Personalized Real-Time Deep Brain Stimulation for Parkinson's Disease

Overseen By Jeffrey Negrey, MA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: David Escobar

Must be taking: Levodopa

Disqualifiers: Secondary Parkinsonism, Stroke, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

A prospective cohort of patients scheduled to undergo deep brain stimulation (DBS) implantation surgery for the treatment of Parkinson's disease as per standard of care will be invited to participate in this study. This mechanistic study is aimed at better understanding the role of basal ganglia beta band (11-35 Hz) oscillations and resonance in the manifestation of Parkinson's disease (PD) motor signs using closed-loop electrical neurostimulation, levodopa medication, and computational modeling. The ultimate goal of this study is to inform the development of closed-loop neuromodulation technology that can be programmed and adjusted in real time based on patient-specific neural activity.

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

The trial does not specify if you need to stop your current medications, but it mentions that participants must be able to tolerate delays in taking their daily Parkinson's disease medications.

Is personalized real-time deep brain stimulation for Parkinson's disease generally safe in humans?

Research on electrical stimulation techniques, like peripheral nerve stimulation and spinal cord stimulation, suggests they are generally safe for humans. Long-term studies show only minor tissue reactions, such as fibrous encapsulation, indicating histological safety. Peripheral nerve stimulation has been used safely for decades in various applications. ^{1 2 3 4 5}

How is the treatment Personalized Real-Time Deep Brain Stimulation for Parkinson's Disease different from other treatments?

This treatment is unique because it uses real-time processing to personalize deep brain stimulation, adjusting the electrical impulses based on the patient's specific needs and movements, which can improve motor control more effectively than standard treatments. ^{5 6 7 8 9}

What data supports the effectiveness of the treatment Personalized Real-Time Deep Brain Stimulation for Parkinson's Disease?

Deep brain stimulation (DBS) has been shown to significantly reduce symptoms like off time and dyskinesia (involuntary movements) in Parkinson's disease patients who do not respond well to medication. It is a well-established treatment that influences brain function to relieve symptoms and improve overall functioning. ^{6 10 11 12 13}

Are You a Good Fit for This Trial?

This trial is for people with Parkinson's Disease who are candidates for deep brain stimulation (DBS) surgery. Participants must be able to consent, tolerate delays in their regular medication, and not have conditions like secondary Parkinsonism or stroke.

Inclusion Criteria

I am a candidate for a specific brain surgery to help with my condition.

I have been diagnosed with Parkinson's disease without a known cause.

I can manage if there's a delay in my Parkinson's medication.

Exclusion Criteria

I do not have Parkinson's but have other brain conditions like stroke.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

DBS Surgery and Initial Assessment

Participants undergo DBS implantation surgery and initial assessments are conducted

1 week

In-person visits for surgery and initial assessments

Treatment and Assessment

Participants receive closed-loop DBS and levodopa medication, with assessments conducted multiple times

9 days

Multiple in-person visits for assessments

Follow-up

Participants are monitored for changes in motor function and neural oscillations

3-12 months

1 visit (in-person) for follow-up assessments

What Are the Treatments Tested in This Trial?

Interventions

• Carbidopa/Levodopa
• Neurostimulation

Trial Overview The study tests how well a personalized real-time DBS system works alongside standard medications like Carbidopa/Levodopa. It aims to understand the role of certain brain oscillations in Parkinson's and develop technology that adjusts treatment based on individual neural activity.

How Is the Trial Designed?

Group I: eiDBS suppression Experimental Treatment 1 Intervention

Closed-loop evoked interference DBS that suppresses beta oscillations.

Group II: eiDBS amplification Experimental Treatment 1 Intervention

Closed-loop evoked interference DBS that amplifies beta oscillations.

Group III: Levodopa medication Experimental Treatment 1 Intervention

On-medication, off-stimulation

Group IV: Off DBS Active Control 1 Intervention

Off-stimulation and off-medication

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

Approved in United States as Neurostimulation for:

• Respiratory dysfunction in spinal cord injury patients

Approved in European Union as Neurostimulation for:

• Respiratory failure in spinal cord injury patients
• Neuropathic pain relief

Who Is Running the Clinical Trial?

