Brain Stimulation for Essential Tremor

Recruiting at 1 trial location

Overseen By Leonardo B Almeida, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Disqualifiers: No essential tremor

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1-2 weeks

12 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. It focuses on brain stimulation for Essential Tremor, so it's best to ask the study team for guidance.

What data supports the effectiveness of the treatment for essential tremor?

Research shows that symmetric biphasic pulses can increase the therapeutic window (range of doses that are effective without causing side effects) in deep brain stimulation for essential tremor, potentially reducing side effects like ataxia (lack of muscle control). Shorter pulse widths may also help reduce side effects, although their long-term benefits need further study. ^{1 2 3 4 5}

Is brain stimulation for essential tremor generally safe?

Research suggests that using symmetric biphasic pulses in brain stimulation for essential tremor may reduce certain side effects compared to other pulse types. However, the long-term safety and effectiveness of these newer stimulation methods need further study. ^{1 2 4 5 6}

How is the treatment 'Active biphasic pulse stimulation' unique for essential tremor?

This treatment uses symmetric biphasic pulses, which can increase the therapeutic window (range of effective doses) and reduce side effects like ataxia (loss of control of body movements) compared to traditional methods. It offers a novel approach by modifying the pulse shape and width, potentially improving effectiveness and minimizing side effects. ^{1 2 4 7 8}

What is the purpose of this trial?

This project aims to investigate novel ways to deliver brain stimulation to Essential Tremor (ET) patients by introducing software changes to their existing devices. The study team aims to investigate safety and efficacy of these new stimulation parameters in patients with ET.

Research Team

Joshua K Wong, MD

Principal Investigator

Univeristy of Florida

Eligibility Criteria

This trial is for people with Essential Tremor who already have a brain stimulation device implanted. They should be mentally sharp (with an MMSE score over 24) and have noticed their tremor control isn't as good as it was after surgery, even on two different check-ups.

Inclusion Criteria

You have undergone deep brain stimulation surgery for essential tremor, and your tremors have not improved as expected after the surgery.

Exclusion Criteria

I have not been diagnosed with Essential Tremor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive active biphasic pulse stimulation through their DBS devices with various settings tested, including Home Settings, VIN Biphasic, and Stimulator Off, with a 30-minute washout period between conditions.

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of tremor severity and gait impairment.

4 weeks

Treatment Details

Interventions

• Active biphasic pulse stimulation---Home Settings
• Active biphasic pulse stimulation---Stimulator Off
• Active biphasic pulse stimulation---VIN Biphasic

Trial Overview The study tests new software settings for the brain stimulation devices in ET patients to see if they can better control tremors. Participants will try three modes: active stimulation at home, active VIN Biphasic stimulation, and periods with the stimulator turned off.

Participant Groups

Group I: Patients with Essential Tremor Experimental Treatment 3 Interventions

Patients with chronically implanted DBS devices for ET who experience progressive worsening of tremor symptoms over time. The DBS implantable pulse generator (IPG) will be loaded with a temporary custom firmware to allow implementation of active biphasic pulse stimulation. The following random conditions will be applied: (1) Home Settings; (2) VIN Biphasic; (3) Stimulator Off. A 30-minute washout period will be applied between each of the random conditions. Therefore, each patient will serve as their own control.

Active biphasic pulse stimulation---Home Settings is already approved in European Union, United States for the following indications:

Approved in European Union as Active biphasic pulse stimulation for:

• Essential Tremor

Approved in United States as Biphasic DBS for:

• Essential Tremor
• Parkinson's Disease
• Dystonia

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

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

Findings from Research

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 involving 12 patients with essential tremor, symmetric biphasic pulses used in deep brain stimulation (DBS) were found to significantly reduce ataxia compared to standard cathodic pulses during a 3-hour stimulation period.

Both pulse shapes provided equivalent tremor control, but biphasic pulses also improved the rate of speech, indicating a potential advantage in minimizing side effects while maintaining therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute stimulation with symmetric biphasic pulses induces less ataxia compared to cathodic pulses in DBS for essential tremor. Boogers, A., Peeters, J., Van Bogaert, T., et al.[2023]

Directional deep brain stimulation (DBS) showed higher side-effect thresholds compared to traditional circular DBS, indicating it may be safer for patients with tremors.

