DBS System for Essential Tremor

Overseen By Karim Oweiss, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Must be taking: Propranolol, Primidone

Must not be taking: Anticoagulants

Disqualifiers: Parkinson's, Substance abuse, Severe comorbidities, others

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

Compensation: Varies

Number of Visits: 1

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new device for individuals with essential tremor, a condition that causes shaking during movement. Researchers aim to determine if this implanted device, called ipsilateral thalamic (VIM+VO) DBS, can control tremors more effectively than current treatments. The trial includes two groups: one for individuals whose tremors remain uncontrolled despite current therapy, and another for those who have not received any similar treatment before. Suitable candidates for this trial have experienced essential tremor for at least three years and find their daily life seriously affected despite existing therapy. As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for essential tremor.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that your tremor should be refractory (not responding) to at least two medications, including propranolol or primidone, before participating.

What prior data suggests that this DBS system is safe for essential tremor?

Research shows that deep brain stimulation (DBS) for essential tremor is generally well-tolerated. Past studies found that using DBS on both sides of the brain is safer than other surgical options. When side effects occur, they often relate to the procedure or the device itself, with about 24% of certain DBS types reporting issues. However, these side effects are usually manageable.

The Medtronic Summit RC+S system, a device used for this treatment, is approved for conditions like essential tremor, indicating it is considered safe. While some side effects can occur, they are usually mild and manageable by healthcare providers.

Standard DBS for essential tremor has been well-studied and has shown significant improvements in controlling tremors with a good safety record. Side effects, such as temporary tingling or balance issues, might occur but are often minor.

Overall, DBS systems for essential tremor have a strong safety history and are considered a good option for those who do not respond to medication. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the DBS System for Essential Tremor because it offers a fresh approach to treating this condition. Unlike standard deep brain stimulation (DBS) treatments that typically focus on just one area of the brain, this system targets both the VIM and VO regions of the thalamus with dual leads. This dual targeting could potentially enhance effectiveness and provide relief for patients who haven't responded well to traditional DBS. Additionally, the use of the Medtronic Summit Rechargeable system means the device could maintain its effectiveness for longer periods, reducing the need for frequent battery replacements and improving patient convenience.

What evidence suggests that this device is effective for essential tremor?

Research shows that deep brain stimulation (DBS) in the ventral intermediate nucleus (VIM) can effectively reduce essential tremors. In this trial, participants in the "Refractory Participants" arm will receive optimized VIM DBS therapy. Studies have found that using two leads for DBS in this area significantly lessens tremor severity, as seen in improved tremor rating scores. Meanwhile, the "Treatment Naive" arm will involve long-term stimulation of the thalamus via dual leads. Stimulating the nearby ventralis oralis (VO) has shown initial improvement in controlling tremors, especially in the first three months, although this improvement tends to level off over time. The Medtronic Summit Rechargeable (RC)+S system, used in this trial, allows for personalized adjustments to manage tremors effectively. Standard DBS for essential tremor has proven effective in the long term, with studies showing a 53% to 63% reduction in tremors after one year. ^{2 3 6 7 8}

Who Is on the Research Team?

Karim Oweiss, PhD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for adults over 21 with severe essential tremor that hasn't improved after trying at least two medications and ongoing traditional VIM DBS therapy. Participants must have a specific level of disability due to the tremor, be able to follow up throughout the study, and not have other central nervous system diseases or significant medical conditions.

Inclusion Criteria

My tremor hasn't improved after trying two medications, including propranolol or primidone.

Patient is available for appropriate follow-up times for the length of the study

Patient gives an informed consent

Exclusion Criteria

I might have Parkinson's disease or show symptoms like slow movement, stiffness, or balance problems.

