Essential tremor is the most common movement disorder worldwide, causing rhythmic shaking most often of the hands, but also the head, voice, and legs. Although not life-threatening, it can severely impair daily activities such as writing, eating, and working. It tends to progress slowly over years and is frequently misdiagnosed as early Parkinson's disease.
What's actually going on in research
Propranolol and primidone remain first-line medications but provide only partial relief for many patients. Focused ultrasound thalamotomy is now FDA-cleared for treatment-resistant hand tremor and offers lasting improvement without open surgery. Trials are evaluating non-invasive focused ultrasound approaches, new DBS targets, and oral agents including T-type calcium channel blockers and GABA modulators. There is also growing interest in whether essential tremor represents a degenerative cerebellar condition rather than a purely functional one.
Focused ultrasound advances
Incisionless MRI-guided focused ultrasound thalamotomy is FDA-cleared for disabling hand tremor and is being studied for bilateral application and voice tremor, expanding its potential use.
New oral medications
T-type calcium channel blockers such as CX-8998 and GABA-B modulators are in clinical trials aiming to reduce tremor amplitude more effectively than existing medications with fewer side effects.
Closed-loop DBS
Adaptive deep brain stimulation that senses tremor-related brain signals and adjusts stimulation accordingly is in early trials for essential tremor, aiming to reduce side effects and battery use.
What to know before you search
Eligibility depends on tremor severity, prior medication trials, surgical candidacy, and whether tremor is isolated or associated with another neurological condition.
What types of trials are currently open
- Focused ultrasound trials — Testing bilateral and extended-indication focused ultrasound thalamotomy for hand and voice tremor.
- Oral medication trials — Evaluating T-type calcium channel blockers and GABA modulators as new first- or second-line drugs.
- Adaptive DBS trials — Closed-loop deep brain stimulation systems that sense and respond to tremor in real time.
- Non-invasive stimulation trials — Transcranial alternating current stimulation and repetitive TMS as non-surgical tremor reduction approaches.
- Disease mechanism studies — Investigating cerebellar neurodegeneration as an underlying cause to identify new treatment targets.
Recently added Essential Tremor trials
Closed-loop TMS for Tremor
This study investigates the potential of phase-locked transcranial magnetic stimulation (TMS) as a non-invasive intervention for tremor in patients with Essential Tremor (ET) and Parkinson's Disease (PD). Tremor is a prevalent symptom that significantly impacts physical function and social participation. ET affects approximately 1% of the global population and worsens with age, while PD tremor is often less responsive to conventional dopaminergic therapy. Current treatments, including oral medications (propranolol, primidone), anticholinergics, and deep brain stimulation (DBS), are either limited by efficacy, side effects, or invasiveness. These challenges highlight the need for alternative, less invasive therapeutic options. The rationale for the study is based on the principle of phase-dependent neural modulation. Just as a swing's amplitude can be increased or decreased depending on when it is pushed, neural oscillations underlying tremor can theoretically be suppressed by precisely timed stimulation. Previous studies have shown that TMS over the motor cortex at tremor frequency (\~5 Hz) produces modest improvements in PD rest tremor. This study aims to enhance these effects by targeting amplitude-suppressing phases in the tremor cycle, potentially leading to greater and cumulative tremor reduction. The study has two components: Study 1 (Primary Objective): Determine whether phase-locked TMS can acutely reduce tremor. Participants (20 ET, 20 PD) will undergo two visits where tremor is recorded via inertial measurement units (IMUs) and surface EMG. TMS will be delivered over the motor cortex at or below active motor threshold, synchronized to the participant's tremor phase. The primary outcome is the change in tremor power during stimulation compared to no stimulation, measured objectively via IMU signals. Study 2 (Secondary Objective): Examine whether stimulation at the maximal tremor-suppressing phase, identified in Study 1, produces a larger reduction in tremor amplitude than stimulation at the minimal suppressing phase or sham stimulation. This will involve three additional sessions per participant, randomized for order, with outcomes assessed via IMU tremor power and participant-reported measures including the Quality of Life in Essential Tremor Questionnaire (QUEST), TETRAS, and Unified Parkinson's Disease Rating Scale (UPDRS). Study Design and Procedures: The design is a within-subject crossover. Participants may withhold tremor medications during visits to reduce confounding effects. EMG electrodes and IMU sensors will record tremor, while a figure-of-eight TMS coil will deliver phase-locked pulses. Phase-specific stimulation trains are applied for 3 seconds at intervals, with randomized order across multiple blocks. Study sessions last under two hours, including setup and post-stimulation recordings. Participants are recruited via self-referral or through DeNDRoN, screened for eligibility, and provide informed consent. Inclusion criteria require symptomatic ET or PD tremor, age ≥18, and ability to consent. Exclusion criteria include epilepsy, psychiatric illness, metal implants, pacemakers, or other conditions contraindicating TMS. Participants may withdraw at any time without penalty. Safety Measures: TMS and IMU recordings are low-risk, with potential minor effects including scalp tapping sensations, muscle twitches, or mild headaches, which are managed through monitoring and coil adjustment. Serious adverse events are defined, and procedures for reporting and auditing are established in accordance with UK regulations and Good Clinical Practice. Data Analysis: Tremor power will be quantified from IMU recordings using spectral analysis. Statistical comparisons between stimulation conditions and baseline will be conducted using paired t-tests or Wilcoxon tests. The study will employ validated software for randomization and analysis (SPSS, Matlab). Data will be pseudo-anonymized, securely stored, and archived for long-term research use. Ethical Considerations: The study follows the Declaration of Helsinki, Good Clinical Practice, and institutional approvals. Participants' privacy and data protection are ensured under GDPR standards. There are no commercial conflicts of interest, and participants are reimbursed for travel expenses. In summary, this research aims to evaluate the efficacy of phase-locked TMS as a non-invasive, targeted interventionfor tremor in ET and PD. By systematically stimulating the motor cortex at tremor-specific phases, the study seeks to establish a foundation for future minimally invasive treatments that could complement or replace existing pharmacological and surgical options.
Investigating Subcortical Contributions to Speech Sequencing in Deep Brain Stimulator Recipients
This study will examine how two important brain circuits - one involving the subthalamic nucleus (STN) and one involving the ventral intermediate nucleus of the thalamus (VIM) - contribute to learning and producing speech sequences. Participants will include two groups: 1. individuals with Parkinson's disease who have deep brain stimulation (DBS) devices targeting the STN and 2. individuals with essential tremor who have DBS devices targeting the VIM. Participants will complete speech tasks involving the learning and repetition of novel sound sequences. During some parts of the study, DBS stimulation will be temporarily turned on or off in a controlled research setting. This will allow researchers to examine how stimulation affects both the learning of new speech sequences and the production of previously learned sequences. All STN participants and most VIM participants will also be equipped with a cutting-edge DBS system, the Percept PC, which will enable the recording of deep brain activity during the tasks. The results of this study will improve our understanding of how different brain circuits support speech learning and production. In particular, this study will help to differentiate the roles of the STN and VIM in learning the ordering of speech sounds within a syllable from learning of speech sequences containing multiple syllables. This knowledge may help guide future approaches to optimizing DBS settings to improve both movement and speech outcomes in individuals with neurological disorders, as well as provide greater general insight into how these brain structures contribute to speech production and learning.
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