Undetectable IgE as a Sentinel Biomarker for Humoral Immunodeficiency

• ClinicalTrials.gov Identifier: NCT03968211
• Recruitment Status: Completed
• First Posted: May 30, 2019
• Last Update Posted: March 29, 2024
• Sponsor: University of Virginia
• Collaborators: CSL Behring; Jeffrey Modell Foundation
• Information provided by (Responsible Party): Larry Borish, MD, University of Virginia

Study Description

Brief Summary:

This study is trying to find out if an undetectable serum immunoglobulin E (IgE) is a biomarker, or early sign of, the development of immune deficiency.

Condition or disease	Intervention/treatment	Phase
Immune Deficiency	Biological: Salmonella typhi polysaccharide vaccine	Phase 1

Detailed Description:

IgE is the antibody thought to be responsible for developing allergies. Undetectable serum IgE (an IgE below the lower limit of detection) is found in about 3% of the general population. In the past, it has been thought that having an undetectable IgE does not have any health impact, other than meaning that you are at low risk for having allergies. However, recent studies of patients with undetectable IgE have shown higher rates of infections, autoimmune disease and cancer.

Patients with an immune deficiency called common variable immunodeficiency (CVID) also have higher rates of infections, autoimmune disease and cancer. Recently, we have shown that most patients with CVID have a low/undetectable serum IgE.

This study is trying to find out if an undetectable serum IgE is a biomarker, or early sign of, the development of CVID or other antibody deficiencies

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Undetectable IgE as a Sentinel Biomarker for Humoral Immunodeficiency
• Actual Study Start Date: July 1, 2019
• Actual Primary Completion Date: December 31, 2023
• Actual Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vaccine; Subjects who meet enrollment criteria will be administered a single intramuscular dose of the Salmonella typhi polysaccharide vaccine	Biological: Salmonella typhi polysaccharide vaccine; Salmonella typhi polysaccharide vaccine; Other Name: Typhim Vi

Outcome Measures

Primary Outcome Measures :

1. Vaccination response [ Time Frame: 4-6 weeks ]
   IgG to Salmonella typhi will be measured, with a normal response calculated as at least a 2-fold increase in IgG titers post-vaccination

Secondary Outcome Measures :

1. Epsilon germline transcript production [ Time Frame: 3 days ]
   B cells isolated from subjects will be evaluated to determine their ability to produce Epsilon germline transcript in response to stimulation

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Age 18-80
• Willingness and ability to comply with scheduled visits and study procedures
• Undetectable serum IgE (defined as >2 IU/mL or the lower threshold of detection)
• Normal or high serum immunoglobulins (within or above laboratory reference range for IgG, IgA, and IgM)
• patients previously seen at the University of Virginia Asthma, Allergy, and Immunology clinics where undetectable serum IgE was noted
• Control subjects must have participated in study IRB#14457 (only applicable for healthy controls in epsilon germline transcript portion of the study)

Exclusion Criteria:

• The following vulnerable populations will be excluded: pregnant women, fetuses, neonates, children, prisoners, cognitively impaired, educational or economically disadvantaged, non-English speaking subjects
• Known personal history of immunodeficiency
• Known personal history of recurrent infections
• Low serum immunoglobulins (below the laboratory reference range for IgG, IgA, or IgM)
• Recent or current treatment with systemic immunosuppression within the past 30 days

Contacts and Locations

Locations

United States, Virginia

University of Virginia Health System

Charlottesville, Virginia, United States, 22908

Sponsors and Collaborators

University of Virginia

CSL Behring

Jeffrey Modell Foundation

Investigators

• Principal Investigator: Larry Borish, MD; University of Virginia

  Study Documents (Full-Text)

Documents provided by Larry Borish, MD, University of Virginia:

Informed Consent Form  [PDF] May 24, 2019

More Information

Publications:

Lawrence MG, Palacios-Kibler TV, Workman LJ, Schuyler AJ, Steinke JW, Payne SC, McGowan EC, Patrie J, Fuleihan RL, Sullivan KE, Lugar PL, Hernandez CL, Beakes DE, Verbsky JW, Platts-Mills TAE, Cunningham-Rundles C, Routes JM, Borish L. Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID). J Clin Immunol. 2018 Apr;38(3):225-233. doi: 10.1007/s10875-018-0476-0. Epub 2018 Feb 17.

• Responsible Party: Larry Borish, MD, Professor of Medicine and Microbiology, University of Virginia
• ClinicalTrials.gov Identifier: NCT03968211
• Other Study ID Numbers: 21453
• First Posted: May 30, 2019
• Last Update Posted: March 29, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified IPD that underlie results in a publication will be made available upon request of another researcher or if required by the publisher
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Starting 6 months after publication

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Larry Borish, MD, University of Virginia:

immunodeficiency; IgE

Additional relevant MeSH terms:

Immunologic Deficiency Syndromes; Immune System Diseases