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

You have a serious untreated or unstable mood disorder, like depression.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intraoperative Experiments

Intraoperative experiments to test the dual thalamic DBS lead systems

1 day

1 visit (in-person)

Chronic Testing

Chronic testing of implanted dual thalamic DBS lead systems for tremor control

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ipsilateral thalamic (VIM+VO) DBS
• ipsilateral VO
• Medtronic Summit Rechargable (RC)+S
• standard ET DBS

Trial Overview The study tests new dual lead thalamic DBS systems for controlling severe essential tremors in patients where current treatments aren't enough. It's an early-stage trial to see if this approach works well enough to plan larger trials aimed at FDA approval for these advanced DBS systems.

How Is the Trial Designed?

Group I: Refractory Participants Active Control 2 Interventions

Patients with recurrent, debilitating intention tremor despite ongoing, optimized VIM DBS therapy

Group II: Treatment Naive Active Control 3 Interventions

Participants receiving Long-term stimulation of the thalamus via dual leads for Essential Tremor

ipsilateral thalamic (VIM+VO) DBS is already approved in United States, European Union for the following indications:

Approved in United States as Medtronic DBS Therapy for Tremor for:

• Essential tremor
• Parkinsonian tremor

Approved in European Union as Medtronic DBS Therapy for Tremor for:

• Essential tremor
• Parkinsonian tremor

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

In a study of 10 patients with essential tremor who received constant current deep brain stimulation for an average of 49.7 months, there was a significant improvement in tremor severity, with scores on the Fahn-Tolosa-Marin scale decreasing from 50.7 to 17.4 (a 65.6% improvement).

The quality of life for these patients also improved significantly, as indicated by a reduction in the Quality of Life in Essential Tremor score from 56.2 to 16.8 (a 70.1% improvement), demonstrating the therapy's effectiveness and safety over the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy of Constant Current Deep Brain Stimulation in Essential Tremor. Rezaei Haddad, A., Samuel, M., Hulse, N., et al.[2022]

Deep brain stimulation (DBS) of the thalamic ventralis intermedius nucleus (VIM) is an effective treatment for essential tremor in patients who do not respond to medication, particularly improving hand tremors that affect daily activities.

DBS has been shown to provide better functional outcomes and fewer adverse effects compared to lesional thalamotomy, highlighting its safety and efficacy in managing essential tremor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Deep brain stimulation for essential tremor. Consensus recommendations of the German Deep Brain Stimulation Association]. Sixel-Döring, F., Benecke, R., Fogel, W., et al.[2021]

Unilateral Vim thalamotomy and Vim deep brain stimulation (DBS) significantly improved tremor severity and motor function on the side opposite to the surgery in essential tremor patients, as shown by improvements in the Clinical Rating Scale for Tremor (CRST) scores after 3 and 6 months.

Neither intervention showed significant improvements in tremor on the side of the surgery, indicating that while both treatments are effective for contralateral tremor, they do not benefit the ipsilateral side.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lateralized effects of unilateral thalamotomy and thalamic stimulation in patients with essential tremor. Kim, MJ., Jeon, SR., Kim, SR., et al.[2021]

A patient with severe essential tremor experienced significant tremor control after receiving thalamic stimulation in the same area where he had a thalamotomy 30 years earlier, which had initially reduced his tremor for only one year.

The thalamic stimulation provided nearly complete tremor control and sustained benefits over an 18-month follow-up, indicating that this treatment can be effective for patients with recurrent tremor after previous surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipsilateral thalamic stimulation after thalamotomy for essential tremor. A case report. Racette, BA., Rich, KM., Randle, J., et al.[2017]

Deep brain stimulation (DBS) of the ventral intermediate (Vim) thalamic nucleus is an effective treatment for tremor disorders, particularly essential tremor and tremor-dominant Parkinson's disease.

There are technical variations in the surgical techniques used for Vim DBS, particularly in preoperative imaging and electrode trajectory planning, which can influence the procedure's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Surgical Technique of Ventral Intermediate Thalamic Deep Brain Stimulation]. Morishita, T., Tanaka, H., Inoue, T.[2021]

Unilateral deep brain stimulation (DBS) of the VIM nucleus in the thalamus shows long-term efficacy in reducing essential tremor symptoms, with significant improvements noted in tremor scores at an average follow-up of 40.2 months after surgery.

