Cortical Stimulation for Parkinson's Disease

(PC+S_PFC Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Philip Starr

Must be taking: Anti-Parkinsonian

Disqualifiers: Pregnancy, Severe hypertension, Severe diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist people with Parkinson's disease who also face mood issues such as anxiety, depression, or impulsive behavior. The study tests a device called Activa PC+S Prefrontal to determine if it can improve these non-motor symptoms by stimulating specific brain areas. Individuals with Parkinson's disease who experience severe movement problems and mood or behavior issues unresponsive to medication might be suitable for this trial. The researchers aim to discover if this treatment can enhance daily life for those affected by these challenging symptoms. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could improve quality of life for many.

Will I have to stop taking my current medications?

The trial requires that participants have stable doses of anti-Parkinsonian medications for at least 30 days before starting the study. It does not specify if you need to stop other medications, so it's best to discuss this with the study team.

What prior data suggests that cortical stimulation is safe for treating mood and behavioral symptoms in Parkinson's disease?

Research shows that devices like the Activa PC+S, including the Activa PC system, have previously treated Parkinson's disease. These devices have raised some safety concerns. Common issues include infections, movement of the device's wires, and problems with the device itself. However, these risks are typical for this type of treatment.

The FDA has reviewed the Activa PC system, on which the Activa PC+S is based, for safety. This review provides some confidence in its safety for similar uses. However, since the Activa PC+S remains experimental, it might present different risks. Prospective trial participants should discuss these potential risks with the study team. They can provide more detailed information and help clarify what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for the mood disorders and impulsivity associated with Parkinson's Disease, like antidepressants or cognitive behavioral therapy, focus on managing symptoms after they appear. However, the Activa PC+S Prefrontal device is unique because it targets the brain's prefrontal cortex directly, which is believed to play a critical role in these non-motor symptoms. Researchers are excited about this treatment as it may offer a new way to modulate brain activity and potentially improve mood and impulse control more effectively than traditional methods. By directly stimulating the brain, this approach could offer faster relief and tackle the underlying neurophysiology of these symptoms.

What evidence suggests that cortical stimulation is effective for mood and behavioral symptoms in Parkinson's disease?

Research shows that devices like the Activa PC+S Prefrontal, which participants in this trial will receive, might improve mood and behavior in people with Parkinson's disease. Some studies have found that similar devices effectively treat movement problems, and there is hope they can also address non-motor issues like anxiety and depression. Early results indicate that stimulating specific brain areas can alter mood and behavior. Although data on mood and behavior remain limited, targeting brain regions involved in these processes appears promising. Overall, cautious optimism exists that this method could help manage some non-motor symptoms of Parkinson's disease. ^{3 4 6 7 8}

Who Is on the Research Team?

Simon J Little, MBBS, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for Parkinson's disease patients aged 30-75 with severe movement symptoms despite medication, who may benefit from deep brain stimulators. They should have mood or behavioral issues like depression or anxiety and show improvement on medication. Excluded are pregnant women, those with significant cognitive impairment, prior intracranial surgery (other than DBS), major comorbidities, or conditions that could interfere with the study.

Inclusion Criteria

My Parkinson's symptoms improve by at least 30% when I take my medication.

I have Parkinson's with severe tremor not improved by medication or I can't tolerate the medication.

Have one or several mild to moderate mood or impulsive behavior as defined by: depression (BDI>=13), anxiety (BAI >=7), impulsive behavior as indicated by a positive score on the QUIP-A (Questionnaire for Impulsive-Compulsive disorders in Parkinson's Disease) or as determined by clinical interview or informant report

Exclusion Criteria

Any personality or mood symptoms that study personnel believe will interfere with study requirements.

I have had brain surgery, but not for deep brain stimulation.

My immune system is weak.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Treatment

Deep brain surgery (DBS) implantation and initial cortical stimulation setup

4 weeks

In-person visits for surgery and setup

Treatment and Monitoring

Cortical stimulation and monitoring of brain signals and symptoms

24 months

Regular in-person and home visits for monitoring and adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Activa PC+S Prefrontal

Trial Overview The study tests cortical stimulation using Activa PC+S Prefrontal to alleviate mood and behavioral symptoms in Parkinson's patients. Participants will be selected based on specific criteria including their response to medications and severity of symptoms.

How Is the Trial Designed?

