Brain Stimulation for Essential Tremor

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new methods of delivering brain stimulation to assist individuals with Essential Tremor (ET). Researchers aim to determine if modifying the software in existing devices can safely and effectively reduce tremors. Participants will experiment with different settings on their brain stimulation devices, such as Active biphasic pulse stimulation, to identify the most effective option. This trial may suit individuals who already have a brain stimulator for ET but continue to experience worsening tremors. As an unphased trial, it offers participants the chance to explore innovative treatment options that could enhance their quality of life.

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 prior data suggests that these brain stimulation techniques are safe for Essential Tremor patients?

Research has shown that active biphasic pulse stimulation is a safe treatment for people with Essential Tremor (ET). In one study, seven patients received this treatment for a week and reported no negative effects. Another study with ten participants also found the treatment safe and easy to handle, with no serious side effects. These results suggest that the treatment is generally well-tolerated in humans, based on current research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this treatment for essential tremor because it uses active biphasic pulse stimulation, a novel approach compared to the usual continuous deep brain stimulation (DBS). Unlike standard DBS, this method involves different stimulation settings, including a "Home" setting, a "VIN Biphasic" setting, and a "Stimulator Off" period, allowing for personalized adjustments based on patient response. The innovative aspect is the temporary custom firmware that enables these varied stimulation patterns, potentially offering more effective tremor control and improved quality of life for patients who haven't fully benefited from traditional DBS.

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

Research has shown that a new method called active biphasic pulse stimulation may help treat Essential Tremor (ET). In this trial, participants will experience different conditions of this stimulation: Home Settings, VIN Biphasic, and Stimulator Off. Studies have found that this type of stimulation can ease symptoms in ET patients by widening the range of effective treatment, potentially making it more effective than standard options. One study found that biphasic stimulation is safe and can significantly reduce symptoms. Compared to other deep brain stimulation methods, biphasic pulses can offer similar or even better improvements. These findings suggest that biphasic stimulation could be a helpful treatment for people with ET. ^{1 2 4 6 7}

Who Is on the Research Team?

Joshua K Wong, MD

Principal Investigator

Univeristy of Florida

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10933042/

Active recharge biphasic stimulation for the intraoperative ... Compared to conventional passive recharge DBS systems, it has been shown that biphasic stimulation can deliver comparable clinical improvement.

2. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1366227/full

Testing of symmetric biphasic stimulation in Vim-DBS ET ... Symmetric biphasic pulses have been shown to increase the therapeutic window compared to standard cathodic pulses in ET Vim-DBS patients.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11076781/

Testing of symmetric biphasic stimulation in Vim-DBS ET ... Symmetric biphasic pulses have been shown to increase the therapeutic window compared to standard cathodic pulses in ET Vim-DBS patients.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1353802023000512

Double blind, nonrandomized crossover study of active ... In this pilot study, we demonstrated that biphasic DBS is a novel stimulation paradigm which can be administered safely. The biphasic waveform revealed a ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04658641

Characterization of Complex Pulse Shapes in Deep Brain ... Another recent study examined the effect of an active symmetric biphasic pulse in 8 PD and 3 ET patients. They found that this pulse shapes produced significant ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7174089/

Deep Brain Stimulation in Essential Tremor: Targets, ... After 70 months of follow-up, the degree of tremor reduction compared to preoperative baseline was 50%, 34%, and 45% for the same three patient ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X22000171

Anodic and symmetric biphasic pulses enlarge the ... The aim of this study was to investigate the effect of anodic and symmetric biphasic pulses on TW in Vim-DBS ET patients and compare this to the standard ...