Deep Brain Stimulation for Essential Tremor

Overseen By Peter M Grund, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Minnesota

Must not be taking: Tremor-inducing medications

Disqualifiers: Musculoskeletal disorders, Neurological disorder, Dementia, Psychiatric disease, 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

23 Participants Needed

Trial Summary

What is the purpose of this trial?

Deep brain stimulation (DBS) is a surgical procedure for the treatment of Essential Tremor (ET). A novel approach to current DBS approaches is called coordinated reset DBS (CR-DBS) which uses different patterns of stimulation at lower currents and can address the limitations of traditional DBS that uses continuous high amplitude, high frequency stimulation. This study will evaluate the feasibility, safety and short-term efficacy of thalamic CR-DBS in upper extremity ET. The goal of this study is to evaluate the safety and short-term efficacy of thalamic CR- DBS in ET, including the acute (during CR-DBS) and carryover (following DBS cessation) effects, and compare these to those induced by clinically optimized T-DBS. To achieve our goal, a low-risk, two-phase clinical study will be conducted in patients with upper extremity (UE) ET. The first aim is to identify the spatial location and peak frequency of tremor related oscillatory activities in VIM (Phase I). The second aim is to compare the acute effects of thalamic CR-DBS to clinically optimized T-DBS (Phase II).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on medication that could cause tremor.

What data supports the effectiveness of the treatment Coordinated Reset Deep Brain Stimulation (CR-DBS) for essential tremor?

Research shows that thalamic deep brain stimulation (DBS) can significantly reduce tremors in patients with essential tremor, with some studies reporting at least 50% improvement. Although specific data on CR-DBS is not provided, the effectiveness of thalamic DBS in general suggests potential benefits for CR-DBS as well. ^{1 2 3 4 5}

Is deep brain stimulation safe for essential tremor?

Deep brain stimulation (DBS) for essential tremor has been studied for its safety, and while it is generally considered safe, some patients may experience side effects. These can include changes in mood, cognition (thinking and memory), and other adverse events, especially in older patients. ^{1 3 4 6 7}

How is Coordinated Reset Deep Brain Stimulation (CR-DBS) different from other treatments for essential tremor?

Coordinated Reset Deep Brain Stimulation (CR-DBS) is unique because it uses a specific pattern of electrical pulses to disrupt abnormal brain activity, potentially offering a more targeted approach compared to traditional deep brain stimulation, which typically uses continuous stimulation. ^{1 2 3 4 6}

Research Team

Jing Wang, PhD

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for adults over 21 with Essential Tremor (ET) affecting their upper extremities, who will have a Boston Scientific Vercise Rechargeable Genus DBS system implanted and can undergo specific MRI scans. It's not suitable for those with other central nervous system diseases, musculoskeletal or significant neurological disorders, cognitive impairments, psychiatric diseases, tremors caused by medication, prior brain surgery or Parkinsonian features.

Inclusion Criteria

I have been diagnosed with Essential Tremor.

I am scheduled for a CT scan after surgery.

I am 21 years old or older.

Exclusion Criteria

I have had brain surgery before.

Pregnant women

I may have symptoms similar to Parkinson's disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I

Identify the spatial location and peak frequency of tremor related oscillatory activities in VIM

2 months

Phase II

Compare the acute effects of thalamic CR-DBS to clinically optimized T-DBS

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

Treatment Details

Interventions

• Coordinated Reset Deep Brain Stimulation

Trial Overview The study tests a new type of Deep Brain Stimulation called coordinated reset DBS (CR-DBS), which uses varied stimulation patterns at lower currents to potentially improve Essential Tremor symptoms in the arms. The effects during and after treatment are compared to traditional high-frequency DBS.

Participant Groups

Group I: Coordinated Reset DBS Setting (CR-DBS) Experimental Treatment 1 Intervention

Coordinated Reset DBS settings

Group II: Clinically Optimized DBS Setting (T-DBS) Experimental Treatment 1 Intervention

Traditional DBS settings

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

Approved in European Union as Coordinated Reset DBS for:

• Essential Tremor
• Parkinson's Disease

Approved in United States as Coordinated Reset DBS for:

• Essential Tremor
• Parkinson's Disease

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

Thalamic deep brain stimulation (DBS) significantly improves tremor control and daily functioning in individuals with essential tremor, as shown in a study of 52 patients over three years with consistent improvements at various postoperative intervals.

