Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT06408805 |
| Other study ID # |
2746CE |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 12, 2023 |
| Est. completion date |
March 18, 2024 |
Study information
| Verified date |
May 2024 |
| Source |
Istituti Clinici Scientifici Maugeri SpA |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
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)?
Description:
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.
In this perspective, the identification of markers, like HRV parameters, could play a crucial
role in helping patients and physicians to characterize the ANS control in each patient and
individualize treatment based on the ANS balance.
This study aims to compare the cardiovascular ANS control in healthy subjects and HAE
patients by head-up tilt test monitoring and evaluate the differences in long-term ANS
between healthy controls and HAE patients by Holter ECG monitoring.
