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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new type of deep brain stimulation (DBS) to assist individuals with essential tremor, a condition causing uncontrollable shaking, primarily in the hands. The treatment employs a "closed-loop" system that activates only when necessary, aiming to reduce side effects such as slurred speech and walking difficulties. This approach may suit those who have had essential tremor for over three years, experience significant tremor despite medication, and find it disrupts daily tasks like eating or writing. Participants will compare continuous and closed-loop DBS to determine which is more effective. As an unphased trial, this study provides a unique opportunity to explore innovative treatment options that could significantly enhance daily life.

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.

What prior data suggests that this closed-loop deep brain stimulation is safe for essential tremor?

Research has shown that a new method called closed-loop deep brain stimulation (DBS) could be a promising treatment for essential tremor. This technique detects movements that cause tremors and provides stimulation only when necessary. This targeted approach may help reduce side effects like slurred speech and walking difficulties, which can occur with continuous DBS.

Previous studies suggest that closed-loop DBS might save energy and reduce these side effects. While researchers are still collecting information on its long-term safety, early results are promising. If closed-loop DBS continues to show positive results, it could become a safer and more efficient way to manage essential tremor symptoms. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about closed-loop deep brain stimulation (DBS) for essential tremor because it offers a smarter, more responsive treatment approach compared to traditional methods. Most current treatments for essential tremor, like medication or standard DBS, deliver continuous therapy without adjusting to the brain's real-time needs. In contrast, closed-loop DBS uses Medtronic's Summit RC+S device to record brain signals and adjust the stimulation based on the brain's activity. This personalized approach not only aims to improve tremor control but also to minimize side effects by delivering stimulation only when necessary.

What evidence suggests that closed-loop deep brain stimulation is effective for essential tremor?

Research has shown that deep brain stimulation (DBS) effectively treats movement disorders like essential tremor, with studies indicating that DBS can reduce tremors by up to 59%. In this trial, all participants will undergo unilateral DBS implantation. The trial will compare continuous (open-loop) DBS with a newer type, called closed-loop DBS, which uses brain signals to decide when to activate. This method may help reduce side effects and extend battery life. One study found that closed-loop DBS activated the stimulation about 80% of the time when movements causing tremors occurred, suggesting it could be a promising option for managing essential tremor while avoiding unnecessary stimulation. ^{1 2 4 5 6}

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.

I have a severe health condition that could affect my surgery.

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

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) 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) 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]

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) 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]

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) 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7610625/

Closed‐Loop Deep Brain Stimulation for Essential Tremor ... Results. Using the proposed method, stimulation was switched on for 80.37 ± 7.06% of the time when tremor‐evoking movements were present. In ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02649166

Responsive Deep Brain Stimulator for Essential Tremor The overall objective of this early feasibility study is to provide preliminary data on the safety and efficacy of "closed-loop" deep brain ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0022510X22000521

Deep brain stimulation for the treatment of tremor The earlier Vim DBS cohort reported 32% reduction of tremor, compared to 59% reduction in the more recently treated cZI DBS group. Patient ...

4. science.org science.org/doi/10.1126/scitranslmed.aay7680

Chronic embedded cortico-thalamic closed-loop deep ... Deep brain stimulation (DBS) has been shown to be effective for treating movement disorders, including essential tremor (ET).

5. journals.plos.org journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1009281

Optimal closed-loop deep brain stimulation using multiple ... We construct a closed-loop DBS strategy describing how stimulation should be delivered to individual contacts using the phases and amplitudes of feedback ...

6. withpower.com withpower.com/trial/closed-loop-deep-brain-stimulation-for-essential-tremor-7b2d4

Closed-Loop Deep Brain Stimulation for Essential Tremor This study shows that closed loop deep brain stimulation (NclDBS) using an implanted neurostimulator is feasible and effective for treating tremor and ...