T Cell Interferon-gamma Release Assay (TIGRA) in Immunocompromised Individuals

NCT00707317 | Completed

• 1 other identifier: TBNET-TIGRA
• Study Type: observational
• Target: 1,843
• Locations: 14 countries
• Sites: 21

Brief Summary

Until recently, the tuberculin skin test (TST) was the only available diagnostic assay for detection of latent infection with M. tuberculosis (LTBI). Despite the low overall incidence of symptomatic tuberculosis infection in low-prevalence countries, the potential mortality and morbidity mandate constant vigilance to identify patients at risk for reactivation. Due to systemic immunosuppression, immunocompromised patients with latent M. tuberculosis infection are at increased risk of progression to active disease. This applies to patients with various causes of immunodeficiency such as HIV-infected patients, allogeneic stem cell and solid organ transplant recipients, patients with rheumatoid arthritis and patients with chronic renal failure. Therefore, current guidelines aimed at preventing tuberculosis infection in immunocompromized individuals recommend a generalized screening for evidence of latent infection to target appropriate preventative prophylaxis. At present, tuberculosis control programs exclusively rely on the tuberculin skin test to identify a latent infection in asymptomatic individuals. Recently, novel in vitro assays termed T cell interferon-gamma release assay (TIGRA) have become available that are based on the detection of interferon-gamma (IFN-gamma) production in T cells or supernatants after stimulation with highly specific antigens of M. tuberculosis. Two TIGRA are commercially available, the ELISPOT based T.SPOT.TB and the ELISA based QuantiFERON-TB Gold test (now available as an "IN-TUBE" version). The aim of the study is a prospective comparison of the two commercially available approved TIGRA (QuantiFERON-TB Gold In-Tube and T.SPOT.TB) with the established Mendel-Mantoux skin-test in immunocompromized patients (main focus on sensitivity and specificity). The study hypotheses are as follows:

1. 1.In immunocompromised patients, the two commercially available approved TIGRA (QuantiFERON-TB Gold In-Tube and T.SPOT.TB) have increased sensitivity and specificity as compared to the established Mendel-Mantoux skin-test.
2. 2.Results from QuantiFERON-TB Gold In-Tube and T.SPOT.TB do not differ in immunocompromised patients.

Conditions

Tuberculosis; Monitoring, Immunologic

Keywords

M. tuberculosis; latent tuberculosis infection; Quantiferon assay; ELISPOT assay; tuberculin skin test; immunocompromised patients

Outcome Measures

Primary Outcomes (1)

• IGRA performance

  performance of two IGRAs and skin test in immunocompromised patients

  at the time of analysis

Secondary Outcomes (1)

• active tuberculosis on follow-up

  variable follow-up on all patients

Study Arms (7)

1

HIV infected individuals

2

patients with chronic renal failure

3

patients after solid organ transplantation (lung, liver, kidney, kidney-pancreas)

4

patients with rheumatoid arthritis

5

stem cell transplant recipients

6

immunocompromised patients with confirmed tuberculosis

7

immunocompetent controls with no known risk of exposure or tuberculosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

immunocompetent and immunocompromised patients

You may qualify if:

• Individual as specified for the study population
• Written informed consent
• Indication to perform tuberculin skin test(suspect latent infection, according to standard guidelines, differential diagnosis)

You may not qualify if:

• \<18 years of age

Sponsors & Collaborators

• Tuberculosis Network European Trialsgroup: lead

Study Sites (21)

Cellestis Limited

Carnegie, Australia

Location

National Center of Infectious and Parasitic Diseases

Sofia, Bulgaria

Location

Herlev Hospital

Herlev, Denmark

Location

Research Center Borstel

Borstel, Germany

Location

HIV Treatment and Clinical Research Unit

Frankfurt, Germany

Location

Department of Infectious Diseases, Univ. of Freiburg

Freiburg im Breisgau, Germany

Location

University of the Saarland

Homburg, Germany

Location

Respiratory Medicine, University of Thessaly

Mezourlo-Larissa, Greece

Location

Emerging Bacterial Pathogens Unit

Milan, Italy

Location

National Institute for Infectious Diseases L. Spallanzani

Roma, Italy

Location

WHO Collaborating Center for TB and Lung Diseases

Tradate, Italy

Location

KNCV Tuberculosis Foundation

The Hague, Netherlands

Location

Centro de Diagnóstico Pneumológico

Lisbon, Portugal

Location

Clinica de Pneumologie, Marius Nasta Institute of Pneumology

Bucharest, Romania

Location

Servei de Microbiologia

Barcelona, Spain

Location

Karolinska Institute

Stockholm, Sweden

Location

Centre Antituberculeux, Hôpital Cantonal Universitarie

Geneva, Switzerland

Location

Baþkent Üniversitesi Týp Fakültesi

Ankara, Turkey (Türkiye)

Location

Department of Chest Diseases and Tuberculosis

Ankara, Turkey (Türkiye)

Location

Chest Clinic

London, United Kingdom

Location

Imperial College London

London, United Kingdom

Location

Related Publications (2)

• Sester M, van Leth F, Bruchfeld J, Bumbacea D, Cirillo DM, Dilektasli AG, Dominguez J, Duarte R, Ernst M, Eyuboglu FO, Gerogianni I, Girardi E, Goletti D, Janssens JP, Julander I, Lange B, Latorre I, Losi M, Markova R, Matteelli A, Milburn H, Ravn P, Scholman T, Soccal PM, Straub M, Wagner D, Wolf T, Yalcin A, Lange C; TBNET. Risk assessment of tuberculosis in immunocompromised patients. A TBNET study. Am J Respir Crit Care Med. 2014 Nov 15;190(10):1168-76. doi: 10.1164/rccm.201405-0967OC.

  PMID: 25303140 RESULT

• Lange C, van Leth F, Sester M; TBnet. Viral Load and Risk of Tuberculosis in HIV Infection. J Acquir Immune Defic Syndr. 2016 Feb 1;71(2):e51-3. doi: 10.1097/QAI.0000000000000834. No abstract available.

  PMID: 26761521 RESULT

Related Links

• TBNET website

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma supernatants of stimulated samples for cytokine analysis.

MeSH Terms

Conditions

Tuberculosis; Latent Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Study Officials

• Martina Sester, PhD

  Department of Transplant and Infection Immunology, University of the Saarland, 66421 Homburg

  PRINCIPAL INVESTIGATOR

• Christoph Lange, MD, PhD

  Div. of Clinical Infectious Diseases, Medical Clinic, Research Center Borstel, Germany

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 25, 2008
• First Posted: June 30, 2008
• Study Start: June 1, 2008
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: December 16, 2015

Record last verified: 2015-12

Locations

GR (1); TU (2); AU (1); RO (1); SE (1); DK (1); NL (1); BU (1); CH (1); GB (2); DE (4); IT (3); PT (1); ES (1)