Effects of Individualized rTMS in DOC Patients

Effect of Individualized Repetitive Transcranial Magnetic Stimulation (rTMS) in Patients With Disorder of Consciousness

Background: Disorder of consciousness(DOC) is a series of arousal and cognitive disorders secondary to the most severe brain injury. Once a patient is diagnosed with a DOC, a poor prognosis is assumed and the rehabilitation for whom is greatly limited. Therefore, the treatment of DOC poses extraordinary challenges. Various treatments protocols have been reported of successful in promoting rehabilitation of DOC patients. Repetitive transcranial magnetic stimulation(rTMS), as a non-invasive brain stimulation technique, has shown potentials for consciousness rehabilitation of DOC patients as it is effective in regulating the central nervous system.

Methods and design: This protocol is a double-blind randomized sham-controlled crossover trial. Totally 30 participants will be randomly assigned to either group 1 or group 2 in a 1:1 ratio, with 15 patients in each group. Each patient will received 20 sessions, in which 10 sessions will be active and 10 will be sham, separated by 10-days washout period. The active-rTMS will include 10 Hz rTMS over the individual-targeted area on each participants. Primary and secondary evaluating indicators will be performed at each baseline and after rTMS treatment. Primary outcome will be determined as behavioral response to treatment as measured using the Coma Recovery Scale - Revised (CRS-R). Resting-state high-density EEG will be also recorded to investigate the neurophysiological correlates by rTMS.

Discussion:This study will contribute to define the role of rTMS for the treatment of DOC patients and characterise the neural correlates of its action. The investigators proposed a method of individualized target selection for DOC patients based on the existing gold standard CRS-R score and MRI, and used a cross randomized controlled trial to verify the role of rTMS in DOC treatment.

Study Overview

• Status: Recruiting
• Conditions: Transcranial Magnetic Stimulation; Disorder of Consciousness
• Intervention / Treatment: Device: Sham repetitive transcranial magnetic stimulation; Device: individualized repetitive transcranial magnetic stimulation

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chengwei Xu, BSc; Phone Number: +86 134 5045 7096; Email: 943131151@qq.com
• Study Contact Backup: Name: Qiuyou Xie, PhD; Phone Number: +86 139 0301 9604; Email: 764942251@qq.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510280
      • Recruiting
      • Zhujiang Hospital of Southern Medical University
      • Contact: Qiuyou Xie, PhD; Phone Number: +86 139 0301 9604; Email: 764942251@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. acquired brain injuries less than 1 year and more than 28 days in DOC;
2. clinical diagnosis of DOC Disease;
3. no medical history of neuropsychiatric diseases;
4. no contraindications for rTMS or EEG, no sedatives in use or other drugs that might interfere with brain stimulation, such as Na+ or Ca2+ channel blockers or NMDA receptor antagonists;
5. stable state of disease and vital signs;
6. the families of the patients volunteered the patient to participate in the study and provided signed informed consent;
7. the integrity of the individualized stimulation target cortex are verified by MRI.

Exclusion Criteria:

