Functional Brain Network Changes in Patients Undergoing Deep Brain Stimulation for Essential Tremor

NCT06293638 | Recruiting

• 1 other identifier: 23-1125
• Study Type: observational
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to collect electrophysiological data related to functional brain network changes in patients undergoing deep brain stimulation for the treatment of essential tremor. Participants will either 1) have electroencephalography (EEG) scalp electrodes placed, or 2) remain seated with their head inside of a magnetoencephalography (MEG) recording system, as resting-state and task-related data are acquired. Spontaneous electrophysiological activity will be recorded in both the eyes open and eyes closed conditions with the participant seated comfortably. These recordings will be repeated in the DBS OFF and DBS ON states, with the ON state involving specific settings identified as optimal, sub-optimal, or ineffective at achieving tremor control. They will also be repeated following the optional administration non-DBS tremor mitigation techniques, which may include one or more of the following: 1) cooling the limb, 2) oral administration of alprazolam, 3) oral consumption of ethanol (alcohol), or 4) peripheral nerve stimulation.

Conditions

Essential Tremor

Keywords

essential tremor; deep brain stimulation; DBS; ET; tremor; hand tremors

Outcome Measures

Primary Outcomes (2)

• CTCM Coherence

  Coherence, a unitless measure of correlation between signals, calculated across the cerebellothalmocorticomuscular (CTCM) circuit, will be computed from neurophysiological recordings including electroencephalography (EEG), electromyography (EMG), magnetoencephalography (MEG), and/or local field potential (LFP), using data collected at rest, during tremor-eliciting tasks, with DBS OFF, with DBS ON (when available), and when using non-DBS tremor interventions (limb cooling and/or peripheral nerve stimulation and/or alprazolam or alcohol).

  up to 8 hours in-lab during experiment

• Power of oscillatory activity across the CTCM network in response to tremor interventions

  Power of tremor-related oscillatory activity, in the form of mean power in the 4-12Hz frequency band with units in mV\^2, will be computed from neurophysiological recordings including electroencephalography (EEG), electromyography (EMG), magnetoencephalography (MEG), and/or local field potential (LFP), using data collected at rest, during tremor-eliciting tasks, with DBS OFF, with DBS ON (when available), and when using non-DBS tremor interventions (limb cooling and/or peripheral nerve stimulation and/or alprazolam or alcohol).

  up to 8 hours in-lab during experiment

Secondary Outcomes (3)

• Essential tremor severity: Limb acceleration

  up to 8 hours in-lab during experiment

• Essential tremor severity: Tremor Research Group Essential Tremor Rating Scale (TETRAS)

  up to 8 hours in-lab during experiment

• Essential tremor severity: Grip force

  up to 8 hours in-lab during experiment

Study Arms (3)

Essential Tremor with DBS

1. 30-80 years of age 2. Diagnosis of ET 3. Previously implanted with a DBS system for disease management per standard of care

Drug: Alcohol; Drug: Alprazolam; Device: Cold Therapy; Procedure: Peripheral Nerve Stimulation

Essential Tremor without DBS

1. 30-80 years of age 2. Diagnosis of ET 3. Has not been previously implanted with a DBS system for disease management per standard of care

Drug: Alcohol; Drug: Alprazolam; Device: Cold Therapy; Procedure: Peripheral Nerve Stimulation

No Known Neurological Disease or Disorder

1. 30-80 years of age 2. No known neurological disease or disorder

Drug: Alcohol; Drug: Alprazolam; Device: Cold Therapy; Procedure: Peripheral Nerve Stimulation

Interventions

Alcohol DRUG

Alcohol consumption is shown to reduce tremor in individuals with essential tremor. The alcoholic beverage will be dispensed by the a clinician study investigator, and the participant will be administered the alcoholic beverage until their tremor is decreased, as determined by the clinician. Individual sensitivity to the tremor-mitigating effects of alcohol varies, but it is anticipated that only light (1-2 40% ABV drinks, containing 1-2 units of absolute alcohol \[10 mL. or 8 g of pure ethanol\]) consumption will be necessary. Participants will then repeat motor task and data collection while the alcohol is effective at controlling tremor, beginning approximately 15-20 minutes after consumption.

