Neurostimulation for Parkinson's Disease

Recruiting at 4 trial locations

Overseen By Andrew Schnaubelt, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Nebraska

Disqualifiers: Hypertension, Heart disease, Seizures, others

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

Compensation: Varies

Number of Visits: 4

20 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, it mentions that your motor symptoms should be severe enough despite optimized medical therapy, suggesting you may continue your current Parkinson's medications.

What data supports the effectiveness of the treatment Sub-clinical stimulation for Parkinson's Disease?

Research shows that electrical stimulation of the subthalamic nucleus can improve motor symptoms and quality of life in patients with advanced Parkinson's disease, suggesting it might be beneficial even at earlier stages of the disease. ^{1 2 3 4 5}

Is neurostimulation for Parkinson's disease generally safe for humans?

Neurostimulation, specifically deep brain stimulation, has been used for Parkinson's disease, but it can have complications. About 25% of patients may experience issues, and 4-6% could have lasting neurological problems. It's important to understand these risks when considering this treatment. ^{2 6 7 8 9}

How does sub-clinical stimulation differ from other treatments for Parkinson's disease?

Sub-clinical stimulation, a form of neurostimulation, is unique because it involves high-frequency electrical stimulation of the subthalamic nucleus, which can improve motor symptoms and emotional processing in Parkinson's disease by enhancing dopamine release and altering neuronal activity. This approach is different from traditional drug treatments like levodopa, which primarily focus on replacing dopamine. ^{1 3 10 11 12}

What is the purpose of this trial?

Parkinson's disease (PD) is a neurodegenerative disorder that leads to both motor and non-motor symptoms. Therapies have been developed that effectively target the motor symptoms. Non-motor symptoms are far more disabling for patients, precede the onset of motor symptoms by a decade, are more insidious in onset, have been less apparent to clinicians, and are less effectively treated. Sleep dysfunction is oftentimes the most burdensome of the non-motor symptoms. There are limited options for treating sleep dysfunction in PD, and the mainstay of therapy is the use of sedative-hypnotic drugs without addressing the underlying mechanisms. Patients with PD who demonstrate significant motor fluctuations and dyskinesia are considered for subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. Several studies have reported that STN-DBS also provides benefit for sleep dysregulation. Additionally, local field potentials recorded from STN DBS electrodes implanted for the treatment of PD, have led to the identification of unique patterns in STN oscillatory activity that correlate with distinct sleep cycles, offering insight into sleep dysregulation. This proposal will leverage novel investigational DBS battery technology (RC+S Summit System; Medtronic) that allows the exploration of sleep biomarkers and prototyping of closed-loop stimulation algorithms, to test the hypothesis that STN contributes to the regulation and disruption of human sleep behavior and can be manipulated for therapeutic advantage. Specifically, in PD patients undergoing STN-DBS, the investigators will determine whether STN oscillations correlate with sleep stage transitions, then construct and evaluate sensing and adaptive stimulation paradigms that allow ongoing sleep-stage identification, and induce through adaptive stimulation an increase in duration of sleep stages associated with restorative sleep.

Research Team

Casey Halpern, MD

Principal Investigator

Stanford University

Clete Kushida, MD, PhD

Principal Investigator

Stanford University

John Thompson, PhD

Principal Investigator

University of Colorado, Denver

Aviva Abosch, MD, PhD

Principal Investigator

University of Nebraska

Eligibility Criteria

This trial is for adults aged 21-80 with Parkinson's Disease (PD) who have severe motor symptoms not adequately managed by medication, and are candidates for deep brain stimulation surgery. They must have had PD motor symptoms for at least 4 years, no significant cognitive deficits or depression, and no history of certain medical conditions like seizures or heart disease.

Inclusion Criteria

My Parkinson's symptoms improve by at least 30% with medication, or I have significant, treatment-resistant tremor.

Ability to provide informed consent for this study

My Parkinson's symptoms haven't improved with oral medications.

Exclusion Criteria

I have had brain surgery before.

Pre-existing implanted stimulation system (e.g., cochlear implant, cardiac pacemaker, defibrillator, neuro-stimulator for indication other than Parkinson's disease) or ferromagnetic metallic implant

I do not have uncontrolled blood pressure, bleeding disorders, seizures, heart disease, or issues with anesthesia.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Recovery

Participants undergo standard-of-care STN DBS lead implantation surgery for the treatment of PD

3 weeks

1 visit (in-person)

In-patient Sleep Lab

Participants return for 3 nights of STN LFP recordings with concurrent PSG, EMG, EOG, actigraphy, and video-EEG to establish a physiological sleep baseline and test sub-clinical stimulation

1 week

3 visits (in-patient)

Adaptive Stimulation Implementation

Implementation of adaptive stimulation algorithm developed in Aim 1 during nighttime sleep over 3 weeks of in-home sleep

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after adaptive stimulation

4 weeks

Treatment Details

Interventions

• Sub-clinical stimulation

Trial Overview The study tests if subthalamic nucleus oscillations can be linked to sleep stages in PD patients and whether adaptive neurostimulation can increase restorative sleep. It uses advanced DBS technology to identify sleep biomarkers and create stimulation patterns that adapt to ongoing sleep-stage changes.

Participant Groups

Group I: PD with DBS Experimental Treatment 1 Intervention

Patients with Parkinson's Disease who opt for DBS surgery and consent to participate in the sleep study.

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Findings from Research

Deep brain stimulation is an effective treatment for movement disorders, involving an implanted electrode and pulse generator, but its mechanisms of action are not fully understood and were developed without extensive preclinical safety studies.

Complication rates for deep brain stimulation can exceed 25%, with 4-6% of patients experiencing permanent neurological issues, highlighting the need for better understanding of adverse events and safer stimulation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety considerations for deep brain stimulation: review and analysis. Grill, WM.[2007]

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]

Subthalamic nucleus deep brain stimulation (STN DBS) is an effective treatment for both younger (<65 years) and older (≥65 years) patients with Parkinson's disease, showing significant improvements in motor function and medication dosage after 6 months.

While STN DBS is generally safe, older patients experienced a higher rate of complications (11.8%) compared to younger patients (2.6%), suggesting that careful consideration is needed when selecting older patients for this procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral subthalamic deep brain stimulation is an effective and safe treatment option for the older patients with Parkinson's disease. Kim, M., Cho, KR., Park, JH., 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]

References

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

Neurostimulation for Parkinson's disease with early motor complications. [2022]

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

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

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

Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical and cerebral activity changes induced by subthalamic nucleus stimulation in advanced Parkinson's disease: a prospective case-control study. [2016]

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

Subthalamic neurostimulation for Parkinson's disease with early fluctuations: balancing the risks and benefits. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety considerations for deep brain stimulation: review and analysis. [2007]

7. 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]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Bilateral subthalamic deep brain stimulation is an effective and safe treatment option for the older patients with Parkinson's disease. [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. France pubmed.ncbi.nlm.nih.gov

Dopamine efflux in the rat striatum evoked by electrical stimulation of the subthalamic nucleus: potential mechanism of action in Parkinson's disease. [2023]

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

Deep brain stimulation of the subthalamic nucleus enhances emotional processing in Parkinson disease. [2019]

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

Effect of high-frequency stimulation of the subthalamic nucleus on the neuronal activities of the substantia nigra pars reticulata and ventrolateral nucleus of the thalamus in the rat. [2019]