Deep Brain Stimulation for Essential Tremor

Overseen By Matthew Johnson, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Disqualifiers: Musculoskeletal disorders, Neurological disorder, Pregnancy, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

25 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

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

Research shows that deep brain stimulation (DBS) targeting the ventral intermediate nucleus (VIM) of the thalamus is effective in controlling symptoms of essential tremor, with studies reporting positive long-term outcomes for patients. ^{1 2 3 4 5}

Is deep brain stimulation targeting the ventralis intermedius nucleus safe for humans?

Deep brain stimulation (DBS) of the ventralis intermedius nucleus (VIM) is generally considered safe for treating essential tremor, though some patients may experience adverse effects over time, especially if high voltage is needed. It may be riskier for elderly patients or those with certain brain conditions. ^{1 6 7 8 9}

How is the Vim-DBS treatment for essential tremor different from other treatments?

Vim-DBS is unique because it involves deep brain stimulation targeting a specific part of the brain called the ventralis intermedius nucleus, which can effectively control tremors when other medications fail. Unlike some treatments, it can be done while the patient is asleep, and it uses either direct or indirect targeting methods to precisely reach the brain area responsible for tremors. ^{1 2 3 6 10}

What is the purpose of this trial?

Deep brain stimulation (DBS) targeting the Vim thalamus (ventralis intermedius nucleus) is an FDA-approved neuromodulation therapy for treating postural and action tremor in individuals with essential tremor (ET). The success of this treatment, however, is highly dependent on the ability of clinicians to identify therapeutic stimulation settings through a laborious programming process. There is a strong and growing clinical need for new approaches to provide clinicians with more efficient guidance on how to titrate stimulation settings. This study will leverage subject-specific computational models that can predict neural activation of axonal pathways adjacent to the active electrode(s) and implicated in the therapeutic mechanisms of Vim-DBS to in turn guide clinicians with which stimulation settings are likely to be the most therapeutic on tremor.

Eligibility Criteria

This trial is for individuals with Essential Tremor (ET) who haven't responded well to medications and have a Vim-Deep Brain Stimulation (DBS) implant. Participants must have had a specific type of MRI scan before surgery and a CT scan after. It's not for those with limb movement disorders, other major neurological conditions, previous brain surgeries besides VIM-DBS, or pregnant women.

Inclusion Criteria

I have been diagnosed with Essential Thrombocythemia (ET).

My tremor does not improve with medication.

You have had a VIM-DBS implant on one or both sides of your brain.

Exclusion Criteria

I have had brain surgery before, but not VIM-DBS surgery.

Pregnancy

I have a condition that affects how my arms or legs move.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo deep brain stimulation (DBS) targeting the Vim thalamus with optimization algorithms to identify therapeutic stimulation settings

24 months

Routine clinical follow-up sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment using TETRAS and QUEST questionnaires

24 months

Treatment Details

Interventions

• Vim-Deep Brain Stimulation

Trial Overview The study tests new algorithms to program DBS systems more efficiently in patients with ET. By using computational models that predict neural activation near the implanted electrode, it aims to help clinicians quickly find the best settings to control tremors.

Participant Groups

Group I: Deep Brain Stimulation Experimental Treatment 1 Intervention

Subjects in this study will have been implanted with a DBS lead in the VIM as part of their routine clinical care and have an existing set of brain MRI's.

Vim-Deep Brain Stimulation is already approved in United States, European Union for the following indications:

Approved in United States as Vim-DBS for:

• Essential tremor
• Tremor associated with Parkinson's disease

Approved in European Union as Vim-DBS for:

• Essential tremor
• Tremor associated with Parkinson's disease

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

In a study of 230 patients undergoing deep brain stimulation (DBS) for essential tremor, those who had direct targeting of the ventral intermediate nucleus (VIM) using MRI showed similar clinical outcomes compared to those with indirect targeting.

While direct targeting required lower stimulation amplitudes and improved quality of life scores for hobbies, it was associated with a higher incidence of symptomatic hemorrhages, although all patients recovered without intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct targeting of the ventral intermediate nucleus of the thalamus in deep brain stimulation for essential tremor: a prospective study with comparison to a historical cohort. Wakim, AA., Sioda, NA., Zhou, JJ., et al.[2023]

Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus (VIM) significantly improves tremor and handwriting in patients with essential tremor, with an average tremor score reduction from 3.27 to 0.64 and handwriting score from 2.94 to 0.89 over an average follow-up of 56.9 months.

The treatment is considered safe, with an 80.4% improvement in tremor and 69.7% in handwriting, although some patients may experience tolerance requiring adjustments in stimulation parameters, and the overall hardware-related complication rate was 23.5%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term results of thalamic deep brain stimulation for essential tremor. Zhang, K., Bhatia, S., Oh, MY., et al.[2022]

In a study of 12 patients with essential tremor, asleep deep brain stimulation (DBS) of the ventralis intermedius (Vim) nucleus showed significant clinical improvements, with tremor scores decreasing by an average of 71.2% and daily living activities improving by 74.9% after 6 months.

The procedure was found to be safe, with mild and transient surgical complications, and the effectiveness of asleep DBS was comparable to traditional awake DBS methods, suggesting it could be a viable alternative for treating essential tremor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asleep Deep Brain Stimulation of the Nucleus Ventralis Intermedius for Essential Tremor Using Indirect Targeting and Interventional Magnetic Resonance Imaging: Single-Institution Case Series. Gravbrot, N., Burket, A., Saranathan, M., et al.[2023]

In a study of 47 patients with Essential Tremor, both VIM and cZI deep brain stimulation (DBS) showed significant improvement in tremor scores from 6 months to 4 years post-surgery, indicating both methods are effective for tremor control.

