Deep Brain Stimulation for Parkinson's Disease

(MOPSO PIGD Trial)

Overseen By Samantha La Belle, BA

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Minnesota

Disqualifiers: Neurological, Musculoskeletal, Dementia, Pregnancy, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

60 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. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment for Parkinson's Disease?

Research shows that deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is effective in improving motor symptoms in Parkinson's disease patients, with significant improvements in motor function observed in long-term studies. ^{1 2 3 4 5}

Is deep brain stimulation safe for humans?

Deep brain stimulation (DBS) for Parkinson's disease has been studied for safety, with some patients experiencing adverse events (side effects) like changes in thinking, mood, speech, and balance. Most of these side effects were not severe, and they occurred in both types of DBS, targeting different brain areas. ^{1 2 6 7 8}

How is deep brain stimulation different from other treatments for Parkinson's disease?

Deep brain stimulation (DBS) for Parkinson's disease involves placing electrodes in specific brain areas, like the globus pallidus or subthalamic nucleus, to reduce motor symptoms. Unlike medications, DBS provides immediate and sustained relief from motor issues and can be adjusted or reversed if needed, offering a unique approach for patients with severe symptoms. ^{1 2 3 4 9}

What is the purpose of this trial?

Sixty patients will be enrolled in this study who are treated for Parkinson's disease (PD) with bilateral deep brain stimulation of subthalamic nucleus (STN) or globus pallidus (GP), who have a pre- operative 7 Tesla MRI including diffusion tensor imaging for tractography and a postoperative head CT for electrode localization, and in whom at least 3 months have passed since activation of their neurostimulators, for stabilization of clinical stimulator settings. Using their MRI and CT, the investigators will construct patient-specific models of electrical current spread to neuroanatomical tar- gets surrounding the electrode. Then applying nonlinear (particle swarm) optimization, patient- specific stimulator settings will be designed to maximally or minimally activate specific path- ways. In STN DBS: pedunculopallidal vs. pallidopeduncular pathways. In GP DBS: pallidopeduncular pathways at its origin in GP pars interna (GPi) vs. inhibitory afferents to GPi (from GP pars externa GPe). All stimulation falls within the the FDA-approved range for DBS for PD.

Research Team

Scott Cooper, MD, PhD

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for Parkinson's Disease patients with bilateral deep brain stimulation (DBS) who've had a specific type of MRI and CT scan, and have been using their neurostimulators for at least 3 months. It excludes those with dementia, pregnancy, or other conditions affecting movement beyond PD.

Inclusion Criteria

I have had a high-resolution MRI scan before my brain surgery.

I have been diagnosed with Parkinson's disease.

Bilateral DBS

Exclusion Criteria

I have had brain surgery that wasn't for deep brain stimulation.

Dementia

I have a condition that greatly affects my walking, balance, or use of my arms or legs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo DBS stimulation with settings optimized for specific pathways using particle swarm optimization

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• GP DBS
• STN DBS

Trial Overview The study tests personalized stimulator settings in DBS patients to improve gait and balance issues. Using advanced imaging techniques, the trial aims to optimize electrical current delivery to targeted brain areas within approved safety limits.

Participant Groups

Group I: STN DBS Experimental Treatment 1 Intervention

Patients with implanted STN DBS leads will be allocated to this group for DBS stimulation of the STN, within FDA-approved limits and labeling, for symptoms of PD.

Group II: GP DBS Experimental Treatment 1 Intervention

Patients with implanted GP DBS leads will be allocated to this group for DBS stimulation of the GP, within FDA-approved limits and labeling, for symptoms of PD.

GP DBS is already approved in United States, European Union for the following indications:

Approved in United States as GP DBS for:

• Parkinson's disease
• Dyskinesias
• Motor fluctuations

Approved in European Union as GP DBS for:

• Parkinson's disease
• Advanced Parkinson's symptoms
• Motor complications

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

Deep brain stimulation (DBS) for Parkinson's disease can significantly improve motor symptoms, but patients often have unrealistic expectations, leading to dissatisfaction even when clinical improvements are observed.

Postoperative complications, such as worsening speech, gait, and cognition, as well as potential impulse control disorders, highlight the need for careful management and realistic communication about DBS outcomes to enhance patient satisfaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges in PD Patient Management After DBS: A Pragmatic Review. Rossi, M., Bruno, V., Arena, J., et al.[2023]

A patient with Parkinson's disease who had existing bilateral GPi deep brain stimulation (DBS) for dyskinesia underwent additional bilateral STN DBS to address persistent motor fluctuations, which had not improved with GPi stimulation.