While the treatment is effective for some patients, it is associated with device-related complications and a risk of loss of efficacy over time, necessitating additional surgical interventions in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of unilateral deep brain stimulation of the thalamus in essential tremor. Koller, WC., Lyons, KE., Wilkinson, SB., et al.[2022]

In a study of 19 patients with tremor-dominant Parkinson's disease, combined deep brain stimulation (DBS) targeting both the subthalamic nucleus (STN) and the ventral intermediate thalamic nucleus (VIM) resulted in significant improvements, with a 38.2% reduction in Unified Parkinson Disease Rating Scale (UPDRS) scores and a 59.0% decrease in tremor scores after an average follow-up of 33.8 months.

The procedure demonstrated a low complication rate of 5.3%, with most patients able to reduce their medication burden, suggesting that this combined approach is both safe and effective for managing symptoms of tremor-dominant Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination targeting of subthalamic nucleus and ventral intermediate thalamic nucleus with a single trajectory in deep brain stimulation for tremor-dominant Parkinson's disease. Fayed, I., Cobourn, KD., Pivazyan, G., et al.[2021]

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is an effective surgical treatment for essential tremors (ETs), particularly for distal appendicular tremors.

The efficacy of DBS varies based on the type of tremor, being less effective for non-distal tremors, highlighting the need for tailored approaches in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Staged Deep Brain Stimulation of Ventral Intermediate Nucleus of the Thalamus for Suppression of Essential Tremors. Tanaka, R., Ansari, A., Kajita, Y., et al.[2020]

In a study involving five patients with essential tremor, deep brain stimulation (DBS) significantly reduced both postural and kinetic tremor scores from preoperative averages of 1.9 and 2.6 to 0.1 and 0.6 one year post-surgery, indicating effective symptom relief.

There was no significant difference in tremor reduction among the different stimulation sites (Vim, PSA, and Vim + PSA), suggesting that individualized electrode placement based on patient response may be an effective approach for treating essential tremor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous thalamic and posterior subthalamic electrode insertion with single deep brain stimulation electrode for essential tremor. Chang, WS., Chung, JC., Kim, JP., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04212780

Dual Lead Thalamic Deep Brain Recording (DBR)-DBS ... Ventralis intermedius nucleus of the thalamus (VIM) Deep Brain Stimulation (DBS) has emerged as a highly effective treatment for essential tremor, ...

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

Deep brain stimulation for the treatment of tremor This dual lead thalamic DBS technique resulted in a reduction of the mean Tolosa-Fahn-Marin Tremor Rating Scale (TRS) scores from 57.0 at ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7761254/

Deep-Brain Stimulation for Essential Tremor and Other Tremor ... This paper reviews the current literature on DBS for tremor, starting with a detailed discussion of current tremor targets.

4. withpower.com withpower.com/trial/phase-essential-tremor-11-2019-7a5b5

DBS System for Essential Tremor Research shows that deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is effective in reducing essential tremors, ...

5. iopscience.iop.org iopscience.iop.org/article/10.1088/1741-2552/ad4742

Probabilistic stimulation mapping from intra-operative ... This study supports the potential of probabilistic analysis of intra-operative stimulation test data to reveal DBS's action mechanisms and to assist surgical ...

6. ufhealth.org ufhealth.org/clinical-trials/dbs-severe-et-closed-loop

DBS Severe ET Closed Loop This study will inform protocols for optimal use of implanted next-gen DBS systems for primarily tremor control in refractory essential tremor.

7. tremorjournal.org tremorjournal.org/articles/10.5334/tohm.918

Appreciating the Potential Impacts of a Second DBS Lead ... In staged bilateral Vim DBS, second lead implantation may possibly alter ipsilateral tremor control. While ipsilateral improvement is common, rarely, it can ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4975099/

Deep brain stimulation for the treatment of uncommon tremor ... Deep brain stimulation (DBS) has become a standard therapy for the treatment of select cases of medication refractory essential tremor and Parkinson's disease.