Essential TremorTRaNCENCT06293638
Functional Brain Network Changes in Patients Undergoing Deep Brain Stimulation for Essential Tremor
An observational study of Essential Tremor, run by The Cleveland Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Essential Tremor
- What is being tested?
- Alcohol, Alprazolam and Cold Therapy
- Type of treatment
- Medical device, Surgery or procedure
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Mar 2024to 31 Dec 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
Jeff Negrey, MA, 216-636-5504, negreyj2@ccf.org
James Liao, MD
About this study
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.
Read the detailed description
Electrophysiological data from participants will be collected during electroencephalography (EEG) or magnetoencephalography (MEG) procedures. The EEG or MEG experiments will also include recordings from the DBS system that may be synchronized to externally recorded signals (e.g., MEG, EEG, EMG, accelerometry) via gentle tap-induced motion artifacts, and/or by applying a small, barely perceptible electrical current at the skin over the DBS system with use of a transcutaneous electrical nerve stimulation (TENS) unit.
It is hypothesized that the chronic, electrical stimulation of the target region has both local and circuit-wide effects, the net effect of which is to disrupt the pathophysiological neural activity present across both cortical and subcortical brain regions that and thought to underlie disease manifestation (i.e., tremor). By systemically characterizing the pathways involved in propagating tremor-related activity as well as mediating treatment-related benefits, the investigators hope to identify potential new therapeutic targets or treatment paradigms to further optimize tremor control in this population.
- Conditions
- Essential Tremor
- Being tested
- Alcohol, Alprazolam, Cold Therapy, Peripheral Nerve Stimulation
- Keywords
- essential tremor, deep brain stimulation, DBS, ET, tremor, hand tremors
- Medical subject headings
- Essential Tremor, Tremor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlcoholDrug
Also called Vodka
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.
AlprazolamDrug
Also called Xanax
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 TherapyDevice
Also called BREG Polar Care Glacier Cold Therapy System
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 StimulationProcedure or 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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: Alcohol; Drug: Alprazolam; Device: Cold Therapy; Procedure: Peripheral Nerve Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: up to 8 hours in-lab during experiment
Secondary outcomes (3)
Essential tremor severity: Limb acceleration
Accelerometers placed on the limb will measure tremor energy in the 4-12Hz band, in units of mG^2/Hz. Data is 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).
Measured: up to 8 hours in-lab during experiment
Essential tremor severity: Tremor Research Group Essential Tremor Rating Scale (TETRAS)
Numerical clinical tremor assessment scale correlated with severity of tremor. Data is collected 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). Items are scored 0-4 with "0" being normal and "4" being severely abnormal.
Measured: up to 8 hours in-lab during experiment
Essential tremor severity: Grip force
A hand-held force sensor will measure grip force (Newtons). Data is 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).
Measured: up to 8 hours in-lab during experiment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2024
- Study start25 Mar 2024
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Essential TremorStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, James Liao, The Cleveland Clinic
- Investigators
- James Liao, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06293638
- Sponsor's protocol ID
- 23-1125
- Acronym
- TRaNCE
- Status last verified
- Apr 2026
- First submitted
- 30 Jan 2024
- Last updated
- 8 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Brain Network Changes in Patients Undergoing Deep Brain Stimulation for Essential Tremor
- ClinicalTrials.gov ID
- NCT06293638
- Acronym / sponsor ID
- TRaNCE / 23-1125
- Conditions
- Essential Tremor
- Keywords
- essential tremor, deep brain stimulation, DBS, ET, tremor, hand tremors
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- 25 Mar 2024 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 5 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Electrophysiological data from participants will be collected during electroencephalography (EEG) or magnetoencephalography (MEG) procedures. The EEG or MEG experiments will also include recordings from the DBS system that may be synchronized to externally recorded signals (e.g., MEG, EEG, EMG, accelerometry) via gentle tap-induced motion artifacts, and/or by applying a small, barely perceptible electrical current at the skin over the DBS system with use of a transcutaneous electrical nerve stimulation (TENS) unit.
It is hypothesized that the chronic, electrical stimulation of the target region has both local and circuit-wide effects, the net effect of which is to disrupt the pathophysiological neural activity present across both cortical and subcortical brain regions that and thought to underlie disease manifestation (i.e., tremor). By systemically characterizing the pathways involved in propagating tremor-related activity as well as mediating treatment-related benefits, the investigators hope to identify potential new therapeutic targets or treatment paradigms to further optimize tremor control in this population.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Essential Tremor with DBS | – | Drug: Alcohol, Drug: Alprazolam, Device: Cold Therapy, Procedure: Peripheral Nerve Stimulation1. 30-80 years of age 2. Diagnosis of ET 3. Previously implanted with a DBS system for disease management per standard of care |
| Essential Tremor without DBS | – | Drug: Alcohol, Drug: Alprazolam, Device: Cold Therapy, Procedure: Peripheral Nerve Stimulation1. 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 |
| No Known Neurological Disease or Disorder | – | Drug: Alcohol, Drug: Alprazolam, Device: Cold Therapy, Procedure: Peripheral Nerve Stimulation1. 30-80 years of age 2. No known neurological disease or disorder |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (7 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlcoholAlso: VodkaAlcohol 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. | Drug | Essential Tremor with DBS, Essential Tremor without DBS, No Known Neurological Disease or Disorder |
| AlprazolamAlso: XanaxAlprazolam 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. | Drug | Essential Tremor with DBS, Essential Tremor without DBS, No Known Neurological Disease or Disorder |
| Cold TherapyAlso: BREG Polar Care Glacier Cold Therapy SystemOne 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. | Device | Essential Tremor with DBS, Essential Tremor without DBS, No Known Neurological Disease or Disorder |
| Peripheral Nerve StimulationElectrical 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. | Procedure or surgery | Essential Tremor with DBS, Essential Tremor without DBS, No Known Neurological Disease or Disorder |
Primary outcome
CTCM Coherence
Time frame: up to 8 hours in-lab during experiment
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).
Power of oscillatory activity across the CTCM network in response to tremor interventions
Time frame: up to 8 hours in-lab during experiment
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).
3 secondary outcomes
Essential tremor severity: Limb acceleration
Time frame: up to 8 hours in-lab during experiment
Essential tremor severity: Tremor Research Group Essential Tremor Rating Scale (TETRAS)
Time frame: up to 8 hours in-lab during experiment
Essential tremor severity: Grip force
Time frame: up to 8 hours in-lab during experiment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
James Liao, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Essential Tremor, run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jeffrey Negrey, MA (2163166896, negreyj2@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CTCM Coherence (time frame: up to 8 hours in-lab during experiment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2026.