The addition of STN DBS successfully increased the patient's 'on' time, reduced her medication needs, and improved her overall motor scores, demonstrating the potential for combined DBS targeting in complex cases of Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral subthalamic deep brain stimulation after bilateral pallidal deep brain stimulation for Parkinson's disease. Deogaonkar, M., Monsalve, GA., Scott, J., et al.[2013]

Deep brain stimulation (DBS) in the subthalamic nucleus (STN) was found to be more effective in reducing Parkinson's disease symptoms compared to stimulation in the globus pallidus internus (GPi), with a significant difference in improvement rates (54.5% vs. 43.1%).

DBS of the GPi was particularly effective in reducing abnormal involuntary movements (AIMs), which were not affected by STN stimulation, suggesting that GPi and STN may have different mechanisms of action in treating Parkinson's symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stimulation of the subthalamic nucleus compared with the globus pallidus internus in patients with Parkinson disease. Peppe, A., Pierantozzi, M., Bassi, A., et al.[2013]

Bilateral high-frequency continuous stimulation of the subthalamic nucleus can effectively replace ineffective globus pallidus stimulation in patients with severe Parkinson's disease, demonstrating a successful alternative treatment.

The study highlights the reversibility of deep brain stimulation therapy, suggesting that targeting the subthalamic nucleus may provide better long-term relief for patients compared to the globus pallidus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Failure of long-term pallidal stimulation corrected by subthalamic stimulation in PD. Houeto, JL., Bejjani, PB., Damier, P., et al.[2019]

In a 5 to 6 year follow-up study of 51 advanced Parkinson's disease patients, both subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) significantly improved motor function, with STN showing a greater improvement of 45.4% compared to 20.0% for GPi.

While both DBS methods improved daily activities and reduced dyskinesias, the STN group experienced more adverse events, suggesting that GPi DBS may be a safer option with fewer complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson's disease. Moro, E., Lozano, AM., Pollak, P., et al.[2023]

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 comparing 128 patients with Parkinson's disease who underwent either GPi or STN deep brain stimulation, no significant differences in cognitive and psychiatric outcomes were observed three years post-surgery, indicating both procedures have similar effects on these aspects.

Measures of social functioning and marital satisfaction were also comparable between the two groups, suggesting that the choice between GPi and STN DBS may not be influenced by cognitive or psychiatric side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive and psychiatric outcome 3 years after globus pallidus pars interna or subthalamic nucleus deep brain stimulation for Parkinson's disease. Boel, JA., Odekerken, VJ., Schmand, BA., et al.[2018]

In a study involving 10 patients with advanced Parkinson's disease, both deep brain stimulation (DBS) of the globus pallidus internus (GPi) and the subthalamic nucleus (STN) showed similar improvements in motor symptoms, with about 40% improvement in Unified PD Rating Scale scores after 12 months.

GPi stimulation was more effective than STN stimulation in improving motor scores when patients were on L-dopa, and it also improved axial symptoms, while STN stimulation reduced the need for L-dopa medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of pallidal and subthalamic nucleus deep brain stimulation for advanced Parkinson's disease: results of a randomized, blinded pilot study. Burchiel, KJ., Anderson, VC., Favre, J., et al.[2022]

Deep brain stimulation (DBS) of both the globus pallidus and subthalamic nucleus provides immediate benefits in reducing motor symptoms of Parkinson's disease, observable as early as 15 minutes after stimulation is turned on.

The effects of DBS are sustained for up to 6 hours, indicating its effectiveness in managing all major motor features of Parkinson's disease in the studied patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect and time course of deep brain stimulation of the globus pallidus and subthalamus on motor features of Parkinson's disease. Hristova, A., Lyons, K., Tröster, AI., et al.[2019]

References

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

Challenges in PD Patient Management After DBS: A Pragmatic Review. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Bilateral subthalamic deep brain stimulation after bilateral pallidal deep brain stimulation for Parkinson's disease. [2013]

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

Stimulation of the subthalamic nucleus compared with the globus pallidus internus in patients with Parkinson disease. [2013]

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

Failure of long-term pallidal stimulation corrected by subthalamic stimulation in PD. [2019]

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

Long-term results of a multicenter study on subthalamic and pallidal stimulation in Parkinson's disease. [2023]

6. 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]

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

Cognitive and psychiatric outcome 3 years after globus pallidus pars interna or subthalamic nucleus deep brain stimulation for Parkinson's disease. [2018]

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

Comparison of pallidal and subthalamic nucleus deep brain stimulation for advanced Parkinson's disease: results of a randomized, blinded pilot study. [2022]

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

Effect and time course of deep brain stimulation of the globus pallidus and subthalamus on motor features of Parkinson's disease. [2019]