Effects of rTMS With Different Stimulation Spots in Patients With Disorders of Consciousness

Targeting Anterior or Posterior, Where is Better for DOC

Disorders of consciousness are a state in which consciousness is affected by brain damage, resulting in dysfunctions in alertness, awareness, and behavior. Patients with disorders of consciousness can be categorized into coma, unresponsive arousal syndrome（UWS）, and minimally conscious states（MCS）. Common causes include craniocerebral trauma and non-craniocerebral trauma causes such as stroke and ischemic-hypoxic encephalopathy. The number of patients with disorders of consciousness is rapidly increasing worldwide and is not only affecting the lives of individuals and their families, but is becoming a serious public health threat.Transcranial magnetic stimulation uses an electromagnetic pulse to induce focalised neural depolarisation and firing. Repeated transcranial magnetic stimulation, compared with single pulse transcranial magnetic stimulation, can influence brain plasticity and cortical organisation through alterations of neuronal excitability and is now being used to improve consciousness and functional recovery in patients with disorders of consciousness. However, the optimization of TMS stimulation parameters has become one of the key factors affecting the therapeutic efficacy, especially the choice of treatment location.

Method:This study is a randomized double-blind controlled trial.And eighty-four patients are expected to be recruited and they will be randomly assigned in a 1:1:1 ratio to two test groups and one control group of 28 patients each.. Each patient receives a one-week period of repetitive transcranial magnetic stimulation at 10 Hz twice daily for a total of 14 treatments. Primary and secondary evaluation indices will be performed at each baseline and after rTMS treatment. 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 and TMS-EEG will be also recorded to investigate the neurophysiological correlates by rTMS.

Discussion:This study will contribute to the selection of therapeutic target locations for rTMS in patients with disorders of consciousness and has the potential to explore mechanisms of consciousness and to validate the role of rTMS parameter optimization in patients with disorders of consciousness using randomized controlled trials

Study Overview

• Status: Recruiting
• Conditions: Disorder of Consciousness
• Intervention / Treatment: Device: active repetitive transcranial magnetic stimulation; Device: sham repetitive transcranial magnetic stimulation

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ziqin Liao, BSC; Phone Number: 15079991339; Email: ziqinliao1997@163.com
• Study Contact Backup: Name: Qiuyou Xie, PhD; Phone Number: 13903019604; Email: xqy7180@163.com

Study Locations

• China
  • Guangzhou
    • Guangzhou, Guangzhou, China, 510280
      • Recruiting
      • Zhujiang Hospital of Southern Medical University
      • Contact: Ziqin Liao, BSC; Phone Number: 15079991339; Email: ziqinliao1997@163.com
      • Contact: Qiuyou Xie, PhD; Phone Number: 13903019604; Email: xqy7180@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 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 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: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active repetitive transcranial magnetic stimulation on prefrontal lobes; Real stimulation will be delivered on individualized target using a real coil	Device: active repetitive transcranial magnetic stimulation; During the rTMS-active stage, treatment will be given for 7 consecutive days (two 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).
Experimental: Active repetitive transcranial magnetic stimulation on posterior parietal lobes; Real stimulation will be delivered on individualized target using a real coil	Device: active repetitive transcranial magnetic stimulation; During the rTMS-active stage, treatment will be given for 7 consecutive days (two 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).
Sham Comparator: Sham repetitive transcranial magnetic stimulation; Sham stimulation will be delivered on individualized target using a sham coil	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.(train duration: 1s; inter-train interval: 5s; 200 effective stimulation series; 0 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)	The CRS-R includes six items addressing auditory, visual, motor, oromotor, communication, and arousal processes, each with different response categories, and its total score is calculated considering the presence or absence of specific behavioral responses to sensory stimuli, with a range between 0 (worst) and 23 (best). 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.Secondary outcome	immediately after 7 days rTMS session

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline Resting-State EEG	Based on the assumption that specific cortical oscillations indicate varying levels of thalamocortical integrity that has defined four dynamic regimes that build on the mesocircuit model, each detectable with EEG and corresponding to a thalamo cortical state that indicates progressive circuit recovery.These EEG types are labeled A-D (hence, ABCD model) .Later types (C, D) denote more progressive recovery (i.e., are "better") than earlier types, (A, B), which correspond to a quiescent thalamic state.	immediately after 7 days rTMS session
Change from Baseline TMS-EEG	Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) is an effective way to measure cortical activity..In this study, PCIst, a derivative version of PCI, PCIst was chosen as an alternative, which estimates the complexity of TMS perturbations by signal decomposition and recurrence quantification analysis (RQA)	immediately after 7 days rTMS session

Collaborators and Investigators

• Sponsor: Zhujiang Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 30, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: July 25, 2024
• First Submitted That Met QC Criteria: July 25, 2024
• First Posted (Actual): July 30, 2024

Study Record Updates

• Last Update Posted (Actual): July 30, 2024
• Last Update Submitted That Met QC Criteria: July 25, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Consciousness Disorders
• Other Study ID Numbers: L20240725

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