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

Essential Tremor Clinical Trial

— TRaNCE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06293638
• Other study ID #: 23-1125
• Status: Recruiting
• Start date: March 25, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2024
• Source: The Cleveland Clinic
• Contact: Jeffrey Negrey, MA
• Phone: 2163166896
• Email: negreyj2[@]ccf.org
• Is FDA regulated: No
• Study type: Observational

Clinical 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. Participants will be asked to 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 1) cooling the limb, 2) oral administration of alprazolam, 3) oral consumption of ethanol (alcohol), or 4) peripheral nerve stimulation.

Description:

Electrophysiological data from participants will be collected during Magnetoencephalography (MEG) procedures. The MEG experiments, will utilize 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• Between 40 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.

Exclusion Criteria:

• Secondary Parkinsonism, stroke, or progressive central nervous system disease other than ET;
• 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 will be excluded from any alcohol administration.

Related Conditions & MeSH terms

• Essential Tremor
• Tremor

Intervention

Drug:
• Alcohol
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
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.

Device:
• Cold Therapy
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.

Procedure:
• Peripheral Nerve Stimulation
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.

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.	up to 8 hours in-lab during experiment
Secondary	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).	up to 8 hours in-lab during experiment
Secondary	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).	up to 8 hours in-lab during experiment