Closed-Loop Deep Brain Stimulation for Essential Tremor

Overseen By Aysegul Gunduz, Ph.D

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Must be taking: Propranolol, Primidone

Disqualifiers: Parkinsonian tremor, Substance abuse, Severe comorbidity, Abnormal MRI, others

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

Compensation: Varies

Number of Visits: 10

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Essential tremor is an incurable, degenerative brain disorder that results in increasingly debilitating tremor, and afflicts an estimated 7 million people in the US. In one study, 25% of essential tremor patients were forced to change jobs or take early retirement because of tremor. Essential tremor is directly linked to progressive functional impairment, social embarrassment, and even depression. The tremor associated with essential tremor is typically slow, involves the hands (and sometimes the head and voice), worsens with intentional movements, and is insidiously progressive over many years. Deep brain stimulation has emerged as a highly effective treatment for intractable, debilitating essential tremor. However, since the intention tremor of essential tremor is typically intermittent, and commonly absent at rest, the currently available continuous deep brain stimulation may be delivering unnecessary current to the brain that increases undesirable side effects such as slurred speech and walking difficulty, and hastens the depletion of device batteries, necessitating more frequent surgical procedures to replace spent pulse generators. The overall objective of this early feasibility study is to provide preliminary data on the safety and efficacy of "closed-loop" deep brain stimulation for intention tremor using novel deep brain stimulation devices capable of continuously sensing brain activity and delivering therapeutic stimulation only when necessary to suppress tremor.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, it mentions that your tremor should not be adequately controlled by medications for at least three months before the implant, suggesting you may need to continue your current treatment until the trial begins.

Is closed-loop deep brain stimulation safe for humans?

Deep brain stimulation (DBS) has been used safely in humans for conditions like essential tremor and Parkinson's disease. Most reported side effects are mild and can be managed by adjusting the device settings. However, some complications like infections and device issues have been noted, which sometimes require additional surgery. ^{1 2 3 4 5}

How is closed-loop deep brain stimulation treatment different from other treatments for essential tremor?

Closed-loop deep brain stimulation (DBS) is unique because it uses sensors to adjust the stimulation based on the patient's specific needs, providing feedback to deliver stimulation only when necessary. This approach can reduce side effects and extend the battery life of the device compared to traditional continuous (open-loop) DBS, which does not adapt to changes in the patient's condition. ^{4 6 7 8 9}

What data supports the effectiveness of the treatment Closed-loop Deep Brain Stimulation for Essential Tremor?

Research shows that closed-loop deep brain stimulation (DBS) can effectively reduce tremors in essential tremor patients by adjusting stimulation based on real-time feedback from sensors, which helps to minimize side effects and improve energy efficiency compared to traditional DBS. Studies have demonstrated that this approach can achieve similar tremor suppression as continuous DBS while using less energy, making it a promising treatment option. ^{4 6 10 11 12}

Who Is on the Research Team?

Aysegul Gunduz, Ph.D

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for adults over 21 with severe essential tremor in the arms that hasn't improved after trying at least two medications, including propranolol or primidone. Participants must have had this condition for at least three years and be able to attend all study follow-ups. Pregnant individuals, those with substance abuse issues, major health problems, previous brain surgeries, Parkinsonian features, recent seizures or psychosis are not eligible.

Inclusion Criteria

You have experienced difficulty with speaking, eating, drinking, personal hygiene, dressing, writing, working, or social activities, as measured by a specific scoring system.

You provide informed consent.

You are available for appropriate follow-up times for the length of the study.

Exclusion Criteria

In addition, patients who are pregnant or plan to become pregnant will be excluded from this study.

I may have symptoms like slow movement, stiffness, or balance problems.

You have a history of alcohol or drug abuse as outlined in the DSM-V.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Procedure

Participants undergo unilateral deep brain stimulation (DBS) implantation for essential tremor

1 week

1 visit (in-person)

Post-Surgery Follow-up

Participants are seen monthly post-surgery for 6 months to monitor the effects of DBS

6 months

6 visits (in-person)

Treatment Adjustment

Closed-loop deep brain stimulation may be offered and settings adjusted based on data assessment

18 months

3 visits (in-person) every 6 months

Long-term Follow-up

Participants are monitored yearly if they continue active stimulation after the initial 24-month study period

Ongoing

Yearly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Closed-loop deep brain stimulation
• Deep brain stimulation

Trial Overview The study tests a new 'closed-loop' deep brain stimulation device designed to treat arm tremors by delivering electrical impulses only when needed. This could reduce side effects compared to traditional continuous stimulation and extend battery life of the device.

How Is the Trial Designed?

Group I: Deep brain stimulation Experimental Treatment 2 Interventions

All participants will undergo unilateral deep brain stimulation (DBS) implantation for essential tremor. Medtronic Summit RC+S devices will be used because these are capable of recording brain signals, as well as delivering DBS. Participants will receive continuous (open-loop) and closed-loop deep brain stimulation interventions, which will be compared for efficacy.

