About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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

Disqualifiers

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;

Trial population

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

Trial design

Design model

Case-control

Time perspective

Prospective

Treatments tested in this trial

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.
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.
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.
Peripheral Nerve Stimulation
Procedure/Surgery
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.

Treatment groups

55 Participants

are divided into 3 treatment groups

Group A: Essential Tremor with DBS4 interventions

Group B: Essential Tremor without DBS4 interventions

Group C: No Known Neurological Disease or Disorder4 interventions

Trial outcomes

Primary outcomes

1

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).

Time frame