Group I: Prefrontal Cortex ECoG Stimulation in Parkinson's Disease Experimental Treatment 4 Interventions

A subset of participants in the recording cohort also received experimental stimulation through the implanted prefrontal ECoG strip. One participant underwent blinded, block-wise prefrontal cortex stimulation during a behavioral task to assess its causal effects on motivation and decision-making. Additionally, two participants received blinded, chronic prefrontal stimulation at home over a 14-day period, in conjunction with their ongoing subcortical motor DBS. These participants completed daily self-reports of mood and anxiety symptoms during the stimulation period. All stimulation protocols were experimental and distinct from routine motor DBS programming. Clinical DBS and medication adjustments were made exclusively as part of routine care and were not affected by the study procedures.

Group II: Chronic Neural Recording with Prefrontal Cortex ECoG in Parkinson's Disease Experimental Treatment 3 Interventions

Participants with Parkinson's disease underwent deep brain stimulation (DBS) lead implantation targeting either the subthalamic nucleus or globus pallidus internus for motor symptom management. A permanent 4-contact subdural electrocorticography (ECoG) strip was also placed over the right prefrontal cortex and connected to a Medtronic Activa PC+S neurostimulator. This setup enabled chronic recording of local field potentials from the prefrontal cortex during daily life and structured experimental tasks. Neural and behavioral data were collected through decision-making tasks and longitudinal self-report of mood and symptoms using a tablet-based tool. Clinical DBS and medication adjustments were performed solely as part of standard care and were not influenced by participation in the study.

Who Is Running the Clinical Trial?

Philip Starr

Lead Sponsor

Trials

1

Recruited

10+

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Simon J. Little, MBBS, PhD

Lead Sponsor

Trials

1

Recruited

10+

Published Research Related to This Trial

A review of 221 unique adverse events related to deep brain stimulation (DBS) devices for Parkinson's disease revealed that the most common complications were infections (16.2%) and lead migrations (8.6%).

Over 40% of the reported adverse events required patients to return to the operating room for device explantation or revision, highlighting the need for further research to improve the safety and reliability of DBS systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing Complications of Deep Brain Stimulation Devices for the Treatment of Parkinsonian Symptoms Without Tremor: A Federal MAUDE Database Analysis. Bennett, J., MacGuire, J., Novakovic, E., 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 of 40 Parkinson's disease patients undergoing subthalamic deep brain stimulation (STN-DBS), 45% reported significant improvement in sleep quality at 6 months, although this improvement was not statistically significant at 12 months.

The most common benefits included better overall sleep quality and maintenance, but some patients experienced new-onset daytime sleepiness, indicating that while STN-DBS can improve sleep, the effects can vary widely among individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in Parkinson's disease sleep symptoms and daytime somnolence after bilateral subthalamic deep brain stimulation in Parkinson's disease. Kharkar, S., Ellenbogen, JR., Samuel, M., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8568318/

Prefrontal Physiomarkers of Anxiety and Depression in ... To understand prefrontal physiological correlates of anxiety and depression in PD, we studied four patients with PD who met standard clinical ...

2. withpower.com withpower.com/trial/phase-parkinson-disease-11-2016-aaf52

Cortical Stimulation for Parkinson's Disease (PC ... Trial Overview The study tests cortical stimulation using Activa PC+S Prefrontal to alleviate mood and behavioral symptoms in Parkinson's patients. Participants ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01984710

Study Details | NCT01984710 | Deep Brain Stimulation for ... The goal of this study is to use the Activa Primary Cell + Sensing (PC+S) device to study Latent Field Potential (LFP) in the brains of people with Treatment ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11103221/

Emerging therapies for neuromodulation in Parkinson's ... Deep brain stimulation (DBS) is an example of an effective neuromodulatory approach, mainly for the treatment of motor symptoms. DBS has evolved ...

5. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2022.813387/full

Proceedings of the Ninth Annual Deep Brain Stimulation ... These results demonstrate that there are meaningful behavioral features that track with acute and chronic brain changes, potentially enabling the future ...

6. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf/P960009S219b.pdf

summary of safety and effectiveness data (ssed) The Activa PC Neurostimulation System includes Activa Parkinson's Control Therapy and Activa Tremor Control Therapy. Bilateral stimulation of ...

7. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf/p960009s007b.pdf

summary of safety and effectiveness data - accessdata.fda.gov Summary of Safety and Effectiveness Data page 9. Activa Parkinson's Control Therapy. Patients participated in the studies for 12 months; there ...

8. medtronic.com medtronic.com/se-sv/healthcare-professionals/products/neurological/deep-brain-stimulation-systems/activa-pc.html

Activa PC - Deep Brain Stimulation Systems Medtronic DBS systems are MR Conditional and safe in the MR environment as long as certain conditions are met. If the conditions are not met, a significant risk ...