score ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04605263

Deep Brain Stimulation (DBS) of the Pedunculopontine ... The primary goal of the study is to evaluate the relative effects of pedunculopontine nucleus (PPN) and subthalamic nucleus (STN) Deep Brain Stimulation (DBS) ...

6. nature.com nature.com/articles/s41467-024-48731-1

Deep brain stimulation of symptom-specific networks in ... Deep Brain Stimulation can improve tremor, bradykinesia, rigidity, and axial symptoms in patients with Parkinson's disease.

7. sciencedirect.com sciencedirect.com/science/article/pii/S259011251930012X

The effects of deep brain stimulation ... The results indicate that PPN-DBS is generally safe from a cognitive perspective. Abstract. Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) ...