Tolerability and Efficacy of Continuous Theta-burst Stimulation for Essential Tremor: A Randomized Study.

Summary

Essential tremor (ET) is one of the most common movement disorders in adults. The prevalence rate among the elderly over 65 years old is about 4.6%. Tremor usually worsens with age, leading to disability and loss of independence, which has an adverse impact on the quality of life of patients. However, the traditional first-line treatment drugs are neither effective enough nor completely safe for ET patients. Although surgical procedures such as deep brain stimulation (DBS) and thalamotomy can be used to better control unilateral limb tremor, many patients are reluctant to choose surgical treatment because it's invasive. Therefore, there is an urgent need to develop new drugs or non-invasive therapies as a better treatment option for ET.

The pathology of the disease is not yet clear, it is generally believed that genetic, aging and environmental factors are related to ET. Hyperactivity of cerebellar function and changes of cerebello-thalamo- cortical (CTC) pathways are currently considered to be the most important pathophysiological mechanisms of ET. Therefore, the cerebellum and cortex may be the best targets for the treatment of tremor.

Continuous theta burst stimulation (cTBS) is one of the non-invasive electrophysiological techniques characterized by plexus stimulation, which is similar to low-frequency repetitive transcranial magnetic stimulation (rTMS) but closer to the physiological state of neural activity, and may inhibit the excitability of the stimulated cortex. The stimulation duration is greatly shortened, which is simpler and easier than the low-frequency rTMS of 20-30 minutes. In addition, functional near infrared spectroscopy (fNIRS) is a new non-invasive functional neuroimaging technique. It mainly uses the difference characteristics of oxyhemoglobin and deoxyhemoglobin in brain tissue for near-infrared light absorption at different wavelengths of 600-900nm. The efficacy, safety, and mechanisms involved in non-invasive stimulation therapy for ET patients are still unclear. There are few studies on the treatment of ET with cTBS, and the sample size is small (the largest sample includes only 23 ET patients). Additionally, there was a lack of exploration on the therapeutic mechanism of cTBS for ET patients. Therefore, the investigators conducted a double-blind, randomized, sham-controlled clinical trial to evaluate the safety and efficacy of cTBS in the treatment of ET patients over both cerebellar and cortical area.

Conditions

• Essential Tremor
• Continuous Theta Burst Stimulation

Interventions

DEVICE

continuous theta-burst stimulation (cTBS)

Continuous theta-burst stimulation (cTBS) was performed with a CCY-I Magnetic Stimulator (YIRUIDE Medical Co., Wuhan, China) with an air-cooled, figure-of-eight 70 mm coil. The site of stimulation during the TMS treatment sessions was bilateral M1 and cerebellum. Real cerebellar cTBS was delivered with the coil positioned over the cerebellar hemisphere, i.e., 3 cm laterally to and 1 cm below the inion. The cTBS protocol uses a complex pattern of stimulation consisting of three-pulse bursts at 50 Hz repeated every 200ms. A total of 600 pulses that lasts for about 40 seconds were applied which could result in a sustained reduction in corticospinal excitability that outlasted the period of stimulation by 45 min. It was delivered at an intensity corresponding to 80 % of the active motor threshold (AMT), this is the minimum stimulation intensity that evokes MEPs of approximately 200 μV in amplitude in tonically contracted muscles.

Sponsors & Collaborators

• West China Hospital

  lead OTHER

Principal Investigators

• Xu Yanming · Department of Neurology, West China Hospital, Sichuan University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-09-01

Primary Completion

2023-04-06

Completion

2023-06-01

Countries

• China

Study Locations