Essential Tremor > Directional Bilateral Thalamic Patterned Stimulation

DBS Programming for Essential Tremor

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Alfonso Fasano

Must be taking: Anti-tremor medication

Disqualifiers: Psychiatric condition, Depression, Drug abuse, others

No Placebo Group

Approved in 3 jurisdictions

Trial Summary

What is the purpose of this trial?

Population Size and Eligible Patients: The investigators aim to recruit 5 to 10 patients with tremors who have previously undergone Ventral Intermedius Deep Brain Stimulation (VIM-DBS) treatment but have experienced early or late loss of benefits. Additionally, the investigators will enroll ten patients with essential tremor who require VIM-DBS surgery. These individuals will undergo bilateral implantation of Boston Scientific Genus Implantable Pulse Generator (IPG) devices, connected to Boston Scientific Cartesia™ 8-contact Directional Leads. Study Design: This study comprises two distinct phases. Phase 1 is a cross-sectional investigation designed to identify the optimal algorithm for patterned stimulation in the VIM region . Phase 2 is a prospective clinical trial focusing on the assessment of safety and efficacy of bilateral VIM-DBS in patients with essential tremor. Objectives: The primary objective in Phase 2 is to evaluate the safety and effectiveness of bilateral VIM-DBS in individuals with essential tremor. In Phase 1, the investigators seek to explore the impact of the Chronos programming software on tremor patients who have experienced early or late loss of benefits.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of your anti-tremor medication for at least 4 weeks before screening. So, you should not stop taking your current medications.

What data supports the effectiveness of the treatment Directional Bilateral Thalamic Patterned Stimulation for Essential Tremor?

Research suggests that using directional current steering and short pulse stimulation in the thalamus can reduce side effects in essential tremor patients, indicating potential benefits of this approach. Additionally, symmetric biphasic pulses, which are part of the treatment, have been shown to enlarge the therapeutic window, potentially improving effectiveness.

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Is DBS programming for essential tremor generally safe in humans?

Deep brain stimulation (DBS) for essential tremor has been studied for long-term safety, showing that while it can be effective, there are risks such as mild side effects that can be managed with adjustments, and device-related complications that may require additional surgeries. Some patients experienced asymptomatic brain bleeds and seizures, but these were not common.

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How is the Directional Bilateral Thalamic Patterned Stimulation treatment different from other treatments for essential tremor?

This treatment is unique because it uses directional and short-pulse deep brain stimulation (DBS) in the thalamus to potentially improve tremor symptoms while reducing side effects, unlike traditional DBS which may not offer these specific benefits.

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Eligibility Criteria

This trial is for patients with tremors, specifically those who have had VIM-DBS treatment but lost its benefits and those needing new VIM-DBS surgery. Up to 20 people will be enrolled, all of whom must have essential tremor and agree to receive a specific device implant.

Inclusion Criteria

Written and signed Informed Consent

I am an Essential Tremor patient needing Deep Brain Stimulation surgery.

Soft signs (categorizing patients as ET-plus) will be allowed and noted in the patient's chart

Exclusion Criteria

Presence of significant psychiatric or cognitive condition likely to compromise the subject's ability to comply with requirements of the study protocol

Any current drug or alcohol abuse, as determined by the investigator

Unwilling or inability to follow the procedures specified by the protocol

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 - Cross-sectional Investigation

Identify the optimal algorithm for patterned stimulation in the VIM region for patients with early or late loss of benefits from previous VIM-DBS treatment.

6 months

Baseline measurement before IPG replacement

Phase 2 - Prospective Clinical Trial

Assessment of safety and efficacy of bilateral VIM-DBS in patients with essential tremor, with programming in four different settings over 8 months.

8 months

Baseline, Month 2, Month 4, Month 6, Month 8

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The study tests a DBS programming method using the Chronos software in two phases: first, finding the best stimulation pattern for tremor control; second, evaluating safety and effectiveness of this approach in new patients requiring bilateral VIM deep brain stimulation.

Group I: Phase 2 Experimental Treatment 1 Intervention

Ten patients with ET needing DBS-VIM surgery will be recruited and will receive Boston Scientific Genus IPG bilaterally connected to Boston Scientific Cartesia™ 8-contact Directional Leads. The programming will be done in four different settings/periods during the course of 8 months.

Group II: Phase 1 Experimental Treatment 1 Intervention

5 to 10 patients with tremor already treated with VIM-DBS but not doing well because of early or late loss of benefits will be recruited by the PI over a 6 months period. If interested, the potential participants will be screened, informed, and consented by a research coordinator. Before the replacement of their IPG (implantable pulse generator), a baseline measurement will be performed.

