Subcortical Stimulation for Parkinson's Disease

Overseen By Nader Pouratian, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Must be taking: L-dopa

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Amnestic cognitive deficits, others

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

Compensation: Varies

Number of Visits: Unknown

125 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients should not have used anticoagulant or antiplatelet agents within one week before the trial.

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

Research shows that stimulating a specific brain area called the subthalamic nucleus can significantly improve daily living activities and motor skills in people with advanced Parkinson's disease, with improvements lasting for several months. ^{1 2 3 4 5}

Is subcortical stimulation safe for humans?

Subcortical stimulation, specifically deep brain stimulation of the subthalamic nucleus, is generally considered safe for treating Parkinson's disease, but it can have side effects like depression, speech issues, and balance problems. These side effects are usually mild and temporary, but serious psychiatric issues have been reported, especially in older patients. ^{6 7 8 9 10}

How does subcortical stimulation differ from other treatments for Parkinson's disease?

Subcortical stimulation, specifically targeting the subthalamic nucleus, is unique because it involves implanting electrodes in the brain to deliver electrical impulses, which can significantly improve motor symptoms in Parkinson's disease. Unlike medications that increase dopamine levels, this treatment directly modulates brain activity, offering an alternative for patients with severe symptoms who do not respond well to drugs. ^{1 5 11 12 13}

What is the purpose of this trial?

Humans can rapidly regulate actions according to evolving environmental demands, however, impairments of action regulation have been identified across a number of neurological disorders including Parkinson's Disease (PD). A key component of action regulation is action inhibition that occurs when stopping unwanted or inappropriate actions. There is mounting evidence that action inhibition also plays a critical part in selecting between competing alternative actions and switching to new actions in response to environmental changes. The investigators hypothesize that stop circuitry (involving frontal-subthalamic nucleus (STN) pathways) are involved in inhibiting unselected actions during action selection with competing alternatives (in the absence of overt stopping) and that switching motor plans also engages stopping circuitry (involving prefrontal-STN pathways) for cancelling the ongoing action, before changing to new one. The overall goal is to delineate the neural circuitry underlying a broad array of action regulation functions that involve inhibitory control, how these functions interrelate, and how they are implemented within brain networks. In this research, the investigator will take advantage of the unique opportunity provided by awake deep brain stimulation surgery to learn more about how the brain functions in a diseased state and how deep brain stimulation changes these networks to make movement more normal. The investigator will simultaneously assess cortical and subcortical electrophysiology in relation to clinical symptoms and behavioral measures and in response to deep brain stimulation in patients undergoing Deep Brain Stimulation (DBS) implantation surgery.

Eligibility Criteria

This trial is for adults over 18 with Parkinson's disease, specifically those who respond to L-dopa treatment and are set to undergo deep brain stimulation surgery. Participants should be able to cooperate during an awake surgical procedure.

Inclusion Criteria

I have Parkinson's disease with symptoms like tremor or stiffness.

I am approved for deep brain stimulation surgery.

My Parkinson's symptoms improve significantly when I take my medication.

Exclusion Criteria

I have used blood thinners or anti-clotting medications in the last week.

Neurocognitive testing indicating amnestic cognitive deficits (MOCA < 24)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intra-operative Assessment

Participants undergo deep brain stimulation surgery and complete behavioral assessments while receiving subcortical DBS stimulation. Cortical ECoG and subcortical LFP recordings are conducted.

Intra-operative

Follow-up

Participants are monitored for safety and effectiveness after the surgery and assessments

4 weeks

Treatment Details

Interventions

• Subcortical Stimulation

Trial Overview The study investigates how the brain controls actions in people with Parkinson's by recording brain activity during subcortical stimulation in a conscious state during deep brain stimulation surgery.

Participant Groups

Group I: Parkinson's disease patients Experimental Treatment 1 Intervention

This group consists of Parkinson's disease patients who are undergoing deep brain stimulation surgery for treatment of their movement disorder. Participants will complete behavioral assessments while receiving subcortical DBS stimulation.

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Cedars-Sinai Medical Center

Collaborator

Trials

523

Recruited

165,000+

Findings from Research

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]

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]

The study involved 20 patients with Parkinson's disease and 20 healthy controls, using deep brain stimulation to explore how different pathways in the brain affect motor control and cognitive adaptation during movement tasks.

Findings indicate that while deep brain stimulation can modulate motor functions, it does not fully restore cognitive flexibility or kinematic control, suggesting that targeted stimulation strategies could enhance treatment efficacy and reduce side effects in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional segregation of basal ganglia pathways in Parkinson's disease. Neumann, WJ., Schroll, H., de Almeida Marcelino, AL., et al.[2019]

References

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

Low-frequency subthalamic nucleus stimulation in Parkinson's disease: a randomized clinical trial. [2022]

2. China pubmed.ncbi.nlm.nih.gov

Subthalamic nucleus deep brain stimulation for Parkinson's disease: evidence for effectiveness and limitations from 12 years' experience. [2018]

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

Retrospective review of factors leading to dissatisfaction with subthalamic nucleus deep brain stimulation during long-term management. [2021]

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

A randomized trial of deep-brain stimulation for Parkinson's disease. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. [2023]

6. 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]

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

Depression leading to attempted suicide after bilateral subthalamic nucleus stimulation for Parkinson's disease. [2023]

8. 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]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Complications and adverse effects of deep brain stimulation in Parkinson's patients. [2009]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Changes in intracortical inhibition and clinical symptoms after STN-DBS in Parkinson's disease. [2016]

12. Poland pubmed.ncbi.nlm.nih.gov

[Bilateral deep brain stimulation of subthalamic nucleus STN in the surgical treatment of Parkinson's disease]. [2015]

13. England pubmed.ncbi.nlm.nih.gov

Functional segregation of basal ganglia pathways in Parkinson's disease. [2019]