Feasibility, Safety, and Preliminary Efficacy of Median Nerve Stimulation for Cognitive Dysfunction in Patients With Acute Traumatic Brain Injury (MARS-TBI): Study Protocol for a Pilot Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in global cognitive function assessed by the Mini-Mental State Examination(MMSE)
研究概览
简要总结
Currently, the treatment of cognitive dysfunction after acute TBI remains a challenge, and novel therapeutic methods are urgently needed. Median nerve stimulation (MNS) is a non-invasive neuromodulation technique and recently has shown positive effects in awaking coma of acute brain injury. It has been shown to improve cognition in healthy volunteers and may be a potential therapeutic approach for cognitive dysfunction in patients with acute TBI. Therefore, the main purpose of the study is to evaluate the feasibility, safety, and preliminary efficacy of MNS for cognitive dysfunction in patients with acute TBI.
详细描述
Traumatic brain injury (TBI), a major cause of death and disability, is a significant public health problem in the worldwide. It can cause cognitive dysfunctions including executive function, memory, attention, language and visuospatial function, which seriously affects the patient's quality of life and places a heavy burden on the country and family. Currently, the main therapeutic methods for cognitive impairment include cognitive training, drug therapy, hyperbaric oxygen therapy, and aerobic exercise therapy. They all have been shown to have potentially positive effects on cognitive impairment. However, the improvement in overall cognitive function is inconsistent. Moreover, all the interventions are usually performed during chronic stage of TBI, leading to often delayed and suboptimal therapeutic outcomes. Thus, treatment options for cognitive impairment during the acute stage of TBI remain limited.
Recently, noninvasive neuromodulation techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, transcutaneous auricular vagus nerve stimulation, and median nerve stimulation, were recognized to have promising potentials in improving cognitive function in patients with cognitive impairment caused by stroke, intracerebral hemorrhage, and TBI. Within them, MNS is a simple, inexpensive, and noninvasive neuromodulation technique that has been found to improve recovery from TBI, hasten awakening from coma in our previous study. Furthermore, clinical studies have shown that it can effectively improve cognitive function in healthy individuals and enhance cognitive recovery following stroke. However, whether MNS has the same beneficial effects in those with cognitive dysfunction after TBI is unclear. The investigators designed the present study to assess the feasibility and safety of MNS and the preliminary effects on cognitive dysfunction in patients with acute TBI. The present study details a pilot trial that will be conducted before a large-scale randomized controlled trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Investigator, Outcomes Assessor)
盲法说明
Investigators in charge of the recruitment and follow-up evaluation, outcome assessors, and data analysts will be blinded to group allocation. Participants and independent researchers who apply the MNS will not be blinded. Researchers who monitor patients' safety and perform risk management can access group allocation if necessary. Before the outcome assessment begins at every follow-up evaluation, the participants will be reminded not to reveal any information about their group allocation to decrease the risk of unblinding. If the investigator can detect details of group allocation during follow-up, another blinded researcher will evaluate the outcome.
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18-64 years.
- •Admitted within 3 days post-injury with a Glasgow Coma Scale (GCS) score of 9-12 at admission, accompanied by imaging abnormalities.
- •Presence of cognitive dysfunction assessed within 1-week after injury, with a Mini-Mental State Examination (MMSE) score ≤
- •Pre-injury Clinical Dementia Rating (CDR) score = 0 as reported by family members.
- •With a pre-injury education of ≥6 years, able to comprehend instructions and cooperate in completing scale assessments, magnetic resonance imaging (MRI), and magnetoencephalography (MEG) examinations.
排除标准
- •Requirement for emergent neurosurgical intervention during treatment including surgery, intracranial pressure monitoring device placement, or drainage catheter insertion.
- •Unstable vital signs or hemodynamics, or presence of unstable cardiac, pulmonary, hepatic, renal, or hematopoietic system disorders.
- •Pre-existing central nervous system conditions causing cognitive decline: traumatic brain injury, intracranial infection, brain tumor, epilepsy, stroke, neurodegenerative diseases, carbon monoxide poisoning, and alcohol abuse.
- •Inability to complete assessments or examinations due to severe visual or auditory impairment, severe psychiatric or behavioral disorders, MRI contraindications, and MEG intolerance.
- •Short life expectancy due to critical illnesses.
- •Right forearm with extensive skin lesions or scars, right median nerve injury, brachial plexus injury, cervical spinal cord injury, or intolerance to MNS.
- •Pregnant or lactating women.
- •Participation in other ongoing clinical trials.
研究组 & 干预措施
Median nerve stimulation group
Participants will receive right median nerve stimulation therapy (right median nerve electrical stimulator, XCH-B1, Jiangxi Nuocheng Electrical Equipment Co., Ltd.). Both frequency of 40 Hz and pulse width of 300 µs are fixed and applied within a 20-s on/40-s off protocol. Stimulation will be administered for 8 hours per day over a 2-week period.
干预措施: Median nerve stimulation (Device)
Sham group
The participants in the sham stimulation group will receive no electrical stimulation (0 mA) via an activated stimulator, with all other device settings and procedures identical to those used in the active stimulation group.
干预措施: Sham (Drug)
结局指标
主要结局
Change in global cognitive function assessed by the Mini-Mental State Examination(MMSE)
时间窗: Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.
The MMSE will be used to evaluate global cognitive function. Assessments will be conducted by two trained occupational researchers who are blinded to group allocation and not involved in the intervention.
次要结局
- Global cognitive function (MoCA)(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Verbal fluency(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Language function(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Visuospatial function(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Verbal learning and memory(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Executive function(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Attention and working memory(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Neuropsychiatric symptoms(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Sleep quality(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Anxiety symptoms(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Depressive symptoms(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Apathy(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Agitation(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Level of consciousness(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Functional neurological outcome(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Activities of daily living(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Health-related quality of life(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Functional activities(Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.)
- Neuroimaging outcomes(Baseline (Day 7 after injury) and 1 month after injury.)
- Serum tau level(Baseline (Day 7 after injury) and 1 month after injury.)
- Serum amyloid-β (Aβ) level(Baseline (Day 7 after injury) and 1 month after injury.)
- Serum glial fibrillary acidic protein (GFAP) level(Baseline (Day 7 after injury) and 1 month after injury.)
- Serum S100β level(Baseline (Day 7 after injury) and 1 month after injury.)
- Serum α-synuclein level(Baseline (Day 7 after injury) and 1 month after injury.)