Bipolar DBS with directional anodes resulted in fewer side effects than both monopolar and bipolar circular stimulation, while all stimulation methods provided similar tremor suppression effects just below their side-effect thresholds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bipolar Directional Deep Brain Stimulation in Essential and Parkinsonian Tremor. Steffen, JK., Reker, P., Mennicken, FK., et al.[2022]

In a study involving 9 patients with essential tremor, deep brain stimulation (DBS) using a shorter pulse width of 40 μs resulted in a significantly larger therapeutic window compared to the conventional 60 μs setting, primarily due to higher thresholds for side effects.

Both pulse widths effectively improved tremor symptoms compared to no stimulation, but the 40 μs setting required less energy and activated a smaller volume of neural tissue, suggesting it could be a safer and more efficient option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Less is more - Pulse width dependent therapeutic window in deep brain stimulation for essential tremor. Moldovan, AS., Hartmann, CJ., Trenado, C., et al.[2019]

Short pulse width stimulation (30 μs) initially improved tremor control in 3 patients with essential tremor who were unresponsive to standard deep brain stimulation settings, suggesting a potential widening of the therapeutic window.

However, the benefits of this stimulation technique appeared to diminish during early follow-up, highlighting the importance of assessing long-term outcomes to evaluate its effectiveness in treating essential tremor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endurance of Short Pulse Width Thalamic Stimulation Efficacy in Intention Tremor. Wirth, T., Dayal, V., de Roquemaurel, A., et al.[2021]

In a study involving 28 patients with Parkinson's disease and essential tremor, newer generation deep brain stimulation (DBS) systems showed a significantly greater therapeutic window compared to legacy systems, indicating better control over symptoms with fewer side effects.

Both newer and legacy DBS systems resulted in similar improvements in motor scores and medication reduction after six months, suggesting that while the newer systems offer enhanced programming options, their overall efficacy in symptom management remains comparable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Experience With New Generation Deep Brain Stimulation Leads in Parkinson's Disease and Essential Tremor Patients. Shao, MM., Liss, A., Park, YL., et al.[2022]

The pilot study involving 11 essential tremor patients showed that square biphasic pulse shaping (BiP) significantly improved tremor symptoms compared to both the conventional deep brain stimulation (ClinDBS) and the DBS OFF conditions, with total scores on the Fahn-Tolosa Tremor Rating Scale improving from 28.5 to 16.5 after 3 hours of BiP stimulation.

BiP stimulation was found to be safe and well-tolerated, with no adverse effects reported, indicating its potential as a promising alternative to conventional DBS for treating essential tremor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Square biphasic pulse deep brain stimulation for essential tremor: The BiP tremor study. De Jesus, S., Almeida, L., Shahgholi, L., et al.[2019]

Chronic electrical stimulation of the superior cerebellar peduncle can effectively reduce spasticity and dyskinesias in patients, with effects lasting for days or weeks after stimulation stops.

This method, which is different from the traditional approach targeting the thalamus for essential tremor, may involve changes in synaptic connections, suggesting a potential mechanism of action through reactive synaptogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Different effect of chronic electrical stimulation of the region of the superior cerebellar peduncle and the nucleus ventralis intermedius of the thalamus in the treatment of movement disorders. Galanda, M., Hovath, S.[2018]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

Acute stimulation with symmetric biphasic pulses induces less ataxia compared to cathodic pulses in DBS for essential tremor. [2023]

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

Bipolar Directional Deep Brain Stimulation in Essential and Parkinsonian Tremor. [2022]

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

Less is more - Pulse width dependent therapeutic window in deep brain stimulation for essential tremor. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Endurance of Short Pulse Width Thalamic Stimulation Efficacy in Intention Tremor. [2021]

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

Early Experience With New Generation Deep Brain Stimulation Leads in Parkinson's Disease and Essential Tremor Patients. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Square biphasic pulse deep brain stimulation for essential tremor: The BiP tremor study. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Different effect of chronic electrical stimulation of the region of the superior cerebellar peduncle and the nucleus ventralis intermedius of the thalamus in the treatment of movement disorders. [2018]