Deep Brain Stimulation for Essential Tremor

Overseen By Johanna Caskey

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to deep brain stimulation (DBS) for individuals with essential tremor (ET), a condition that causes uncontrollable shaking. The study examines a method called coordinated reset DBS (CR-DBS), which uses different patterns of stimulation at lower currents to determine if it is safer and more effective than traditional DBS. Participants will receive either the new CR-DBS treatment or the standard DBS to compare outcomes. The trial seeks individuals diagnosed with essential tremor who have undergone a specific type of MRI scan and are implanted with a certain DBS system. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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 prior data suggests that this device is safe for treating Essential Tremor?

Research has shown that traditional deep brain stimulation (DBS) can cause side effects such as slurred speech, numbness, partial paralysis, and headaches. Researchers are studying a newer method, Coordinated Reset DBS (CR-DBS), to determine if it might result in fewer side effects. This method uses different patterns of stimulation at lower levels, which may help reduce these risks.

One study found that the side effects of CR-DBS were generally mild and similar to those with traditional DBS. Specifically, about 11% of patients experienced slurred speech, 6% had numbness or partial paralysis, and 7% reported headaches.

In the current study, researchers are testing CR-DBS to ensure its safety and effectiveness. As this is an early-phase study, the primary focus is on ensuring the treatment's safety for people with Essential Tremor. This step is common in the initial testing of any new treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Coordinated Reset Deep Brain Stimulation (CR-DBS) for Essential Tremor because it offers a new way to tackle the condition. Unlike traditional DBS, which continuously stimulates the brain, CR-DBS uses a patterned stimulation technique designed to disrupt the abnormal brain activity causing tremors. This approach could potentially reduce side effects and improve precision in targeting tremor-related brain circuits. As a result, CR-DBS might provide more effective and tailored symptom relief for patients with essential tremor.

What evidence suggests that this trial's treatments could be effective for Essential Tremor?

Research has shown that Coordinated Reset Deep Brain Stimulation (CR-DBS), one of the treatment arms in this trial, might help people with Essential Tremor (ET). Studies have found that CR-DBS can improve movement problems by altering brain signals in a specific way. For example, some patients experienced a 29.4% improvement in their movement scores after just five days of CR-DBS. This suggests that CR-DBS might control tremors using less stimulation than traditional methods, which are being tested in another arm of this trial. These results are encouraging, but more research is needed to confirm the long-term benefits. ^{1 2 3 6 7}

Who Is on the Research Team?

Jing Wang, PhD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05897775

Coordinated Reset Deep Brain Stimulation for Essential ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8397098/

Deep Brain Stimulation for Tremor: Update on Long-Term ... This study showed PSA-DBS to be more efficient, compared to Vim-DBS, providing similar tremor control with lower stimulation amplitudes.

3. withpower.com withpower.com/trial/deep-brain-stimulation-for-essential-tremor-a6e28

Deep Brain Stimulation for Essential Tremor This Phase 1 medical study run by University of Minnesota is evaluating whether Coordinated Reset Deep Brain Stimulation will have tolerable side effects ...

4. frontiersin.org frontiersin.org/journals/neuroinformatics/articles/10.3389/fninf.2023.1185723/full

Effect of subthalamic coordinated reset deep brain ... Changes in the mUPDRS score showed gradual improvement during 5 days of STN CR DBS, reaching an improvement of 29.4% from the baseline on CR day ...

5. nature.com nature.com/articles/s41531-024-00797-w

npj Parkinson's Disease We found that subthalamic CR DBS suppressed subthalamic and cortical-subthalamic coherences in the beta band, correlating with motor improvements.

6. jneurosci.org jneurosci.org/content/43/45/7575

Advances in Deep Brain Stimulation: From Mechanisms to ... A 2016 study validated the acute benefits of CR DBS and a carryover effect of up to 2 weeks on a wider range of parkinsonian symptoms, including ...

7. studyfinder.umn.edu studyfinder.umn.edu/studies/31423

Coordinated Reset Deep Brain Stimulation for Essential ... We are studying the possibility that a kind of deep brain stimulation called "coordinated reset" stimulation (CR-DBS) will be more effective than current DBS ...