Directional Bilateral Thalamic Patterned Stimulation is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as VIM-DBS for:

• Essential Tremor
• Parkinsonian Tremor

🇪🇺 Approved in European Union as VIM-DBS for:

• Essential Tremor
• Parkinsonian Tremor
• Dystonic Tremor

🇨🇦 Approved in Canada as VIM-DBS for:

• Essential Tremor
• Parkinsonian Tremor

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Movement Disorders Centre - Toronto Western Hospital Toronto, Canada

Who Is Running the Clinical Trial?

Alfonso Fasano Lead Sponsor

Boston Scientific Corporation Industry Sponsor

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] Symmetric biphasic pulses enlarge the therapeutic window in thalamic deep brain stimulation in patients with essential tremor. Adding an interphase gap to these symmetric biphasic pulses may further affect the therapeutic window.

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

Bipolar Directional Deep Brain Stimulation in Essential and Parkinsonian Tremor. [2022] To compare directional monopolar, bipolar, and directional bipolar thalamic deep brain stimulation (DBS) in tremor patients.

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

Thalamic short pulse stimulation diminishes adverse effects in essential tremor patients. [2019] To investigate the effect of directional current steering and short pulse stimulation in the ventral intermediate thalamic nucleus (VIM) on stimulation-induced side effects in patients with essential tremor.

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

Benefits and Risks of a Staged-Bilateral VIM Versus Unilateral VIM DBS for Essential Tremor. [2022] Despite over 30 years of clinical experience, high-quality studies on the efficacy of bilateral versus unilateral deep brain stimulation (DBS) of the ventral intermediate (VIM) nucleus of the thalamus for medically refractory essential tremor (ET) remain limited.

5. England pubmed.ncbi.nlm.nih.gov

Utilization of predefined stimulation groups by essential tremor patients treated with VIM-DBS. [2022] To identify the utilization and general acceptance of switching between predefined stimulation groups in essential tremor (ET) patients treated with deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus.

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

Long-term safety and efficacy of unilateral deep brain stimulation of the thalamus in essential tremor. [2022] Our objective was to investigate the long-term safety and efficacy of unilateral deep brain stimulation (DBS) of the VIM nucleus of the thalamus in essential tremor. Forty-nine patients were evaluated for DBS between December 1993 and March 1998. Tremor was assessed by a clinical rating scale at 3 and 12 months and then yearly. Three patients were not implanted, seven were explanted prior to 24 months, 11 were lost to long-term follow-up, and three died from unrelated causes. Twenty-five patients were evaluated with follow-up greater than or equal to 2 years. The last postsurgical follow-up occurred on average 40.2 +/- 14.7 months after surgery. Tremor scores were significantly improved with stimulation on at the long-term follow-up as compared to baseline. There was no change in tremor scores from baseline to long-term follow-up with stimulation off. There was no significant change in any stimulus parameters from 3 months to the long-term follow-up. Three patients had asymptomatic intracerebral hemorrhages and one patient had postoperative seizures. Stimulus-related adverse reactions were mild and easily controlled with changes in stimulus parameters. Device-related complications were common and required repeated surgical procedures. Unilateral DBS of the thalamus has long-term efficacy in some patients for treatment of essential tremor. However, this therapy is compromised by loss of efficacy in some patients and device complications which increase the risk of additional surgical procedures.

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

Unilateral thalamic deep brain stimulation for refractory essential tremor and Parkinson's disease tremor. [2019] To determine the efficacy and tolerability of unilateral thalamic deep brain stimulation (DBS) for patients with medically refractory essential tremor (ET) and the tremor associated with Parkinson's disease (PD).

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

Combined Short-Pulse and Directional Deep Brain Stimulation of the Thalamic Ventral Intermediate Area for Essential Tremor. [2023] Novel deep brain stimulation (DBS) systems allow directional and short-pulse stimulation to potentially improve symptoms and reduce side effects. The aim of this study was to investigate the effect of short-pulse and directional stimulation, in addition to a combination of both, in the ventral intermediate thalamus (VIM)/posterior subthalamic area (PSA) on tremor and stimulation-induced side effects in patients with essential tremor.

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

Comparison of tractography-assisted to atlas-based targeting for deep brain stimulation in essential tremor. [2019] Direct targeting of the dentato-rubro-thalamic tract is efficacious in DBS for tremor suppression.