Physiology, Imaging and Modeling of Essential Tremor

Physiology, Imaging and Modeling of Deep Brain Stimulation for Essential Tremor

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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Dystonia; Essential Tremor
• Intervention / Treatment: Device: Active biphasic pulse stimulation---Home Settings; Device: Active biphasic pulse stimulation---VIN Biphasic; Device: Active biphasic pulse stimulation---Stimulator Off

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.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Leonardo B Almeida, MD; Phone Number: (352) 294-5400; Email: Leonardo.BritodeAlmeida@neurology.ufl.edu
• Study Contact Backup: Name: Joshua K Wong, MD; Phone Number: (352) 294-5400; Email: joshua.wong@neurology.ufl.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • UF Health at the University of Florida
    • Gainesville, Florida, United States, 32611
      • Not yet recruiting
      • McKnight Brain Institute--Fixel Center for Neurological Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Exclusion Criteria:

• No diagnosis of Essential Tremor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients with Essential Tremor; 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.

Device: Active biphasic pulse stimulation---Home Settings; During this visit, the DBS implantable pulse generator (IPG) will be loaded with a temporary custom firmware to allow implementation of active biphasic pulse stimulation.; Device: Active biphasic pulse stimulation---VIN Biphasic; During this visit, the DBS implantable pulse generator (IPG) will be loaded with a temporary custom firmware to allow implementation of active biphasic pulse stimulation.; Device: Active biphasic pulse stimulation---Stimulator Off; During this visit, the DBS implantable pulse generator (IPG) will be loaded with a temporary custom firmware to allow implementation of active biphasic pulse stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volume of tissue activated from stimulation with ET DBS	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.	up to 24 hours
Baseline DBS settings versus active biphasic pulse DBS settings	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.	up to 1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Fahn-Tolosa-Marin Tremor Rating Scale	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.	up to 15 minutes
Tremor motor physiology	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.	up to 15 minutes
Gait impairment	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.	up to 15 minutes

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Medtronic
• Investigators: Principal Investigator: Leonardo B Almeida, MD, Univeristy of Florida

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: January 17, 2019
• First Posted (Actual): January 22, 2019

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Deep Brain Stimulation (DBS); ventralis intermedius nucleus (VIN); implantable pulse generator (IPG); Diffusion Tensor Imaging (DTI)
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyskinesias; Parkinson Disease; Dystonia; Tremor; Essential Tremor
• Other Study ID Numbers: IRB201802397 -N -A; OCR19607 (Other Identifier: UF OnCore); MEDTRONIC INC (Other Identifier: AGR00011004); 5R25NS108939-04 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes