STN DBS for Parkinson's Disease

Overseen By Kaeli Spight

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Disqualifiers: Neurologic, Psychiatric, Dementia, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

100 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, it mentions that participants must tolerate being off medication or off DBS states, which might imply some adjustments to your current medication regimen.

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

Research shows that STN DBS (deep brain stimulation of the subthalamic nucleus) is effective in improving motor function in Parkinson's disease patients, especially those with advanced symptoms. It is considered a beneficial treatment option for those who experience complications with medication. ^{1 2 3 4 5}

Is STN DBS safe for humans?

STN DBS (Deep Brain Stimulation of the Subthalamic Nucleus) is generally considered safe for treating Parkinson's disease, but some patients may experience side effects like confusion after surgery or psychiatric issues, especially in older individuals. ^{6 7 8 9 10}

How is the STN DBS treatment different from other treatments for Parkinson's disease?

STN DBS (Subthalamic Nucleus Deep Brain Stimulation) is unique because it involves surgically implanting electrodes in the brain to deliver electrical impulses, which helps control motor symptoms in advanced Parkinson's disease. Unlike medications, which are taken orally, this treatment directly targets brain areas responsible for movement control. ^{1 2 5 11 12}

What is the purpose of this trial?

Deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson's disease (PD) can provide substantial motor benefit yet can also produce unwanted mood and cognitive side effects. Although the neural mechanisms underlying benefits and side effects are not well understood, current hypotheses center on the potentially measurable yet currently undefined effects within downstream cortical networks. Limitations of current tools have impeded attempts to assess network connectivity directly and dynamically in humans with implanted DBS; PET lacks the necessary temporal resolution while fMRI is neither optimal nor safe for patients with implanted DBS. In this proposal, to overcome these significant limitations, the investigators apply high-density diffuse optical tomography (HD-DOT) methods to investigate how STN DBS modulates cortical functional networks and behavior in PD patients. HD-DOT uses a collection of functional near-infrared spectroscopy (fNIRS) measurements, free of radiation exposure concerns, and without electrical/metal artifacts or contraindications or safety concerns for DBS. However, common fNIRS systems are critically hampered by typically sparse measurement distributions that lead to poor anatomical specificity, unreliable image quality due to crosstalk with scalp signals, poor spatial resolution, limited field of view, unstable point spread functions, and uneven spatial coverage. HD-DOT solves these problems by using high-density interlaced source and detector imaging arrays that support densely overlapping measurements and anatomical head models that together result in higher spatial resolution, stable point spread functions, and greatly improved isolation of brain signals from scalp signals. The investigators have demonstrated that HD-DOT accurately maps functional connectivity (FC) within and between cortical resting state networks (RSNs) in the outer \~1cm of cortex with comparable temporal and spatial resolution to fMRI. Preliminary data in older controls and STN DBS patients that directly establish validity and feasibility for the proposed studies are provided. A recent comprehensive evaluation of FC in PD (without DBS) using fMRI found reduced within-network FC in visual, somatomotor, auditory, thalamic and cerebellar networks and reduced between-network FC involving predominantly cortical RSNs (somatomotor, sensory and association), some of which correlated with cognitive and motor dysfunction in PD. Notably, striatal RSNs were not abnormal. These data suggest that PD affects the interrelationships of cortical networks in a behaviorally meaningful way, far downstream of focal subcortical neuropathology. STN DBS is known to alter activity in downstream cortical regions that function as nodes within these dynamic cortical networks supporting movement and cognition. Thus, cortical network FC may play a critical role in mediating the impact of STN DBS on motor and non-motor behavior. Location of the stimulating contact may further modulate these downstream effects, due to the complex functional organization of the STN region. Study procedures include motor and cognitive tests, questionnaires, HD-DOT scanning, and MRI scans. The investigators propose to investigate how STN DBS influences downstream cortical network FC using HD-DOT. This information could lead to more efficient clinical optimization of DBS, identify potential cortical targets for less invasive neuromodulation, and lay the groundwork for future more complex experimental manipulations to determine the full range of STN DBS-induced cortical network responses to up-stream focal electrical perturbations, revealing fundamental properties of functional network plasticity.

Research Team

Tamara G Hershey, PhD

Principal Investigator

Washington University Medical School

Eligibility Criteria

This trial is for adults with Parkinson's Disease (PD) who are either planning to have, or have already had, deep brain stimulation surgery in the subthalamic nucleus. It includes those aged 50-75 and a control group without PD matched by age and sex. Exclusions include significant neurological/psychiatric conditions, MRI contraindications, severe visual loss, non-English speakers, and illiteracy.

Inclusion Criteria

I am between 50-75 years old, diagnosed with Parkinson's, and have had DBS surgery.

I am between 20 and 75 years old and do not have a definite diagnosis of Parkinson's disease.

I am between 50 and 75 years old, diagnosed with Parkinson's, and approved for deep brain stimulation surgery.

