Effects of rTMS With Different Stimulation Spots in Patients With Disorders of Consciousness
NCT Number: NCT06527573
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Disorder of Consciousness
Interventions: DEVICE: active repetitive transcranial magnetic stimulation|DEVICE: sham repetitive transcranial magnetic stimulation
Sponsor: Zhujiang Hospital
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 84
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-07-30
Completion Date: 2026-06-30
Locations: Zhujiang Hospital of Southern Medical University, Guangzhou, Guangzhou, 510280, China

Summary:
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

Primary Outcome Measures: 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: 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