Directional Bilateral Thalamic Patterned Stimulation (Chronos)

Directional Bilateral Thalamic Patterned Stimulation in Individuals with Essential Tremor

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.

Study Overview

• Status: Recruiting
• Conditions: Essential Tremor
• Intervention / Treatment: Other: DBS programing

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Recruiting
      • Movement Disorders Centre - Toronto Western Hospital
      • Contact: Alfonso Fasano, MD, PhD; Phone Number: 5961 (416) 603-5800; Email: alfonso.fasano@uhn.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Phase 1: 5 to 10 tremor patients already treated with VIM-DBS but not doing well due to early and/or late loss of benefits (i.e. tremor scores ON stimulation identical or greater than before surgery in absence of stimulation).
2. Phase 2: 10 Essential Tremor patients in need of DBS surgery.
3. Written and signed Informed Consent.
4. Age 18 to 85 years old.
5. Subject must have Essential Tremor, as defined by all the following criteria: (a) isolated tremor syndrome consisting of bilateral action tremor; (b) at least three years duration; and (c) with or without tremor in other locations (e.g., head, voice, or low limbs) [1].
6. Soft signs (categorizing patients as Essential Tremor-plus) will be allowed and noted in the patient's chart.
7. Subject must be on stable dose of anti-tremor medication for at least 4 weeks prior to screening.
8. Subject had no botulinum injection for at least three months prior to screening.
9. Subject does not have a significant other medical condition biasing the study finding in investigator's opinion.

Exclusion Criteria:

1. Unwilling or inability to follow the procedures specified by the protocol.
2. Presence of significant psychiatric or cognitive condition likely to compromise the subject's ability to comply with requirements of the study protocol.
3. Untreated clinically significant depression.
4. Any current drug or alcohol abuse, as determined by the investigator.
5. History of suicidal attempt within the last 1 year prior to consent or current active suicidal ideation as determined by the investigator.
6. Any significant medical condition that is likely to interfere with study procedures or likely to confound evaluation of study endpoints.
7. Any terminal illness with life expectancy of < 12 months.
8. Participation in any other interventional clinical trial (e.g. drug, device).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1; 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.	Other: DBS programing; The physician will utilize the Boston Scientific Chronos Clinician Programmer (software) to make adjustments to the Deep Brain Stimulation (DBS) settings for the patients.
Experimental: Phase 2; 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.	Other: DBS programing; The physician will utilize the Boston Scientific Chronos Clinician Programmer (software) to make adjustments to the Deep Brain Stimulation (DBS) settings for the patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tremor Rating Scale (Part A-B)	Range from 0-46. with 0 representing no tremor and 46 representing severe tremor.	Phase 1-Baseline
Tremor analysis	Using accelerometers	Phase 1-Baseline
Tremor Rating Scale (A-C)	Range from 0-46. with 0 representing no tremor and 46 representing severe tremor.	Phase 2-Baseline, Month 2, Month 4, Month 6, Month 8
Quality of life in Essential Tremor Questionnaire (QUEST)	Range from 0-40, with 0 representing no tremor and 40 representing severe tremor.	Phase 2-Baseline, Month 2, Month 4, Month 6, Month 8
Speech analysis	automated analysis pipeline in MatLab	Phase 2-Baseline, Month 2, Month 4, Month 6, Month 8
Tremor analysis (meter per second squared)	Using accelerometers	Phase 2-Baseline, Month 2, Month 4, Month 6, Month 8
Gait speed (meter per second)	Gait Analysis	Phase 2-Baseline, Month 2, Month 4, Month 6, Month 8
Base of support (meter)	Gait Analysis	Phase 2-Baseline, Month 2, Month 4, Month 6, Month 8
Step length (meter)	Gait Analysis	Phase 2-Baseline, Month 2, Month 4, Month 6, Month 8
Stride length (meter)	Gait Analysis	Phase 2-Baseline, Month 2, Month 4, Month 6, Month 8
Single stance time and double stance time (seconds)	Gait Analysis	Phase 2-Baseline, Month 2, Month 4, Month 6, Month 8
Tandem gait	Gait Analysis	Phase 2-Baseline, Month 2, Month 4, Month 6, Month 8
Posturography (newtons)	Using Proteokinetics Zeno System	Phase 2-Baseline, Month 2, Month 4, Month 6, Month 8

Collaborators and Investigators

• Sponsor: Alfonso Fasano
• Collaborators: Boston Scientific Corporation

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 22, 2024

Study Record Updates

• Last Update Posted (Estimated): November 4, 2024
• Last Update Submitted That Met QC Criteria: October 31, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Deep Brain Stimulation; Chronos Physician Programmer
• Additional Relevant MeSH Terms: Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Dyskinesias; Tremor; Essential Tremor
• Other Study ID Numbers: 22-5772

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No