Bradykinin-degradating Enzymes Activities in Angiotensin-Converting Enzyme Inhibitors-associated Angioedema

NCT04763577 | Recruiting

• 2 other identifiers: 38RC19.0252020-A00775-34
• Study Type: observational
• Target: 243
• Locations: 1 country
• Sites: 4

Brief Summary

Angiotensin-Converting-Enzyme-inhibitors-dependent angioedema (ACEi-AE) is the most frequent form of bradykinin-mediated AE, with an estimated prevalence of 0.1% to 0.7%. These AE can be explained by the accumulation of bradykinin (BK), a peptide responsible for increase of vascular permeability: ACE inhibitors block ACE, the main inactivation pathway of the BK, thus extending its half-life. In spite of the the stopping of the drug, systematically performed in the case of ACEi-AE, up to 50% of patients relapsed within 6 months, with maximum risk in the first month after stopping. In addition, the discontinuation of these drugs represents a loss of chance for some patients, without clearly established mastocytic (or histaminic) or bradykinic etiology. At present there is no method to predict the risk of crisis recurrence in patients who have developed AE-IEC. The investigators hypothesize that the risk of relapse is associated with a decrease in the activity of BK degradation enzymes (including aminopeptidase P (APP), dipeptidyl peptidase-4 (DPP4), and ECA) that persists at the cessation of IEC.

Conditions

Angio-Oedema Caused by Angiotensin-Converting-Enzyme Inhibitor

Outcome Measures

Primary Outcomes (1)

• Prognostic Value of Bradykinin degradating enzymes

  The primary outcome is to determine the dynamic prognostic value of each of the kinin catabolism enzyme activities, as biomarkers of the risk of relapse at 6 months in patients with BK-AE associated with ACEi.

  Association between the activity of kinin-degrading enzymes (ECA, APP, DPP4) measured by enzyme methods, expressed in tertiles, and relapse at 6 months.

Interventions

Assay of Bradykinin-degradating enzymes. OTHER

Aminopeptidase P activity assay; Dipeptidyl peptidase IV activity assay; Angiotensin Converting Enzyme activity assay; MME gene polymorphisme exploration.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with Angioedema secondary to Angiotensin Converting Enzyme Inhibitors

You may qualify if:

• Men and women at least 18 years old
• Presenting AE secondary to treatment with Angiotensin Conversion Enzyme Inhibitors for less than 15 days, or an isolated AE (without superficial hives), which lasts at least 15 hours, and whose diagnosis is validated by the expert committee,
• Having signed informed and written consent
• And being affiliated with social security

You may not qualify if:

• Patient who had one or more AEs prior to IEC
• Hereditary or acquired deficiency of C1 inhibitor

Sponsors & Collaborators

• University Hospital, Grenoble: lead
• University Hospital, Paris: collaborator
• University Hospital, Rouen: collaborator

Study Sites (4)

Chu Grenoble Alpes

Grenoble, 38043, France

RECRUITING

CHRU de Lille _Hôpital Claude-Huriez

Lille, 59037, France

RECRUITING

AP-HP _St Antoine

Paris, 75571, France

RECRUITING

CHU de Rouen

Rouen, 76 031, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Citrate plasma sample serum sample EDTA sample

Study Officials

• Federica DEFENDI

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Federica DEFENDI, PhD

CONTACT

+33(0)0476765416; fdefendi@chu-grenoble.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2021
• First Posted: February 21, 2021
• Study Start: October 27, 2021
• Primary Completion: October 26, 2025
• Study Completion: October 26, 2025
• Last Updated: February 25, 2025

Record last verified: 2025-02

Locations

FR (4)