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Medtronic

Industry Sponsor

Trials

627

Recruited

767,000+

Geoff Martha

Medtronic

Chief Executive Officer since 2020

Finance degree from Penn State University

Dr. Richard Kuntz

Medtronic

Chief Medical Officer since 2023

MD, MSc

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

This study shows that closed loop deep brain stimulation (NclDBS) using an implanted neurostimulator is feasible and effective for treating tremor and bradykinesia in Parkinson's disease patients, improving symptoms while using significantly less electrical energy compared to traditional open loop stimulation (olDBS).

NclDBS was well-tolerated by all 13 participants, with significant improvements in bradykinesia and tremor control, indicating that this method could provide a more efficient and patient-friendly approach to managing Parkinson's symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual threshold neural closed loop deep brain stimulation in Parkinson disease patients. Velisar, A., Syrkin-Nikolau, J., Blumenfeld, Z., et al.[2019]

Deep brain stimulation (DBS) is a highly effective and safe surgical treatment for advanced Parkinson's disease, essential tremor, and dystonia, significantly improving motor symptoms and quality of life in carefully selected patients.

DBS works by modulating cortical activity and reducing the need for medication, making it a reversible option that promotes better movement efficiency and understanding of the underlying neurocircuitry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Movement disorders and neuromodulation. Shipton, EA.[2022]

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]

Deep brain stimulation (DBS) has been shown to significantly improve symptoms in patients with essential tremor, with 430 patients studied, indicating its potential effectiveness for this movement disorder.

Most adverse events related to DBS were mild and manageable by adjusting stimulation settings, suggesting that DBS is a relatively safe treatment option for essential tremor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for essential tremor: a systematic review. Flora, ED., Perera, CL., Cameron, AL., et al.[2022]

Deep-brain stimulation (DBS) targeting the ventral intermediate (VIM) nucleus and posterior subthalamic area (PSA) is shown to be a safe and effective treatment for patients with medically refractory essential tremor (ET), improving tremor reduction and daily activities.

While both DBS targets are effective, the literature on PSA is limited, particularly regarding bilateral stimulation and long-term outcomes, indicating a need for further research to compare the safety and efficacy of these targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current clinical application of deep-brain stimulation for essential tremor. Chopra, A., Klassen, BT., Stead, M.[2022]

Deep brain stimulation (DBS) is a safe and effective surgical treatment for advanced Parkinson's disease, with a low incidence of serious complications, as shown in a study of 130 patients over several years.

In this study, 62% of patients experienced no complications, and the most common issues were minor, such as aborted procedures (5.14%) and seizures (4.7%), indicating that DBS has a favorable safety profile compared to other surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications in subthalamic nucleus stimulation surgery for treatment of Parkinson's disease. Review of 272 procedures. Seijo, FJ., Alvarez-Vega, MA., Gutierrez, JC., et al.[2019]

Deep brain stimulation (DBS) shows long-term efficacy in controlling essential tremor, with significant reductions in Tremor Rating Scale scores from a mean of 7 to 3 after treatment, based on a follow-up of 41 months for 26 patients.

Quality of life improved significantly with DBS, as indicated by a decrease in ADL Taxonomy scores from a mean of 26 to 12, and the effectiveness of DBS remained consistent regardless of the duration of follow-up, indicating sustained benefits over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of deep brain stimulation for essential tremor with subjective and objective quantification via mailed-in questionnaires. de Oliveira, TH., Ginsberg, MR., Cooper, S., et al.[2015]

Citations

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

Chronic electrocorticography for sensing movement intention and closed-loop deep brain stimulation with wearable sensors in an essential tremor patient. [2019]

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

Chronic embedded cortico-thalamic closed-loop deep brain stimulation for the treatment of essential tremor. [2021]

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

Dual threshold neural closed loop deep brain stimulation in Parkinson disease patients. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Adaptive Brain Stimulation for Movement Disorders. [2021]

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

Movement disorders and neuromodulation. [2022]

6. United States 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. [2023]

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

Deep brain stimulation for essential tremor: a systematic review. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Current clinical application of deep-brain stimulation for essential tremor. [2022]

9. Austria pubmed.ncbi.nlm.nih.gov

Complications in subthalamic nucleus stimulation surgery for treatment of Parkinson's disease. Review of 272 procedures. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Long-term effects of deep brain stimulation for essential tremor with subjective and objective quantification via mailed-in questionnaires. [2015]

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

Long-term detection of Parkinsonian tremor activity from subthalamic nucleus local field potentials. [2020]

12. England pubmed.ncbi.nlm.nih.gov

Rehabilitation of the Parkinson's tremor by using robust adaptive sliding mode controller: a simulation study. [2022]