1. patients in other non-invasive or invasive neuroregulation trials;
2. motor evoked potential (MEP) in M1 region cannot be induced by TMS pulse;
3. uncontrolled epilepsy, seizure within 4 weeks before enrollment;
4. metallic implant in the skull, pacemaker, craniotomy under the stimulated site, implanted brain device.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Sham Stimulation Group for Cross Study; Sham stimulation will be delivered on the patients head using a sham coil in the crossover study.	Device: Sham repetitive transcranial magnetic stimulation; The sham coil will be used which has no magnetic field to send to the cerebral cortex while appearing to be the same shape as the active coil, with good approximation of auditory feedback.
Experimental: Individualized rTMS Group for Cross Study; Real stimulation will be delivered on individualized target using a real coil in the crossover study.	Device: individualized repetitive transcranial magnetic stimulation; During the rTMS-active stage, treatment will be given for 10 consecutive sessions (one session daily). The participants will be placed in the semi-reclining position on either a normal chair or a wheelchair and each stimulation session will last 20 minutes with a frequency of 10 Hz (train duration: 1s; inter-train interval: 5s; 200 effective stimulation series; 2000 pulses at 90% of RMT).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline JFK Coma Recovery Scale-Revised(CRS-R) for Crossover Study 1	The Coma Recovery Scale-Revised(CRS-R), a total of 23 points, is widely used to define the level of consciousness and assess neurobehavioral recovery of patients with DOC. It is based on six subscales that assess auditory(4 points), visual(5 points), motor(6 points), motor/speech(3 points), communication(2 points), and arousal processes(3 points). Each item of CRS-R is in good agreement with the diagnostic and differential diagnostic criteria of VS/UWS, MCS and EMCS. The higher scores mean a better outcome.	immediately after 10 days individualized rTMS session
Change from Baseline JFK Coma Recovery Scale-Revised(CRS-R) for Crossover Study 2	The Coma Recovery Scale-Revised(CRS-R), a total of 23 points, is widely used to define the level of consciousness and assess neurobehavioral recovery of patients with DOC. It is based on six subscales that assess auditory(4 points), visual(5 points), motor(6 points), motor/speech(3 points), communication(2 points), and arousal processes(3 points). Each item of CRS-R is in good agreement with the diagnostic and differential diagnostic criteria of VS/UWS, MCS and EMCS. The higher scores mean a better outcome.	immediately after Washout period
Change from Baseline JFK Coma Recovery Scale-Revised(CRS-R) for Crossover Study 3	The Coma Recovery Scale-Revised(CRS-R), a total of 23 points, is widely used to define the level of consciousness and assess neurobehavioral recovery of patients with DOC. It is based on six subscales that assess auditory(4 points), visual(5 points), motor(6 points), motor/speech(3 points), communication(2 points), and arousal processes(3 points). Each item of CRS-R is in good agreement with the diagnostic and differential diagnostic criteria of VS/UWS, MCS and EMCS. The higher scores mean a better outcome.	immediately after 10 days sham rTMS session

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline Resting-State EEG for Crossover Study 1	EEG will be acquired from 66 channels with positions of the International 10-20 System for 10 mins. The relative spectral power (RSP) and functional connectivity (FC) of participants will be calculated by the selected artifact-free EEG epochs at five frequency bands: δ (1-4 Hz), θ (4-8 Hz), α (8-13 Hz), β (13-30 Hz), and γ (30-45 Hz). The investigators will compute off-line analysis to calculate RSP and FC.	immediately after 10 days individualized rTMS session
Change from Baseline Resting-State EEG for Crossover Study 2	EEG will be acquired from 66 channels with positions of the International 10-20 System for 10 mins. The relative spectral power (RSP) and functional connectivity (FC) of participants will be calculated by the selected artifact-free EEG epochs at five frequency bands: δ (1-4 Hz), θ (4-8 Hz), α (8-13 Hz), β (13-30 Hz), and γ (30-45 Hz). The investigators will compute off-line analysis to calculate RSP and FC.	immediately after Washout period
Change from Baseline Resting-State EEG for Crossover Study 3	EEG will be acquired from 66 channels with positions of the International 10-20 System for 10 mins. The relative spectral power (RSP) and functional connectivity (FC) of participants will be calculated by the selected artifact-free EEG epochs at five frequency bands: δ (1-4 Hz), θ (4-8 Hz), α (8-13 Hz), β (13-30 Hz), and γ (30-45 Hz). The investigators will compute off-line analysis to calculate RSP and FC.	immediately after 10 days sham rTMS session

Collaborators and Investigators

• Sponsor: Qiuyou Xie

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: November 26, 2021
• First Submitted That Met QC Criteria: January 10, 2022
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Actual): July 26, 2024
• Last Update Submitted That Met QC Criteria: July 25, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: repetitive transcranial magnetic stimulation; randomized control trial; Disorder of Consciousness
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Consciousness Disorders
• Other Study ID Numbers: L20210505

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No