Clinical trial NCT00904956: Study of Latent Tuberculosis Infection (LTBI) by High Resolution Scanner
Official title: Study of Latent Tuberculosis Infection (LTBI) by High Resolution Scanner
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Tuberculosis
Keywords: Latent Tuberculosis Infection
High Resolution Scanners
Dynamic Hypothesis of Latent Tuberculosis Infection
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
Collaborators: name: CIBERES CRP-TB program
First posted: 2009-05-20
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Only a single population is going to be studied: the LTBI, thus people with proof to be M. tuberculosis infected but demonstrating not having active disease.

As the first approach to demonstrate the Dynamic Hypothesis in humans, up to 6 people will be included as controls.

Brief summary: It is traditionally considered that someone with a positive tuberculin skin test (TST) (and/or positive result in Cell Interferon-Gamma Release Assay (TIGRA), depending on the different countries' guidelines) is infected but not ill when the absence of lesions is demonstrated in a thorax X-Ray assay. Even though, the experiences described in literature using cows and pigs as animal models for the study of LTBI demonstrate the presence of this kind of lesion in the animals, even too small to be detected by X-Ray assay, which would suggest they also could happen in human LTBI. Nowadays, the High Resolution Scanners (HR TC) offer the possibility of detecting any lesion approximately 1 mm in diameter, so the investigators plan to use this technique to screen people already infected by M. tuberculosis (but not ill, following the Diagnosis Standard Guidelines).

Additional pathological analysis of resected and post-mortem tissues will provide lesion-based profiles of humans infected with tuberculosis.

Detailed description: It is traditionally considered that the development of LTBI is due to the M. tuberculosis ability to develop a dormancy state within well-structured lesions (granulomas), which can remain in the lung of the host even for life. The investigators have developed a new original hypothesis based on scientific evidence that takes into account the idea that a lesion cannot be held forever, because the host tends to remove any lesion in order to rebuild the original parenchyma, in a healing process. Even if M. tuberculosis can remain in a dormant/non-replicating state for a long period, this is an important but not sufficient factor to explain the LTBI. The Dynamic Hypothesis tries to explain the existence of LTBI in spite of the healing process that could remove it by a constant reinfection of the host's tissue.

Eligibility criteria: Inclusion Criteria:

* People with TST+ (plus positive TIGRA result, if possible) and normal thorax X-ray assay (normal as absence of any detectable lesion)

Exclusion Criteria:

* Active TB
* Any medical condition or illness that could compromise the volunteer's health if entering the project

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Fundació Institut Germans Trias i Pujol
state: Barcelona
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Barcelona
country: Spain
facility: Teknon Foundation
Study officials:
affiliation: Fundació Institut Germans Trias i Pujol
name: Pere-Joan Cardona, MD, PhD
role: STUDY_DIRECTOR
affiliation: Fundació Institut Germans Trias i Pujol
name: Cristina Vilaplana, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cardona PJ. A dynamic reinfection hypothesis of latent tuberculosis infection. Infection. 2009 Apr;37(2):80-6. doi: 10.1007/s15010-008-8087-y. Epub 2009 Mar 23.
citation: Caceres N, Tapia G, Ojanguren I, Altare F, Gil O, Pinto S, Vilaplana C, Cardona PJ. Evolution of foamy macrophages in the pulmonary granulomas of experimental tuberculosis models. Tuberculosis (Edinb). 2009 Mar;89(2):175-82. doi: 10.1016/j.tube.2008.11.001. Epub 2008 Dec 24.
citation: Cardona PJ. New insights on the nature of latent tuberculosis infection and its treatment. Inflamm Allergy Drug Targets. 2007 Mar;6(1):27-39. doi: 10.2174/187152807780077282.
citation: Mack U, Migliori GB, Sester M, Rieder HL, Ehlers S, Goletti D, Bossink A, Magdorf K, Holscher C, Kampmann B, Arend SM, Detjen A, Bothamley G, Zellweger JP, Milburn H, Diel R, Ravn P, Cobelens F, Cardona PJ, Kan B, Solovic I, Duarte R, Cirillo DM; C. Lange; TBNET. LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement. Eur Respir J. 2009 May;33(5):956-73. doi: 10.1183/09031936.00120908.
citation: Gil O, Diaz I, Vilaplana C, Tapia G, Diaz J, Fort M, Caceres N, Pinto S, Cayla J, Corner L, Domingo M, Cardona PJ. Granuloma encapsulation is a key factor for containing tuberculosis infection in minipigs. PLoS One. 2010 Apr 6;5(4):e10030. doi: 10.1371/journal.pone.0010030.
citation: Cardona PJ. Revisiting the natural history of tuberculosis. The inclusion of constant reinfection, host tolerance, and damage-response frameworks leads to a better understanding of latent infection and its evolution towards active disease. Arch Immunol Ther Exp (Warsz). 2010 Feb;58(1):7-14. doi: 10.1007/s00005-009-0062-5. Epub 2010 Jan 5.