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CompletedNCT01196702Updated Mar 26, 2024

Lymphocyte Immunophenotyping in Common Variable Immunodeficiency

An observational study in Common Variable Immunodeficiency, Granulomatous Disease and Bronchiectasis, sponsored by Barts & The London NHS Trust. Completed at 1 site in United Kingdom. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-03-26.

Sponsored by Barts & The London NHS Trust · Observational

Study type
Observational
Model
Case-control
Time perspective
Cross-sectional
Enrollment
210
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to discover if differences in the surface markers of B-cells (antibody producing cells of the immune system) in Common Variable Immune Deficiency (CVID) are related to CVID or its complications/treatment (e.g. bronchiectasis, granulomatous disease, immunoglobulin treatment).

The study hypothesis is that the altered B-cell surface markers are related to CVID, and not to the complications or treatment of CVID.

Read the detailed description

Common Variable Immune Deficiency (CVID) is a syndrome containing a spectrum of disorders which results in weakened immunity and recurrent infections. The ESID (European Society for Immunodeficiencies) CVID definition includes patients with marked decrease of IgG (at least 2 standard deviations below the mean for age). Patients must also have disease onset at an age over 2 years, absent isohaemagglutinins and/or response to vaccines and other defined causes of hypogammaglobulinaemia must be excluded. The Euroclass system of classifying CVID is the result of a European multicentre trial attempting to develop a consensus of two existing classification schemes of B-cell immunophenotyping. In this paper it was shown that B-cell immunophenotype correlated with coincidence of clinical sequelae and it suggested implementing this to further classify CVID to give prognostic and therapeutic information. However, it has not yet been shown that these alterations in B-cell immunophenotype are the result of CVID itself and not caused by the treatment or complications of CVID (e.g. immunoglobulin replacement therapy, granulomatous disease, bronchiectasis). The aim of this study is to show that alterations in B-cell immunophenotype are caused by CVID itself and not by its complications or treatment. The study will therefore compare CVID patients to suitable control patients with granulomatous disease, bronchiectasis and on long-term immunoglobulin therapy. A control group of normal people will also be included to ensure the assay can detect normality and to show differences between normal people and patients with CVID.

02

Conditions studied

  • Common Variable Immunodeficiency
  • Granulomatous Disease
  • Bronchiectasis
  • Immunoglobulin Treatment

Keywords

  • common variable immunodeficiency
  • granulomatous disease
  • crohns disease
  • bronchiectasis
  • immunoglobulin replacement or treatment
  • B-cell immunophenotyping
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

Adult patients selected from medical clinics in the order of attendance with common variable immunodeficiency, bronchiectasis, on long-term immunoglobulin treament and granulomatous disease. Must be able to give consent for testing of B-cell immunophenotype. Healthy control samples taken from colleagues.

Inclusion criteria

  • 18 or over
  • Competent to consent
  • Have diagnosis of Common Variable Immunodeficiency, granulomatous disease, on long term immunoglobulin or bronchiectasis.

Exclusion criteria

Exclusion Criteria:

  • Under 18
  • Unable to consent.
  • Medical problem that could alter B-cell immunophenotype (except for the diagnoses in the inclusion criteria)/
04

Study design

Observational model
Case-control
Time perspective
Cross-sectional
Enrollment
210 participants (actual)
Biospecimen retention
Samples with dna

Groups and cohorts

  • CVID

    Patients with common variable immunodeficiency

  • CVID and granulomatous disease

    Patients with CVID complicated with granulomatous inflammation

  • CVID and bronchiectasis

    Patients with CVID complicated by bronchiectasis

  • Control on Immunoglobulin

    Patients on immunoglobulin long-term who do not have an immunodeficiency

  • Control bronchiectasis

    Controls with bronchiectasis not caused by a known immunodeficiency

  • Control with granulomatous disease

    Control patients with Crohn's Disease as this is a disease that causes granulomatous inflammation.

  • Healthy Controls
05

What researchers measure

Primary outcomes

  1. Percentage of B-cells of all lymphocytes

    Look at percentage of cells within the lymphocyte gate that express the B-cell marker CD19, and compare to healthy controls and non-healthy controls.

    Time frame: 5 months

  2. Percentage of class switched memory B-cells as a percentage of B-cells

    Percentage of class-switched memory B-cells (expressing CD27 and CD19), that do not express IgM or IgD, as a percentage of B-cells. This is reduced in CVID and this will be compared between controls and the patients with CVID.

    Time frame: 5 months

Secondary outcomes

  1. Percentage expression of CD21 and CD38

    Look for abnormalities in the CVID group and compare to control groups in the numeber of B-cells expressing low levels of CD21 (CD21 lo), and high CD38.

    Time frame: 5 months

06

Study locations

1 site
  • Barts and the London NHS Trust
    London, E1 1BB, United Kingdom
07

References and documents

Publications

  • Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, Vlkova M, Hernandez M, Detkova D, Bos PR, Poerksen G, von Bernuth H, Baumann U, Goldacker S, Gutenberger S, Schlesier M, Bergeron-van der Cruyssen F, Le Garff M, Debre P, Jacobs R, Jones J, Bateman E, Litzman J, van Hagen PM, Plebani A, Schmidt RE, Thon V, Quinti I, Espanol T, Webster AD, Chapel H, Vihinen M, Oksenhendler E, Peter HH, Warnatz K. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008 Jan 1;111(1):77-85. doi: 10.1182/blood-2007-06-091744. Epub 2007 Sep 26. PubMed 17898316 ↗
08

Registry details

Key details

Study ID
NCT01196702
Lead sponsor
Barts & The London NHS Trust
Responsible party
Mathew Buckland (Consultant Immunologist, Barts & The London NHS Trust) — Principal investigator
First posted
Sep 8, 2010
Start date
Sep 1, 2020
Primary completion
Dec 30, 2023
Completion
Dec 30, 2023
Last update
Mar 26, 2024

Oversight

Data monitoring committee
No
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