David Escobar

Lead Sponsor

Trials

1

Recruited

30+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

Deep brain stimulation (DBS) has been shown to significantly reduce off time and dyskinesia in patients with Parkinson's disease, improving their motor function.

New advancements in DBS techniques, such as targeting the pedunculopontine nucleus and using adaptive closed-loop systems, are being explored to enhance treatment for symptoms like freezing and falls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical treatment of Parkinson disease: past, present, and future. Duker, AP., Espay, AJ.[2021]

Deep brain stimulation (DBS) is a safe and reversible treatment option for neurological conditions like essential tremor, Parkinson's disease, and severe obsessive-compulsive disorder, showing significant functional and structural changes in the brain.

DBS induces neuroplasticity through various mechanisms, including increased striatal dopamine release and expression of trophic factors, which may provide neuroprotective effects, particularly in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation: foundations and future trends. Aum, DJ., Tierney, TS.[2022]

Deep brain stimulation (DBS) is an established treatment for neurological disorders, currently used in tens of thousands of patients, and is effective for conditions like involuntary movement disorders, with ongoing research into its use for epilepsy and psychiatric disorders.

DBS works by applying electrical stimulation to specific brain areas, influencing brain function and behavior to alleviate symptoms, rather than replacing damaged tissues or organs, highlighting its unique mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation devices: a brief technical history and review. Coffey, RJ.[2009]

Operative neuromodulation involves using implanted devices to alter nerve signal transmission, showing promise in treating various conditions like chronic pain, spasticity, and respiratory disorders, which can significantly improve patient quality of life.

Emerging technologies in functional neuroprosthetics, such as endoneural prostheses and closed-loop systems, are paving the way for advanced treatments that could restore function in patients with neurological disabilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An introduction to operative neuromodulation and functional neuroprosthetics, the new frontiers of clinical neuroscience and biotechnology. Sakas, DE., Panourias, IG., Simpson, BA., et al.[2019]

Deep brain stimulation (DBS) is an FDA-approved treatment for essential tremor and Parkinson's disease, and it shows promise for other conditions like dystonia and obsessive-compulsive disorder, making it a versatile option for patients with movement disorders.

The exact mechanism of how DBS works is still debated, highlighting the need for further research to fully understand its therapeutic effects and improve its applications in various neurological and psychiatric diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

History, applications, and mechanisms of deep brain stimulation. Miocinovic, S., Somayajula, S., Chitnis, S., et al.[2023]

Peripheral nerve stimulation (PNS) is a less invasive and potentially more cost-effective alternative to spinal cord stimulation (SCS) for treating neurogenic pain, as it targets specific painful areas directly.

A case report demonstrated significant pain relief from median nerve stimulation after SCS failed, highlighting the effectiveness of PNS, which remains underutilized and not widely accepted for reimbursement despite its safety and efficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Refractory neuropathic pain from a median nerve injury: spinal cord or peripheral nerve stimulation? A case report. Dewandre, Q., Dubuisson, A., Kaschten, B., et al.[2022]

Neuromodulation techniques, such as spinal cord stimulation and peripheral nerve field stimulation, show promising efficacy in treating painful conditions like coronary artery disease, peripheral vascular disease, and headaches, despite not being FDA approved for these uses.

The review analyzed a total of 24 studies, including 10 controlled studies for coronary artery disease, 6 for peripheral vascular disease, and 3 for headaches, providing compelling evidence that neuromodulation could benefit patients suffering from these serious conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Some Non-FDA Approved Uses for Neuromodulation: A Review of the Evidence. Lee, S., Abd-Elsayed, A.[2018]

Percutaneously inserted spinal epidural neurostimulation is a safe and simplified alternative to traditional surgical dorsal column stimulation for managing spasticity and intractable pain, as evidenced by a study of 27 tissue specimens from 15 patients.

