Physiology, Imaging and Modeling of Essential Tremor

Not Applicable

Recruiting

• Conditions: Dystonia; Essential Tremor; Parkinson Disease
• Interventions: Device: Active biphasic pulse stimulation---Home Settings; Device: Active biphasic pulse stimulation---VIN Biphasic; Device: Active biphasic pulse stimulation---Stimulator Off

• Registration Number: NCT03811405
• Lead Sponsor: University of Florida

Brief Summary

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.

Detailed Description

Deep brain stimulation (DBS) is a neuromodulatory therapy that is effective in a subset of well selected essential tremor (ET) patients. However, as many as 1/5 of patients may initially improve, but then steadily worsen following the operation. The investigators developed a technique to study a variety of alternative stimulation methods without the use of an invasive repeat surgical intervention.

The electrophysiological effects of non-conventional DBS differ from traditional DBS, however the physiological differences in the setting of human tremor remain largely unknown. This study plans to explore gaps in knowledge of neuromodulation and will collect and contribute essential information to the underlying mechanism of action of DBS. The hypothesis of this project centers around active biphasic stimulation providing a wider therapeutic window and a lower adverse event profile as compared to conventional DBS.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2019-01-17
• Study First Submitted QC: 2019-01-17
• Study First Posted: 2019-01-22
• Study Start: 2021-04-01
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-17
• Last Update Posted: 2024-06-20
• Primary Completion: 2025-06-30
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• Existing unilateral or bilateral VIN DBS for ET, non-demented (MMSE>24), and must have a documented suboptimal tremor suppression on two successive visits (compared to the baseline post-operative improvement at 6 months following ET DBS surgery). For bilateral cases, the most affected tremor side will be studied.

Read More

Exclusion Criteria

• No diagnosis of Essential Tremor

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patients with Essential Tremor	Active biphasic pulse stimulation---VIN Biphasic	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.
Patients with Essential Tremor	Active biphasic pulse stimulation---Home Settings	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.
Patients with Essential Tremor	Active biphasic pulse stimulation---Stimulator Off	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.

Primary Outcome Measures

Name	Time	Method
Volume of tissue activated from stimulation with ET DBS	up to 24 hours	The study team will use computer simulation and virtual reconstruction of the brain from pre-operative MRI data to calculate the volume of tissue activated (VTA) from the novel stimulation patterns. The investigators will assess the feasibility of the patterns to address the worsening of ET that may occur in 20% or more of the ET population.
Baseline DBS settings versus active biphasic pulse DBS settings	up to 1 hour	The investigators will compare the degree of tremor suppression from the most optimal DBS settings that can be obtained via traditional programming methods versus active biphasic DBS. The degree of tremor will be quantified by multiple clinical metrics including the Fahn-Tolosa-Marin Tremor Rating Scale and Kinesia ONE® accelerometer system.

Secondary Outcome Measures

Name	Time	Method
Tremor motor physiology	up to 15 minutes	Essential tremor motor physiology will be recorded by the Kinesia ONE accelerometer system. THe Kinesia ONE system is a wireless wearable motion sensor unit and portable transducer that translates the degree of movement into a standardized scale. Tremor physiology will be assessed for the various DBS settings.
The Fahn-Tolosa-Marin Tremor Rating Scale	up to 15 minutes	Essential tremor severity will be assessed by the clinically validated Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS). It is a 0 to 4 scale (0 = no tremor; 4 = severe amplitude of tremor) of 9 different parts of the body. The FTMTRS will be assessed for the various DBS settings.
Gait impairment	up to 15 minutes	Essential tremor's effect on gait will be assessed by the GAITRite system. Patients will walk along a GAITRite floor mat to have the various gait parameters such as step time, cycle time, step length, stride length, etc measured. Gait parameters will be assessed on the various DBS settings.

Trial Locations

Locations (2)

UF Health at the University of Florida; 🇺🇸 Gainesville, Florida, United States

McKnight Brain Institute--Fixel Center for Neurological Diseases; 🇺🇸 Gainesville, Florida, United States