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

8 Participants Needed

Trial Summary

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

Research shows that deep brain stimulation (DBS) of the subthalamic nucleus (STN) significantly improves motor function in Parkinson's disease patients, as seen by a reduction in motor symptoms scores. This suggests that STN-PPN DBS Surgery could be effective in managing Parkinson's disease symptoms. ^{1 2 3 4 5}

Is DBS surgery for Parkinson's disease generally safe?

Deep Brain Stimulation (DBS) surgery for Parkinson's disease is generally considered safe, but some patients may experience side effects like confusion, psychiatric issues, or problems with speech and balance. These side effects are more common in older patients and those with longer disease duration. ^{6 7 8 9 10}

How is STN-PPN DBS Surgery different from other treatments for Parkinson's disease?

STN-PPN DBS Surgery is unique because it involves deep brain stimulation (DBS) targeting both the subthalamic nucleus (STN) and the pedunculopontine nucleus (PPN), which may offer benefits in managing motor symptoms and gait issues in Parkinson's disease, unlike traditional DBS that typically targets only the STN. ^{1 11 12 13 14}

What is the purpose of this trial?

This is a mechanistic study to determine the differential effects of the dopaminergic and cholinergic systems on attention, gait, and balance. The primary goal of the study is to evaluate the relative effects of pedunculopontine nucleus (PPN) and subthalamic nucleus (STN) Deep Brain Stimulation (DBS) on these features in persons with Parkinson's Disease (PD) who are eligible for DBS for improvement of their motor symptoms and exhibit gait instability with falls. Patients will be enrolled and implanted with bilateral electrodes in one of the approved DBS locations (subthalamic nucleus: STN), but additionally electrodes will be inserted into the experimental target, namely the PPN bilaterally.

Research Team

Guillermo Moguel-Cobos, MD

Principal Investigator

Muhammad Ali Movement Disorders Clinic Physician

Eligibility Criteria

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.

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

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

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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]

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]

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 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 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 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]

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 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 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]

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]

References

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

Bilateral Subthalamic Nucleus Deep Brain Stimulation in Elderly Patients With Parkinson Disease: A Case-Control Study. [2021]

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

The Role of Levodopa Challenge in Predicting the Outcome of Subthalamic Deep Brain Stimulation. [2023]

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

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

4. Scotland pubmed.ncbi.nlm.nih.gov

Lack of differential motor outcome with subthalamic nucleus region stimulation in Parkinson's disease. [2015]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Long-term Effects of Bilateral Subthalamic Deep Brain Stimulation on Postural Instability and Gait Difficulty in Patients with Parkinson's Disease. [2020]

6. 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]

7. 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]

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. 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]

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. Netherlands pubmed.ncbi.nlm.nih.gov

The Role of Microelectrode Recording in Deep Brain Stimulation Surgery for Parkinson's Disease: A Systematic Review and Meta-Analysis. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

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

13. Thailand pubmed.ncbi.nlm.nih.gov

SW2-year outcomes of subthalamic deep brain stimulation for idiopathic Parkinson's disease. [2022]

14. Netherlands 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. [2023]