Autonomic Nervous System Profile in Hereditary Angioedema (ANS-HAE)

May 7, 2024 updated by: Istituti Clinici Scientifici Maugeri SpA

Hereditary Angioedema Due to C1 Inhibitor Deficiency: Evaluation of the Cardiac Autonomic Nervous System Profile in Patients With and Without Prophylactic Treatment

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)?

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20138
        • Istituti Clinici Scientifici Maugeri

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The group of patients with hereditary angioedema were recruited during a out-patient visit in a tertiary care center. The group of healthy individuals were volunteers recruited from community.

Description

Inclusion Criteria:

  • Age between 18 and 65 years
  • Diagnosis of hereditary angioedema due to C1 inhibitor deficiency (for the group of patients only)

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Patients with hereditary angioedema
Patients with documented diagnosis of hereditary angioedema due to C1 inhibitor deficiency with or without prophylactic treatment and aged between 18 and 65 years.
Healthy individuals
Healthy individuals with an age between 18 and 65 and matched with patients with hereditary angioedema by age and gender.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Short-term heart rate variability
Time Frame: Baseline
Changes in heart rate variability indices analyzed during tilt test
Baseline

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Long-term heart rate variability
Time Frame: Baseline
Changes in heart rate variability indices analyzed during holter ECG recordings
Baseline
Concentration of catecholamines
Time Frame: Baseline
Changes in the concentration of catecholamines, quantified in the blood plasma
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Istituti Clinici Scientifici Maugeri SpA

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 12, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 18, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 18, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 7, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 7, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 10, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 10, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 7, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2746CE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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