Feasibility, Safety, and Preliminary Efficacy of Median Nerve Stimulation for Cognitive Dysfunction in Patients With Acute Traumatic Brain Injury

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство Median nerve stimulation
  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.
• Препарат Sham
  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.

Первичные конечные точки

• Change in global cognitive function assessed by the Mini-Mental State Examination(MMSE) [Срок оценки: Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.]

Вторичные конечные точки (12)

• Global cognitive function (MoCA) [Срок оценки: Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.]
• Verbal fluency [Срок оценки: Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.]
• Language function [Срок оценки: Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.]
• Visuospatial function [Срок оценки: Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.]
• Verbal learning and memory [Срок оценки: Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.]
• Executive function [Срок оценки: Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.]
• Attention and working memory [Срок оценки: Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.]
• Neuropsychiatric symptoms [Срок оценки: Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.]
• Sleep quality [Срок оценки: Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.]
• Anxiety symptoms [Срок оценки: Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.]
• Depressive symptoms [Срок оценки: Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.]
• Apathy [Срок оценки: Baseline (Day 7 after injury), 1 month after injury, and 3 months after injury.]

Критерии участия

Критерии включения

• 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 ≤26.
• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Beijing Tiantan Hospital, Capital Medical University — Пекин

Идентификаторы

NCT: NCT07413562 · HX-B-2024094

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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