Balance, Sensory Modulation, and Autonomic Response to Different Dosages of Non-invasive Mechanical Vagal Stimulation in Healthy Adults
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 128
- 试验地点
- 2
- 主要终点
- Heart Rate Variability at rest
研究概览
简要总结
The vagus nerve (VN) plays a crucial role in regulating vital functions (heart rate, blood pressure, digestion, and immune response) and maintaining communication between internal organs and the brain. Recent studies have highlighted the therapeutic potential of VN stimulation (VNS) in treating various conditions such as drug-resistant epilepsy, postural control deficit, COVID-19 infection, chronic pain, and intestinal disorders. In addition, there is growing evidence that the molecules released by the VN neurons affect the function of the gut microbiota and that the molecules released by the bacteria in our gut affect the activity of the VN neurons. In particular, Dr. Giacomo Carta (the leader of this study) has shown how painless neck movements, i.e. mechanical VNS (mVNS), can be applied without adverse effects, representing a potential alternative to invasive methods commonly used today. To further investigate the impact of this novel mVNS, this study aims to evaluate the changes induced by three mVNS protocols on physiological parameters such as resting heart rate, and Heart Rate Variability (HRV) at rest, balance in standing, the perceived intensity of mechanical stimuli using the established clinical method of QST (quantitative sensory testing), fecal transit speed, and the molecular composition of stool (for this, stool samples are analyzed). In particular, stool analysis is very relevant for understanding normal digestion. The present research aims to define the optimal intensity of mVNS and to investigate the therapeutic potential of VNS in the treatment of autonomic dysfunction (such as too low or too high heart rate, too low or too fast digestion, throbbing headaches), as well as falls prevention and pain.
详细描述
mechanical VNs in humans, induced by a combination of non-painful physiological neck movements, effectively reduces the HR at rest in humans, without any side effects in the short- and long-term. Indeed, HR reduction is a proxy for the VN increased activity among healthy subjects and patients with systemic diseases or autonomic diseases. Mechanical VNs had been successfully adopted in two clinical trials among chronic pain patients (NCT05345496, NCT05360589), but due to the early stage of these new VNs and the clear advantages of this method, studies refining the stimulation protocol are suitable. Thus, the study aims to investigate the possible dose-dependent effects of mVNs on different physiological parameters in humans. 3 protocols of mVNs will be compared consisting of (1) 4 minutes (2 minutes on each side); (2) 12 minutes (3 sessions of 2 minutes of stimulation, with 2 minutes of rest for each side); (3) 16 minutes (8 minutes on each side). The following outcomes will be assessed before and after the stimulation: HR at rest, HRV, balance on standing, perceived intensity and modulation of mechanical stimuli on the skin of the forehead, and the abdomen, gastrointestinal transit, and a fecal sample from the closest intestinal emptying. A total sample of at least 96 healthy subjects (48 females) aged between 18 and 60 are expected to participate. The bidirectional communication between internal organs and the brain via the VN is a well-established scientific fact. Indeed, VNs has beneficial effects on manifold pathological conditions in humans. However, easy-to-apply, non-invasive, and effective VNs methods and standardized protocols are lacking. The here proposed project aims at refining and critically assessing mVNs methods - a prerequisite for exploring the clinical utility of mVNs and fostering its therapeutic potential given the fundamental role of the VN in regulating health and disease. Results obtained from this project will provide data on mVNs on gut microbiota dynamics and the potential benefits for pain modulation, equilibrium impairments, and gastrointestinal dysfunctions.
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
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •agreement to participate by signing the informed consent form, being 18-60 years old, and sober
排除标准
- •participants having significant neck pain, headache, or leg pain [with Numeric Pain Rating Scale (NPRS) greater than 3/10],
- •pregnancy
- •recent neck or cardiovascular surgery or significant trauma in the preceding 3 months
- •diagnosis of cancer or inflammatory disorders (fever),
- •spinal cord or cauda equina signs,
- •widespread neurological disorders affecting the tone of the limbs and neck muscles
- •underlying diseases, such as diabetes mellitus.
- •pace-maker
- •antibiotic prescription during the last 3 months
- •gastrointestinal surgery,
- •lower extremity injury (acute or overuse) that prevented them from participating in sports activities for at least one day in the previous 6 months.
结局指标
主要结局
Heart Rate Variability at rest
时间窗: The outcome will be measured before the stimulation protocol and immediately after the stimulation protocol
Polar H10 (1000 Hz) Chest Strap (rubber band placed comfortably around the chest above the xiphoid process level) for data acquisition will be worn by the participant for the duration of the assessment and the stimulation protocol. ECG waves will be acquired via Bluetooth to Elite HRV (Version 5.5.9, Asheville, NC, USA) on an Android device. HRV results from Elite HRV displayed on the app will be recorded for analysis with an Open HRV reading 2 minutes before the stimulation and 2 minutes immediately after. At the end of the data acquisition session, the chest strap will be removed. Distance between R peaks in the ECG, defined as RR Interval (Interbeat intervals \[IBIs\]) will be used as a reference to define HRV.
Heart Rate at rest
时间窗: The outcome will be measured before the stimulation protocol and immediately after the stimulation protocol
Heart rate is recorded continuously from 2 minutes before to 2 minutes after the stimulation using a fingertip infrared pulse oximeter. Heart rate will be measured in beats per minute.
Mechanical Pain Intensity
时间窗: The outcome will be measured before the stimulation protocol and immediately after the stimulation protocol
These tests will be adopted to assess peripheral and central sensitization phenomena. Tests will be administered once for each site, using Neuropen with a Neurotip (disposable needle with a defined pressure of 40 g) and by applying 75 g pressure monofilament for 2 seconds on the skin site. If the stimulus is perceived as a pinprick by the participant, it will be requested to rate the pain intensity (NRS, "0 = no pain" to "10 = worst imaginable pain").
次要结局
- One-leg support test(The outcome will be measured before the stimulation protocol and immediately after the stimulation protocol)
- Gut microbiota composition and function(The outcome will be measured before the stimulation protocol and immediately after the stimulation protocol)
- Wind-up ratio(The outcome will be measured before the stimulation protocol and immediately after the stimulation protocol)
- Mechanical pressure intensity(The outcome will be measured before the stimulation protocol and immediately after the stimulation protocol)
- The Bristol Stool Form Scale(The outcome will be measured for 1 week before and for 2 weeks after the administration of e week after the stimulation)
- The Gastrointestinal Symptom Rating Scale(The outcome will be measured before the stimulation protocol, immediately after the stimulation protocol, and one week after the stimulation)
研究者
Giacomo Carta
Postdoc PhD Researcher
University of Vienna