Also known as: Vodka

Essential Tremor with DBS; Essential Tremor without DBS; No Known Neurological Disease or Disorder

Alprazolam DRUG

Alprazolam is shown to reduce tremor in individuals with essential tremor. The primary investigator will select the appropriate dose for the patient (0.5mg for patients with a body weight of up to 75kg, and 0.75mg for participants with a body weight of 75kg and higher). Participants will swallow the drug with a glass of water in the presence of the research team. If participants have not reached a sufficient level of tremor improvement, a subsequent dose of up to a total of 1.0mg of alprazolam per participant will be requested. Participants will then repeat motor task and data collection.

Also known as: Xanax

Essential Tremor with DBS; Essential Tremor without DBS; No Known Neurological Disease or Disorder

Cold Therapy DEVICE

One or both of the participant's upper limbs will be wrapped with pre-chilled ice packs or a cold water circulating device such as a cryomanchet (e.g., the Breg PolarCare Glacier), and the skin temperature monitored until it lowers to 15-25°C. Participants will then repeat motor task and data collection while the limb is cool.

Also known as: BREG Polar Care Glacier Cold Therapy System

Essential Tremor with DBS; Essential Tremor without DBS; No Known Neurological Disease or Disorder

Peripheral Nerve Stimulation PROCEDURE

Electrical stimulation will be applied using techniques similar to those applied during standard somatosensory evoked potential testing. Specifically, adhesive surface electrodes will be placed above the median and radial nerves at the wrist. Stimulation paradigms will be tailored to each participant based on the frequency characteristics of their tremor. Participants will receive between 20-60 minutes of stimulation, then will repeat motor task and data collection. Transcutaneous peripheral nerve stimulation may help mitigate tremor, with effects lasting beyond cessation of stimulation1-3.

Essential Tremor with DBS; Essential Tremor without DBS; No Known Neurological Disease or Disorder

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be selected from the known patient population from a large research medical center located in a medium-to-large American city.

You may qualify if:

• Between 30 and 80 years of age;
• Ability to provide informed consent;
• Clinical diagnosis of ET by a movement disorders neurologist with a disease duration of at least 3 years and being treated with a DBS; OR
• Clinical diagnosis of ET by a movement disorders neurologist with a disease duration of at least 3 years and not being treated with a DBS; OR
• No known neurological disease or disorder.

You may not qualify if:

• The individual has a condition that, in the opinion of the investigator, would significantly increase the risk for interference with study compliance, safety, or outcome;
• Presence of active psychiatric symptoms meeting Diagnostic and Statistical Manual of Mental Disorders-4th Edition (DSM-IV) criteria for Axis-I disorder on formal psychiatric evaluation other than depression or anxiety;
• History of cognitive impairment meeting Diagnostic and Statistical Manual of Mental Disorders-4th Edition (DSM-IV) criteria for dementia on formal neuropsychological evaluation, as documented in chart;
• Lack of English-language fluency which would interfere with the ability to understand the study consenting process and potential study risks;
• Hearing or visual impairment precluding testing;
• Motor impairment impacting test responses (i.e., orthopedic injury or disease);
• Anyone currently taking medications with Antabuse-like effects (e.g. Flagyl, Bactrim, Tindamax) will be excluded from any alcohol administration.

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

MeSH Terms

Conditions

Essential Tremor; Tremor

Interventions

Ethanol; Alprazolam; Cryotherapy

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• James Liao, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeffrey Negrey, MA

CONTACT

2163166896; negreyj2@ccf.org

Madeline Porter

CONTACT

2167691866; porterm11@ccf.org

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 30, 2024
• First Posted: March 5, 2024
• Study Start: March 25, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)