Exclusion Criteria

Pilot Group: Exclusions include any significant past or current neurologic or psychiatric diagnosis, conditions interfering with testing, and contraindications for MRI

Pre-Surgical DBS Group: Exclusions include contraindications for MRI pre-surgically, inability to tolerate off medication or off DBS states, and conditions interfering with testing

Control Group: Exclusions include any significant past or current neurologic or psychiatric diagnosis, conditions interfering with testing, and contraindications for MRI

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Surgical Assessment

Pre-surgical assessments including MRI/fMRI imaging and cognitive tests

4-6 weeks

Multiple visits for imaging and assessments

Surgical and Post-Surgical Optimization

STN DBS surgery followed by clinical optimization of DBS settings

8-12 weeks

Regular visits for optimization and monitoring

Post-Surgical Testing

Post-surgical testing with HD-DOT and cognitive assessments in ON and OFF DBS states

4-8 weeks

Multiple visits for testing in different DBS states

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• STN DBS

Trial Overview The study tests how STN DBS affects cortical networks related to movement and cognition using HD-DOT scanning technology. This could improve DBS clinical optimization and identify new targets for neuromodulation therapy. Participants will undergo motor/cognitive tests, questionnaires, HD-DOT scans, and MRIs.

Participant Groups

Group I: Post-Surgical Group Experimental Treatment 1 Intervention

STN DBS: Subjects with PD and DBS STN implanted will be scanned and tested with DBS ON and OFF

STN DBS is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as STN DBS for:

• Parkinson's Disease

Approved in United States as STN DBS for:

• Parkinson's Disease

Approved in Canada as STN DBS for:

• Parkinson's Disease

Approved in Japan as STN DBS for:

• Parkinson's Disease

Approved in China as STN DBS for:

• Parkinson's Disease

Approved in Switzerland as STN DBS for:

• Parkinson's Disease

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

In a study of 66 patients with Parkinson's disease treated with subthalamic nucleus deep brain stimulation (STN DBS), there was a significant average reduction of 45% in motor symptoms as measured by the UPDRS III score six months post-implantation.

STN DBS also led to a notable decrease in levodopa consumption, with reductions ranging from 15% to 100%, indicating its potential to enhance treatment efficacy while possibly reducing medication dependency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthalamic deep brain stimulation for the treatment of Parkinson disease. Mandat, T., Tykocki, T., Koziara, H., et al.[2019]

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 52 patients with advanced Parkinson's disease followed for over 3 years, subthalamic nucleus deep brain stimulation (STN DBS) was found to significantly improve motor function, particularly in relation to preoperative levodopa response.

Preoperative activity of daily living (ADL) and levodopa equivalent dose (LED) were identified as strong predictors of improvement in daily functioning after STN DBS, highlighting the importance of these factors in determining treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors related to outcomes of subthalamic deep brain stimulation in Parkinson's disease. Kim, HY., Chang, WS., Kang, DW., et al.[2021]

Patients with Parkinson's disease who underwent deep brain stimulation (STN-DBS) experienced improved motor function and reduced medication dosage in the first year after surgery, while nonmotor symptoms and cognition remained stable.

STN-DBS patients had a delayed onset of morbidity milestones (like falls and dementia) compared to those receiving medical treatment alone, suggesting that while they may live longer with the disease, significant health declines occur in the last 5 years of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morbidity Milestones Demonstrate Long Disability-Free Survival in Parkinson's Disease Patients with Deep Brain Stimulation of the Subthalamic Nucleus. Schnalke, N., Konitsioti, A., Frank, A., et al.[2023]

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 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]

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 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]

Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) was successfully applied to a 54-year-old man with early Parkinson's disease, showing improvements in motor function and quality of life over a two-year follow-up.

The participant experienced no serious adverse events, indicating that STN-DBS may be a safe intervention for early-stage Parkinson's disease, although his medication dosage increased during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for early-stage Parkinson's disease: an illustrative case. Gill, CE., Allen, LA., Konrad, PE., et al.[2022]

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 81 Parkinson's disease patients who underwent deep brain stimulation (DBS) surgery, violating the lateral ventricle during the procedure was significantly associated with postoperative confusion, with a relative risk of 87 (P < .001).

Out of 145 leads implanted, 8 patients experienced confusion and longer hospital stays, and all of these cases had evidence of ventricular wall violation on MRI, suggesting that this complication may contribute to cognitive issues more commonly seen in STN DBS compared to other targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transgressing the ventricular wall during subthalamic deep brain stimulation surgery for Parkinson disease increases the risk of adverse neurological sequelae. Gologorsky, Y., Ben-Haim, S., Moshier, EL., et al.[2011]

References

1. Poland pubmed.ncbi.nlm.nih.gov

Subthalamic deep brain stimulation for the treatment of Parkinson disease. [2019]

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

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

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

Factors related to outcomes of subthalamic deep brain stimulation in Parkinson's disease. [2021]

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

Morbidity Milestones Demonstrate Long Disability-Free Survival in Parkinson's Disease Patients with Deep Brain Stimulation of the Subthalamic Nucleus. [2023]

5. 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]

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. 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]

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. 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]

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

Deep brain stimulation for early-stage Parkinson's disease: an illustrative case. [2022]

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

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

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

Transgressing the ventricular wall during subthalamic deep brain stimulation surgery for Parkinson disease increases the risk of adverse neurological sequelae. [2011]