Long-term histological analysis revealed only dense fibrous encapsulation around the implanted devices, supporting the clinical belief in the safety of this neurostimulation method over a period of up to two years post-implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histological reaction to percutaneous epidural neurostimulation: initial and long-term results. Richardson, RR., Nunez, C., Siqueira, EB.[2004]

Extraneural electrodes are more stable for long-term use compared to intraneural electrodes, which is important for the safety of chronic electrical stimulation applications.

Current guidelines suggest that chronic stimulation should be kept below 30 Hz and effective stimulation time below 50% to minimize risks, but more comprehensive data is needed to establish safe stimulation protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of long-term electrical peripheral nerve stimulation: review of the state of the art. Günter, C., Delbeke, J., Ortiz-Catalan, M.[2021]

Electrical stimulation through injected electrical charge is an effective method for treating various neural disorders, aiding in the restoration of functions in the brain, eyes, ears, spinal cord, nerves, and muscles.

Recent advancements in neural prosthetics and electrical stimulation parameters highlight the potential for implantable devices to improve reliability and efficacy in treating nervous system dysfunctions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implantable neurotechnologies: electrical stimulation and applications. Nag, S., Thakor, NV.[2018]

Epidural electrical stimulation (EES) can be effectively used to improve motor control and locomotion in rats and nonhuman primates, with stable implants that last for several months.

The described protocols allow for precise control of leg movements during locomotion by delivering timed stimulation bursts to specific spinal cord locations, enabling real-time feedback and adaptation for enhanced motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Configuration of electrical spinal cord stimulation through real-time processing of gait kinematics. Capogrosso, M., Wagner, FB., Gandar, J., et al.[2021]

Deep brain stimulation (DBS) and spinal cord stimulation have been effectively used since the 1960s to treat intractable pain and movement disorders, with high-frequency stimulation (HFS) of the subthalamic nucleus (STN) showing significant benefits for Parkinson's symptoms while reducing the need for medication and its side effects.

Recent advancements in DBS technology, including the use of nanotechnologies and new hardware, are expanding treatment possibilities beyond movement disorders to include conditions like epilepsy, psychiatric disorders, and even obesity, paving the way for innovative neuroprosthetic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional neurosurgery for movement disorders: a historical perspective. Benabid, AL., Chabardes, S., Torres, N., et al.[2009]

Neuromodulatory techniques are increasingly used to treat various neurological disorders, including chronic pain, Parkinson's disease, tremor, dystonia, and epilepsy, by targeting different areas of the nervous system.

The chapter reviews both current and past literature on these techniques, highlighting the mechanisms of deep brain stimulation and electrical neuro-network modulation as key components in managing these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DBS and electrical neuro-network modulation to treat neurological disorders. Thompson, A., Morishita, T., Okun, MS.[2012]

Citations

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

Surgical treatment of Parkinson disease: past, present, and future. [2021]

2. Singapore pubmed.ncbi.nlm.nih.gov

Deep brain stimulation: foundations and future trends. [2022]

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

Deep brain stimulation devices: a brief technical history and review. [2009]

4. Austria pubmed.ncbi.nlm.nih.gov

An introduction to operative neuromodulation and functional neuroprosthetics, the new frontiers of clinical neuroscience and biotechnology. [2019]

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

History, applications, and mechanisms of deep brain stimulation. [2023]

6. Italy pubmed.ncbi.nlm.nih.gov

Refractory neuropathic pain from a median nerve injury: spinal cord or peripheral nerve stimulation? A case report. [2022]

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

Some Non-FDA Approved Uses for Neuromodulation: A Review of the Evidence. [2018]

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

Histological reaction to percutaneous epidural neurostimulation: initial and long-term results. [2004]

9. England pubmed.ncbi.nlm.nih.gov

Safety of long-term electrical peripheral nerve stimulation: review of the state of the art. [2021]

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

Implantable neurotechnologies: electrical stimulation and applications. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Configuration of electrical spinal cord stimulation through real-time processing of gait kinematics. [2021]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Functional neurosurgery for movement disorders: a historical perspective. [2009]

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

DBS and electrical neuro-network modulation to treat neurological disorders. [2012]