Combining Closed-loop Transcutaneous Auricular Vagus Nerve Stimulation and Focal Transcranial Direct Current Stimulation as an Adjuvant Treatment for Acute and Subacute Strokes
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Upper Limb Motor Function Evaluation Using the Wolf Motor Function Test (WMFT)
研究概览
简要总结
Ischemic stroke, the most prevalent neurological disorder, is treated with medication and thrombectomy but with limited success, especially in chronic stages where traditional rehabilitation is the primary option. Stroke often leads to post-stroke autonomic imbalance, deteriorating functional outcomes and increasing recurrence risk. Emerging non-pharmacological treatments like Transcutaneous Auricular Vagus Nerve Stimulation (VNS) and Focused Transcranial Direct Current Stimulation (tDCS) offer new possibilities. VNS targets post-stroke tissue injury and promotes healing and neurogenesis, while tDCS aims to enhance motor learning by rebalancing brain activity. Both therapies seek to improve outcomes in both acute and chronic stroke stages.
详细描述
Ischemic stroke is the most common neurological disease. The main treatment options include medication and endovascular thrombectomy. The benefits of treatments at acute stage are significant but far from satisfactory. There is no effective treatment for improvement at chronic stage, except traditional rehabilitation. In addition, stroke may induce post-stroke autonomic imbalance, further leading to worse post-stroke functional outcomes and the risk of recurrent stroke.
Except for pharmacological therapy against the risk of stroke, non-pharmacological neuromodulation may be proposed as another therapeutic options. Transcutaneous auricular vagus nerve stimulation (VNS) and focused transcranial direct current stimulation (tDCS) may be two of the options. The function of VNS is to modulate post-stroke tissue injury and promote angiogenesis/neurogenesis through non-pharmacological pathway. VNS may increase the parasympathetic activity for balancing the hyper-sympathetic state in the acute stage and enhancing neural plasticity in the chronic stage. On the other hand, the purpose of tDCS is to make substantial motor learning improvements, which may be through the re-balance both excitatory and inhibitory activation between hemispheres after stroke.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years old
- •Subacute ischemic stroke patients within 7-30 days after stroke symptoms is stabilized
- •Stroke will be documented by DWI-MRI
- •Lesion locations at least involve supratentorial area
- •Patients have unilateral weakness documented with manual muscle testing scales less than 4
- •Stable vital signs and stable neurological signs
- •Able to receive regular rehabilitation programs, and 8) modified Rankin Scales (mRS) less than 5.
排除标准
- •A National Institute of Health Stroke Scale (NIHSS) score > 25 at study entry
- •The presence of hemineglect
- •Moderate-to-severe pain in any limb
- •Unstable clinical condition
- •Recurrent strokes or brainstem strokes
- •Marked arrhythmia or cardiovascular complications
- •Bradycardia (HR≤50 bpm) or low blood pressure (SBP≤100 mmHg or DBP≤60mmHg) at admission
- •Patients with radiographic evidence or suspicion of chronic conditions that may predispose them to intracranial hemorrhage including brain arteriovenous malformations, cerebral cavernous malformations, cerebral telangiectasia, multiple previous intracerebral hemorrhages (amyloid angiopathy)
- •Pre-existing coagulopathy, consist of platelet count of ≤100, INR≥ 3, PTT≥ 90
- •Patients suspected of having infective endocarditis and ischemic stroke related to septic emboli
- •Signs or symptoms of acute myocardial infarction, including EKG findings
- •Concomitant experimental therapy
- •Suspected cerebral vasculitis based on medical history and CTA/Magnetic Resonance Angiogram (MRA)
- •Suspected cranial dural arteriovenous fistula, and evidence of dissection in the intracranial cerebral arteries
- •Cerebral venous thrombosis and significant mass effect with midline shift
- •History of left atrial myxoma
- •Presence of contraindication for VNS (TENS) and tDCS: (A) Intracranial space occupied lesion, (B) Presence of a pacemaker, (C) History of brain neurosurgery, (D) Active CNS or systemic infection, (E) Presence of a metallic foreign body implant, (F) Skin abnormalities, (G) History of alcohol/drug abuse, (H) Epilepsy/History of epilepsy at family (I) Hyperacusis, (J) Cognitive/Consciousness disturbance, (K) Pregnancy or nursing females, (L) Use of neuropsycoactive drugs, (M) Psychiatric/ Neurologic disease
- •Not suitable for equipping ECG recorders: (A) Chronic disease, and allergic to polyester, (B) Acute and severe patients
研究组 & 干预措施
tDCS + taVNS
tDCS + taVNS will be applied before rehabilitation.
