Hereditary Angioedema Due to C1 Inhibitor Deficiency: Evaluation of the Cardiac Autonomic Nervous System Profile in Patients With and Without Prophylactic Treatment
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Short-term heart rate variability
研究概览
简要总结
The goal of this study is to compare the autonomic nervous system control of patients with hereditary angioedema to healthy individuals.
The main questions it aims to answer are:
Are there differences in the autonomic nervous system control between patients with hereditary angioedema and healthy individuals during short-term resting period and during orthostatic challenges?
Are there differences in the autonomic nervous system control recorded over long-term periods (i.e. 24 hours)?
详细描述
Angioedema (AE) without wheals is a localized self-limiting edema associated with different mechanisms. The best-known form is hereditary angioedema (HAE) due to C1 inhibitor deficiency (C1-INH), a rare disease with a prevalence of 1:65000 in Italy. Symptoms include swelling of the extremities, genitals, bowel mucosa, face, and upper airway including the larynx. Laryngeal attacks, if not treated, can lead to death. AE attacks are unpredictable and occur episodically upon release of the main mediator of the attack, namely bradykinin, resulting from hyperactivation of the contact system lacking its main control protein C1-INH.
The overall result is an impairment of the endothelial function associated with increased vascular permeability. The release of bradykinin occurs locally, in an unpredictable way, at times facilitated by trauma and different triggers such as stress.
In C1-INH-HAE patients, the autonomic nervous system (ANS) has a role in the regulation of vascular permeability, for example via the baroreflex mechanism. It is also known that sympathetic nervous system inhibition by the α2 agonist clonidine reduces microvascular permeability in endotoxemic animals, suggesting that antagonizing the sympathetic nervous system might prove beneficial in stabilizing capillary leakage during inflammation. Similarly, the vagus nerve has a protective role in models of inflammation such as ischemia-reperfusion injury. The parasympathetic tone, acting on the B2-receptors in the nucleus ambiguous, can also be modulated by bradykinin. The ANS could be investigated using the tilt test and Holter ECG monitoring in current clinical practice when its impairment is suspected. Power spectral analysis of heart rate variability (HRV), i.e. the analysis of the spontaneous fluctuations of the heart period, is exploited to analyze data collected during the tilt test and Holter-ECG, deriving indices of the autonomic control.
In C1-INH-HAE patients the cardiac ANS was investigated during a remission period, during the AE attack and its prodromal phase.
It has been demonstrated that HRV analysis, extended to multiday ECG recordings, may furnish an early marker of an angioedema attack.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age between 18 and 65 years
- •Diagnosis of hereditary angioedema due to C1 inhibitor deficiency (for the group of patients only)
排除标准
- •Any type of chronic diseases requiring chronic treatment.
- •Active acute disease
- •Sars-Cov2 infection in the previous three months
- •Acute attacks experiences within the previous week and within 72 hours after the enrollment
- •Patients in prophylaxis treated off-label.
结局指标
主要结局
Short-term heart rate variability
时间窗: Baseline
Changes in heart rate variability indices analyzed during tilt test
次要结局
- Concentration of catecholamines(Baseline)
- Long-term heart rate variability(Baseline)