However, VIM-DBS demonstrated superior long-term outcomes compared to cZI stimulation, particularly noticeable at the 3 and 4-year marks, suggesting that VIM remains the preferred target for sustained tremor relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ventral Intermediate Nucleus Versus Zona Incerta Region Deep Brain Stimulation in Essential Tremor. Eisinger, RS., Wong, J., Almeida, L., et al.[2022]

Deep brain stimulation (DBS) of the thalamic ventral intermediate nucleus (VIM) provides long-term tremor relief for patients with Parkinson's disease (PD) and essential tremor (ET), with sustained improvements of 63% and 48% respectively beyond 10 years after surgery.

While patients with dystonia showed initial improvement in tremor (41% at 1 year), this benefit was not maintained over time, indicating that DBS is less effective for dystonic tremor compared to PD and ET.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thalamic deep brain stimulation for tremor in Parkinson disease, essential tremor, and dystonia. Cury, RG., Fraix, V., Castrioto, A., et al.[2017]

Deep brain stimulation (DBS) of the nucleus ventralis intermedius (VIM) is an effective treatment for essential tremor, but some patients may experience deterioration in tremor control over time, necessitating higher stimulation voltages that can cause adverse effects.

In a study of 3 patients, adding a second thalamic lead and using a dual-channel pulse generator allowed for more targeted stimulation, improving tremor control while reducing side effects, suggesting this method could serve as a reversible rescue therapy for patients needing high-intensity stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Confined stimulation using dual thalamic deep brain stimulation leads rescues refractory essential tremor: report of three cases. Yu, H., Hedera, P., Fang, J., et al.[2009]

In a 5-year follow-up study of 38 patients with essential tremor (ET) and Parkinson's disease (PD), thalamic deep brain stimulation (DBS) showed significant long-term efficacy, with patients experiencing up to 100% improvement in tremors depending on the type of stimulation (unilateral or bilateral).

While DBS is generally safe, common adverse effects included paresthesia and pain for unilateral implants, and dysarthria and balance difficulties for bilateral implants, indicating that careful consideration is needed when opting for bilateral stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term evaluation of deep brain stimulation of the thalamus. Pahwa, R., Lyons, KE., Wilkinson, SB., et al.[2022]

Deep brain stimulation (DBS) of the ventralis oralis anterior nucleus (Voa) was successfully used in an 83-year-old patient with medically intractable essential tremor, leading to significant improvement in her dominant hand tremor after 2 years.

Following the initial DBS, Gamma Knife radiosurgery (GKS) targeting the Voa was performed for the nondominant hand tremor, resulting in successful tremor reduction without complications, suggesting that Voa GKS is a safe and effective option for elderly patients with ischemic brain lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ventralis oralis anterior (Voa) deep brain stimulation plus Gamma Knife thalamotomy in an elderly patient with essential tremor: A case report. Oh, BH., Park, YS.[2023]

Colored fractional anisotropy (FA) mapping can effectively identify the prelemniscal radiations (Raprl), which serve as reliable landmarks for locating the borders of the Vim nucleus in patients undergoing gamma knife thalamotomy for tremor management.

In a study of 18 patients, the mean distance between the Raprl and the Vim nucleus was found to be very small (0.77 mm), indicating that FA mapping can enhance the precision of targeting this critical area in the brain for surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prelemniscal Radiations: A New Reliable Landmark of the Thalamic Nucleus Ventralis Intermedius Location. Lefranc, M., Carron, R., Regis, J.[2016]

In a study of 14 patients with essential tremor followed for an average of 7.7 years after VIM-DBS surgery, tremor severity significantly decreased by 73.4% at 6 months but only by 50.1% at the last follow-up, indicating a loss of efficacy over time.

To maintain tremor control, patients required significant increases in stimulation parameters such as voltage and pulse width, suggesting that both disease progression and tolerance to stimulation may contribute to the diminishing effects of VIM-DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Thalamic Deep Brain Stimulation for Essential Tremor: Clinical Outcome and Stimulation Parameters. Rodríguez Cruz, PM., Vargas, A., Fernández-Carballal, C., et al.[2022]

References

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

Direct targeting of the ventral intermediate nucleus of the thalamus in deep brain stimulation for essential tremor: a prospective study with comparison to a historical cohort. [2023]

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

Long-term results of thalamic deep brain stimulation for essential tremor. [2022]

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

Asleep Deep Brain Stimulation of the Nucleus Ventralis Intermedius for Essential Tremor Using Indirect Targeting and Interventional Magnetic Resonance Imaging: Single-Institution Case Series. [2023]

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

Ventral Intermediate Nucleus Versus Zona Incerta Region Deep Brain Stimulation in Essential Tremor. [2022]

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

Thalamic deep brain stimulation for tremor in Parkinson disease, essential tremor, and dystonia. [2017]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Confined stimulation using dual thalamic deep brain stimulation leads rescues refractory essential tremor: report of three cases. [2009]

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

Long-term evaluation of deep brain stimulation of the thalamus. [2022]

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

Ventralis oralis anterior (Voa) deep brain stimulation plus Gamma Knife thalamotomy in an elderly patient with essential tremor: A case report. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Prelemniscal Radiations: A New Reliable Landmark of the Thalamic Nucleus Ventralis Intermedius Location. [2016]

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

Long-term Thalamic Deep Brain Stimulation for Essential Tremor: Clinical Outcome and Stimulation Parameters. [2022]