Open Label Study for the Use of Low Intensity Focused Ultrasound for Essential Tremor

Обзор

This open-label pilot study will evaluate the safety, tolerability, feasibility, and preliminary efficacy of repeated low-intensity focused ultrasound pulsation (LIFUP) targeting the ventral intermediate nucleus (Vim) of the thalamus in patients with Essential Tremor (ET). Twelve adults with clinically diagnosed ET will undergo six LIFUP treatment sessions over approximately two weeks using the BrainSonix BX Pulsar 1002 system. Tremor severity will be assessed using clinician-rated scales (TETRAS and FTM), patient-reported quality-of-life measures (QUEST), and objective accelerometry before and after treatment sessions, with additional follow-up visits at one and three months post-treatment. MRI scans will be performed at baseline and after the final treatment session to monitor safety. The study aims to characterize whether non-ablative focused ultrasound can safely and transiently modulate tremor-related thalamic circuits and provide preliminary evidence supporting future controlled trials of LIFUP for ET.

Вмешательства

• Устройство Low Intensity Focused Ultrasound (LIFU)
  Participants will receive low-intensity focused ultrasound pulsation (LIFUP) delivered using the BrainSonix BX Pulsar 1002 investigational device targeting the ventral intermediate nucleus (Vim) of the thalamus.

Первичные конечные точки

• Accelerometric Data of Tremor Severity [Срок оценки: From enrollment until the end of treatment at 2 weeks]

Вторичные конечные точки (2)

• TETRAS [Срок оценки: From enrollment to the end of treatment at 2 weeks.]
• Fahn-Tolosa-Marin Tremor Rating Scale [Срок оценки: From enrollment to the end of treatment at 2 weeks.]

Критерии участия

Критерии включения

• Confirmed clinical diagnosis of ET
• Isolated tremor syndrome, at least 3 years duration
• Subjective complaint of tremor assessed and validated by physician
• Must be willing to comply with the study protocol
• English Proficiency
• At least 18 years of age
• At most 90 years of age

Критерии исключения

• Severe microvascular disease or structural brain lesions equivalent to Fazekas scale of 3 or higher in the periventicular or deep white matter.
• Subjects on blood thinning medications (e.g. Eliquis)
• Recent stroke (within the last 6 months)
• Implanted electrodes (e.g. DBS) in brain
• History of aneurysm
• History of cranial trauma resulting in fracture or traumatic brain injury
• Subjects who are unable to cooperate with the testing.
• Subjects who lack capacity to consent
• Subjects with severe cardiac disease, increased intracranial pressure, or using a transcutaneous electrical nerve stimulation (TENS) unit.
• Severe cardiac disease will be defined as any of the following:

i) History of myocardial infarction within the past 6 months ii) Diagnosis of congestive heart failure with NYHA Class III or IV symptoms iii) History of unstable angina, life-threatening arrhythmias, or use of an implantable cardioverter-defibrillator (ICD) iv) Uncontrolled hypertension (SBP >180 mmHg or DBP >110 mmHg) despite medication v) Any condition judged by the study physician to place the subject at increased risk from study participation

• Subjects with implanted medical devices
• Subjects with a history of seizure disorder.
• Subjects with contraindications to enter MRI environment
• Subjects with a history of substance abuse.
• Subjects who are currently pregnant. This will be verified by a urine test prior to beginning the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• UCLA Semel Institute for Neuroscience and Human Behavior — Los Angeles

Публикации

• Bishay AAED, Swenson AJ, Spivak NM, Schafer S, Bych BP, Gilles SD, Dorobczynski C, Korb AS, Schafer ME, Kuhn TP, Monti MM, Bystritsky A. Preliminary Examination of the Effects of Focused Ultrasound on Living Skin and Temperature at the Skin-Transducer Interface. Bioengineering (Basel). 2024 Nov 8;11(11):1126. doi: 10.3390/bioengineering11111126. PMID 39593786
• Zesiewicz TA, Elble RJ, Louis ED, Gronseth GS, Ondo WG, Dewey RB Jr, Okun MS, Sullivan KL, Weiner WJ. Evidence-based guideline update: treatment of essential tremor: report of the Quality Standards subcommittee of the American Academy of Neurology. Neurology. 2011 Nov 8;77(19):1752-5. doi: 10.1212/WNL.0b013e318236f0fd. Epub 2011 Oct 19. PMID 22013182
• Zeng Q, Guan X, Guo T, Law Yan Lun JCF, Zhou C, Luo X, Shen Z, Huang P, Zhang M, Cheng G. The Ventral Intermediate Nucleus Differently Modulates Subtype-Related Networks in Parkinson's Disease. Front Neurosci. 2019 Mar 11;13:202. doi: 10.3389/fnins.2019.00202. eCollection 2019. PMID 30914916
• Tysnes OB, Storstein A. Epidemiology of Parkinson's disease. J Neural Transm (Vienna). 2017 Aug;124(8):901-905. doi: 10.1007/s00702-017-1686-y. Epub 2017 Feb 1. PMID 28150045
• Stern JM, Spivak NM, Becerra SA, Kuhn TP, Korb AS, Kronemyer D, Khanlou N, Reyes SD, Monti MM, Schnakers C, Walshaw P, Keselman I, Cohen MS, Yong W, Fried I, Jordan SE, Schafer ME, Engel J Jr, Bystritsky A. Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy. Brain Stimul. 2021 Jul-Aug;14(4):1022-1031. doi: 10.1016/j.brs.2021.06.003. Epub 2021 Jun 23. PMID 34198105
• Spivak NM, Korb AS, Reyes SD, Bych BP, Schafer SF, Khanlou N, Johnson EA, Schafer ME, Cohen MS, Kuhn T, Bystritsky A. Histological examination of focused ultrasound effects on human brain tissue. Brain Stimul. 2021 Nov-Dec;14(6):1486-1488. doi: 10.1016/j.brs.2021.09.015. Epub 2021 Oct 1. No abstract available. PMID 34607066
• Spivak NM, Bishay AAED, Haroon J, Hopkins AR, Tanabe J, Halavi S, Hoang-Dang B, Swenson AJ, Schafer SF, Schafer ME, Bystritsky A, Bookheimer SY, Monti MM. Dose-Escalation Study of Amygdalar Transcranial Focused Ultrasound in Healthy Volunteers. medRxiv [Preprint]. 2025 Oct 29:2025.10.21.25338018. doi: 10.1101/2025.10.21.25338018. PMID 41282732
• Shanker V. Essential tremor: diagnosis and management. BMJ. 2019 Aug 5;366:l4485. doi: 10.1136/bmj.l4485. PMID 31383632

Идентификаторы

NCT: NCT07599592 · LIFUP for ET_v8

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