干预措施: tDCS stimulation (Device)
tDCS + taVNS
tDCS + taVNS will be applied before rehabilitation.
干预措施: taVNS stimulation (Device)
tDCS + sham-taVNS
tDCS + sham-taVNS will be applied before rehabilitation.
干预措施: tDCS stimulation (Device)
tDCS + sham-taVNS
tDCS + sham-taVNS will be applied before rehabilitation.
干预措施: sham taVNS stimulation (Device)
sham-tDCS + taVNS
sham-tDCS + taVNS will be applied before rehabilitation.
干预措施: taVNS stimulation (Device)
sham-tDCS + taVNS
sham-tDCS + taVNS will be applied before rehabilitation.
干预措施: sham tDCS stimulation (Device)
sham-tDCS + sham-taVNS
sham-tDCS + sham-taVNS will be applied before rehabilitation.
干预措施: sham tDCS stimulation (Device)
sham-tDCS + sham-taVNS
sham-tDCS + sham-taVNS will be applied before rehabilitation.
干预措施: sham taVNS stimulation (Device)
结局指标
主要结局
Upper Limb Motor Function Evaluation Using the Wolf Motor Function Test (WMFT)
时间窗: 0, 4, 12 week
* Description: The WMFT is designed to assess motor ability through timed and functional tasks in individuals with upper extremity motor impairment. * Scale Range: Timed Tasks: Seconds to complete, up to 120 seconds per task. Functional Tasks: Scored 0 to 5 on functional ability. * Score Interpretation: Timed Tasks: Lower completion times indicate better motor function. Functional Tasks: Higher scores represent greater functional ability and more normal movement patterns.
Disability Severity Assessment Using the Modified Rankin Scale (mRS)
时间窗: 0, 4, 12 week
* Description: The Modified Rankin Scale (mRS) is a widely used 6-point disability scale evaluating the degree of disability or dependence in daily activities of people who have suffered a stroke. * Scale Range: 0 (no symptoms) to 5 (severe disability). * Score Interpretation: Higher scores indicate a worse outcome, reflecting increased disability.
Motor Function Assessment Using Fugl-Meyer Assessment (FMA) for Upper Extremity (UE) and Lower Extremity (LE)
时间窗: 0, 4, 12 week
* Description: The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index designed to assess motor functioning, balance, sensation, and joint functioning in patients with post-stroke hemiplegia. It evaluates the motor recovery post-stroke, focusing on voluntary movements and joint functions. * Scale Range: Upper Extremity (UE): 0 to 66 Lower Extremity (LE): 0 to 34 * Score Interpretation: Higher scores indicate better motor functioning, reflecting greater voluntary movement capability and reduced impairment.
Mobility and Balance Assessment Using the Time Up and Go Test (TUG)
时间窗: 0, 4, 12 week
* Description: The TUG test measures the time taken by an individual to stand up from a seated position, walk a short distance, turn around, walk back, and sit down. * Scale Range: Time in seconds. * Score Interpretation: Lower times indicate better mobility and balance.
次要结局
- Autonomic Function Assessment through Heart Rate Variability (HRV) Analysis(0, 4, 12 week)
- Quality of Life Evaluation Using the EQ-5D-5L(0, 4, 12 week)
- Cognitive Function Assessment Using Montreal Cognitive Assessment (MoCA)(0, 4, 12 week)
- Depression Severity Measurement Using Montgomery-Asberg Depression Rating Scale (MADRS)(0, 4, 12 week)