The treatment is generally well-tolerated, although dysarthria (speech difficulties) was more common in patients with bilateral stimulation, indicating a need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thalamic deep brain stimulation for essential tremor: recommendations for long-term outcome analysis. Putzke, JD., Wharen, RE., Obwegeser, AA., et al.[2019]

In a study involving 9 patients with essential tremor, it was found that increasing the interphase gap in symmetric biphasic pulses during deep brain stimulation significantly lowered both the therapeutic threshold and side-effect threshold, indicating a reduced therapeutic window.

The results suggest that using zero interphase gaps in anode-first biphasic pulses provides the largest therapeutic window, which may enhance the effectiveness and safety of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interphase Gaps in Symmetric Biphasic Pulses Reduce the Therapeutic Window in Ventral Intermediate Nucleus of the Thalamus-Deep Brain Stimulation for Essential Tremor. Boogers, A., Peeters, J., Van Bogaert, T., et al.[2023]

In a study of 37 patients with essential tremor, optimal lead placement for thalamic deep brain stimulation (DBS) was found to be 6.3 mm anterior and 12.3 mm lateral to the posterior commissure, significantly improving tremor control.

Leads positioned more than 2 mm away from this optimal location were associated with poorer tremor control, highlighting the importance of precise electrode placement in achieving effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thalamic deep brain stimulation for essential tremor: relation of lead location to outcome. Papavassiliou, E., Rau, G., Heath, S., et al.[2008]

In a study of 37 patients with essential tremor, optimal lead placement for thalamic deep brain stimulation (DBS) was found to be 6.3 mm anterior and 12.3 mm lateral to the posterior commissure, significantly improving tremor control.

Leads positioned more than 2 mm away from this optimal location were associated with poorer tremor control, with only a 9% incidence of true physiological tolerance to the DBS effect, indicating precise lead placement is crucial for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thalamic deep brain stimulation for essential tremor: relation of lead location to outcome. Papavassiliou, E., Rau, G., Heath, S., et al.[2022]

In a study of 13 patients undergoing thalamic deep brain stimulation (DBS) over 3 to 5 years, all initially showed at least a 50% improvement in tremor, indicating the treatment's efficacy for tremor control.

By the last follow-up, some patients with Parkinson's disease experienced significant tremor improvement, leading to a reduction in DBS usage, while others developed tolerance to the stimulation, highlighting the variability in long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of thalamic deep brain stimulation for essential and parkinsonian tremor. Kumar, R., Lozano, AM., Sime, E., et al.[2022]

Unilateral thalamic deep brain stimulation (DBS) significantly reduced tremors in patients with essential tremor (ET) by 83% and in those with Parkinson's disease (PD) by 82%, demonstrating its efficacy in treating severe tremors that are resistant to medication.

The treatment was generally safe, with mild adverse events more common in ET patients, which were often resolved by adjusting the device settings; however, DBS did not improve other motor symptoms in PD patients, indicating it should be used selectively for those with significant tremor-related disability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unilateral thalamic deep brain stimulation for refractory essential tremor and Parkinson's disease tremor. Ondo, W., Jankovic, J., Schwartz, K., et al.[2019]

In a study of 26 patients with essential tremor, thalamic deep brain stimulation (DBS) was found to be safe and effective for managing tremors, regardless of whether patients were younger or older than 70 years.

After following patients for 2 years, the study showed no significant differences in clinical outcomes related to tremor, cognition, or mood between the two age groups, indicating that age does not impact the efficacy of DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral thalamic deep brain stimulation for essential tremor in elderly patients. Klein, J., Büntjen, L., Jacobi, G., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Thalamic deep brain stimulation for essential tremor: recommendations for long-term outcome analysis. [2019]

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

Interphase Gaps in Symmetric Biphasic Pulses Reduce the Therapeutic Window in Ventral Intermediate Nucleus of the Thalamus-Deep Brain Stimulation for Essential Tremor. [2023]

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

Thalamic deep brain stimulation for essential tremor: relation of lead location to outcome. [2008]

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

Thalamic deep brain stimulation for essential tremor: relation of lead location to outcome. [2022]

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

Long-term follow-up of thalamic deep brain stimulation for essential and parkinsonian tremor. [2022]

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

Unilateral thalamic deep brain stimulation for refractory essential tremor and Parkinson's disease tremor. [2019]

7. Austria pubmed.ncbi.nlm.nih.gov

Bilateral thalamic deep brain stimulation for essential tremor in elderly patients. [2019]