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

NCT06314139 | Completed

• 1 other identifier: YanmingXu001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Essential tremor; Transcranial magnetic stimulation; Continuous theta-burst stimulation; RCT

Outcome Measures

Primary Outcomes (1)

• Tremor assessment using Fahn-Tolosa-Marin (FTM) tremor-rating scales

  The primary outcome was tremor assessment using Fahn-Tolosa-Marin tremor-rating scales (FTMTRS). All participants were assessed at baseline, 0 minutes, 10 minutes and 45 minutes post-intervention. Clinical assessment was independently performed by a neurologist specialized in movement disorder, using the Fahn-Tolosa-Marin (FTM) tremor-rating scales which comprises parts A, B and C, to evaluate severity and forms of tremor symptoms. (tremor severity: part A, specific writing/drawing tasks: part B, and functional disability: part C). Each item has 5 levels of scores (0, 1, 2, 3, and 4), representing different degrees of tremor in the patient. The total score of FTMTRS ranges from 0 to 160. The higher the score, the more severe the tremor.

  All participants were assessed at baseline, 0 minutes, 10 minutes and 45 minutes post-intervention.

Secondary Outcomes (2)

• Clinical global impression-improvement (CGI-I) rating scores

  Clinical global impression-improvement (CGI-I) rating scores were assessed approximately 45 minutes after intervention.

• Electrophysiological evaluation of cortical excitability and inhibition measured by TMS.

  Electrophysiological evaluation of cortical excitability and inhibition by transcranial magnetic stimulation (TMS) were assessed at baseline and approximately 45 minutes after intervention.

Study Arms (2)

cTBS group

ACTIVE COMPARATOR

cTBS at 80% action motor threshold (AMT) with 600 pulses over bilateral M1 and cerebellum. 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.

Device: continuous theta-burst stimulation (cTBS)

sham group

SHAM COMPARATOR

Sham stimulation was performed with the same protocol using an inactive coil to mimic true stimulation sound effects, but does not stimulate the brain or produce neurophysiological changes in cerebello-thalamo-cortical (CTC) connections and eyeblink regulation.

Device: continuous theta-burst stimulation (cTBS)

Interventions

continuous theta-burst stimulation (cTBS) DEVICE

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.

cTBS group; sham group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 and over
• Right-hand dominant
• Were willing to participate in the trial and signed informed consent
• Essential tremor Diagnosis based on the International Parkinson and Movement Disorder Society (IPMDS) ET diagnostic criteria in 2017

You may not qualify if:

• A history of trauma 3 months before the onset of the disease, and it can be clearly determined that this history of trauma has led to neurological dysfunction
• Combined with other central nervous system diseases except ET
• drug or alcohol withdrawal-induced tremor, psychogenic/physiological/orthostatic/task-specific tremor
• Contraindications for undergoing cTBS, such as epilepsy history, intracranial metal implants, pacemaker installers, etc
• Skin lesions at stimulation sites
• Pregnant or breastfeeding women

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

Department of Neurology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan Province 610041, P.R. China.

Chengdu, Sichuan, 610041, China

Location

MeSH Terms

Conditions

Essential Tremor

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Xu Yanming

  Department of Neurology, West China Hospital, Sichuan University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: December 5, 2023
• First Posted: March 15, 2024
• Study Start: September 1, 2022
• Primary Completion: April 6, 2023
• Study Completion: June 1, 2023
• Last Updated: March 15, 2024

Record last verified: 2024-03

Locations

CN (1)