Angioedema Biomarker Research Study

This clinical trial aims to evaluate and compare novel and commercially available diagnostic assays through blood tests for the differential diagnosis and comprehensive assessment of patients experiencing recurrent angioedema attacks, including both urticarial and non-urticarial angioedema. The primary objective is to assess the efficiency of novel diagnostic assays, both individually and in combination, in comparison to currently available commercial tests. The ultimate goal is to establish the feasibility of developing an affordable and accurate laboratory test capable of diagnosing the diverse etiological manifestations of angioedema.

Study Overview

• Status: Not yet recruiting
• Conditions: Angioedema; Urticaria; C1 Inhibitor Deficiency; Angioedemas, Hereditary; Mastocytosis; Indolent Systemic Mastocytosis; Systemic Mastocytoses; ACE Inhibitor-Induced Angioedema
• Intervention / Treatment: Diagnostic test: Venipuncture

Detailed Description

Purpose: The purpose of this prospective non-interventional non-randomized diagnostic study is to first identify patients with recurrent angioedema attacks, then collect their blood samples (venipuncture) and ultimately send the samples to specialized laboratories to perform multiple diagnostic assays, novel and traditional, that can distinguish the various forms of angioedema (urticaria and non-urticarial symptoms and signs), and healthy subjects.

Methods and Materials: Blood specimen collection from a total of 300 patients with recurrent angioedema attacks, and 300 healthy volunteers without a history of angioedema attacks. Laboratory testing will include assays on multiple platforms. Complement testing via immunoassay and biochemistry techniques. Flow Cytometry using multiple markers. Mass Spectrometry that includes bradykinin metabolite and histamine detection. Molecular Genetics include Sanger sequencing, Next Generation Sequencing (NGS), and digital PCR.

Patient population: Study participants to be screened who have a history of recurrent angioedema incidents as well as a population of healthy subjects. A medical history will be documented after obtaining informed patient consent to enter into the clinical trial. Each enrolled participant will have blood collected as whole blood, plasma and serum via venipuncture.

Eligibility criteria (inclusion) for sample collection (angioedema subject):

• Understand and sign the informed consent form before starting any study procedure.
• Adult or Child: aged 12 years of age or older (consent must be signed by a single parent or legal guardian).
• Angioedema symptoms and signs by medical history, or previous laboratory diagnostic testing, or genetically proven cases (e.g. SERPING1 or other mutation). Patients can be on active medication for the treatment and prophylaxis of angioedema. Angioedema cases must be verified by a clinician from IAA.
• Able to perform and endure safely the collection of peripheral blood samples (venipuncture), or optionally agree to have additional testing via a skin punch biopsy.

Eligibility criteria (inclusion) for sample collection (for healthy participant/subject):

• Understand and sign the informed consent form before starting any study procedure.
• Adult or Child: aged 12 years of age or older (consent must be signed by a single parent or legal guardian).
• No history of any angioedema symptoms and signs, previous laboratory diagnostic testing, or genetically proven cases.
• Able to perform and endure safely the collection of peripheral blood samples (venipuncture), or optionally agree to have additional testing via a skin punch biopsy.
• Not on ACE inhibitors and if on blood pressure medication, to indicate the drug(s).

Exclusion Criteria (for all participants):

• Minor: 11 years of age or younger.
• Cannot read or understand the informed consent form and instructions.
• Unable to perform the peripheral blood sample collection.
• Taking medications contraindicated for testing.
• History of excessive bleeding after phlebotomy, e.g. Hemophilia.
• Contraindication due to other health-related issues.

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Henry Li, MD, PhD; Phone Number: 100 877-888-2973; Email: henryli@allergyasthma.us
• Study Contact Backup: Name: Joseph Chiao, MD; Phone Number: 104 8778882973; Email: Jchiao@virantdx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The collection of medical history and peripheral blood (venipuncture) to perform multiple diagnostic assays from patients experiencing recurrent angioedema attacks, including both urticarial and non-urticarial angioedema. Healthy volunteers will not have a medical history of angioedema.

Description

Inclusion Criteria:

• Understand and sign the informed consent form before starting any study procedure.
• Adult or Child: aged 12 years of age or older (consent must be signed by a single parent or legal guardian).
• Angioedema symptoms and signs by medical history, or previous laboratory diagnostic testing, or genetically proven cases (e.g. SERPING1 or other mutation). Patients can be on active medication for the treatment and prophylaxis of angioedema. Angioedema cases must be verified by a clinician from IAA.
• Able to perform and endure safely the collection of peripheral blood samples (venipuncture), or optionally agree to have additional testing via a skin punch biopsy.

Exclusion Criteria:

• Minor: 11 years of age or younger.
• Cannot read or understand the informed consent form and instructions.
• Unable to perform the peripheral blood sample collection.
• Taking medications contraindicated for testing.
• History of excessive bleeding after phlebotomy, e.g. Hemophilia.
• Contraindication due to other health-related issues.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Recurrent Angioedema; Broad definition: Angioedema due to urticaria (histaminergic/mast-cell) or non-urticarial (non-histaminergic) etiology Narrow definition: non-urticarial angioedema - distinguishing between C1-Inhibitor deficiency/dysfunction, and Angioedema with normal levels of C1-Inhibitor.	Diagnostic test: Venipuncture; venipuncture
Healthy Subjects; Broad definition: No medical history of angioedema of any kind, including urticaria (histaminergic) or drug-induced angioedema (e.g. ACE-Inhibitor angioedema)	Diagnostic test: Venipuncture; venipuncture

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Novel versus traditional diagnostic blood test for angioedema	Determining whether novel test methods can be more efficient than currently available or traditional laboratory test for angioedema diagnosis	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic analysis of angioedema versus non-angioedema affected populations	Genetic testing that include know angioedema mutations, such as SERPING1	2 years
Development of novel Bradykinin biomarkers	Mass Spectrometry analysis of plasma for bradykinin metabolites	2 years
Immunoassay laboratory developed tests for angioedema	development of novel immunoassay biomarkers, such as the detection of cleaved HMWK	2 years
Lymphocyte profile studies	Determine whether the immune system has a role in angioedema attacks	2 years

Collaborators and Investigators

• Sponsor: Foundation For Rare Disease Research
• Collaborators: Institute for Asthma & Allergy; Virant Diagnostics, Inc.; MedBio Reference Laboratories, Inc.
• Investigators: Study Director: Lili Wan, PhD, Institute for Asthma & Allergy

Study record dates

Study Major Dates

• Study Start (Estimated): January 15, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: January 8, 2024
• First Submitted That Met QC Criteria: January 8, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: HAE; angioedema; mastocytosis; hereditary angioedema; systemic mastocytosis; indolent systemic mastocytosis; c1-inhibitor deficiency; C1-inhibitor dysfunction; ACE Inhibitor-induced angioedema; serum tryptase
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Neoplasms, Connective Tissue; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Mast Cell Activation Disorders; Angioedema; Angioedemas, Hereditary; Urticaria; Mastocytosis; Mastocytosis, Systemic
• Other Study ID Numbers: Virant-A001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The analyzed data will be published in a peer-reviewed journal and preliminary results published on clinicaltrials.gov website
• IPD Sharing Time Frame: 2 years
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No