Paradoxical Reactions in Non Immuno-compromized Patients With Extrapulmonary Tuberculosis

NCT01252992 | Completed

• 2 other identifiers: P0812532010-A00375-34
• Study Type: observational
• Target: 135
• Locations: 1 country
• Sites: 1

Brief Summary

Tuberculous paradoxical reactions (PR) are immune reactions occurring during the course of antituberculous treatment and leading to a worsening of tuberculous symptoms after an initial improvement. This phenomenon has very extensively studied in HIV infected patients where it corresponds to the so called IRIS (immune reconstitution syndrome). However, it laso occurs in non immuno-compromized patients, especially those with extra-pulmonary localization of tuberculosis. The aim of the study is to look for risk factors of paradoxical reaction in non immuno-compromized patients with extra-pulmonary tuberculosis. The investigators will consider clinical, radiological and biological variables, including specific immune and genetic markers. Our secondary goals are to estimate the incidence of PR, describe their natural history; characterize the type of immune response they correspond to, and look for better diagnostic tools.The immunological characterization and the finding of predictive factors of PR, especially the genetic ones will allow a better understanding of biological mechanisms that lead to their occurrence during extra-pulmonary tuberculosis treatment. The establishment of predictive criteria could permit a better surveillance of at risk patients for a rapid treatment, or even a prevention of PR. The establishment of new diagnostic criteria at the time of PR could avoid numerous invasive diagnostic procedures, surgery and/or useless prolongation of antibiotic treatment.

Conditions

Extrapulmonary Tuberculosis

Keywords

Extrapulmonary; Tuberculosis; Paradoxical reaction; Risk factors; Incidence; CT scan; Natural history; Immune system phenomena; Immune markers; Gene Expression Profiling

Outcome Measures

Primary Outcomes (1)

• Risk factors of paradoxical reaction

  Risk factors of paradoxical reaction : clinical, radiological immune and genetic factors

  at 6 months

Secondary Outcomes (3)

• Incidence and natural history of paradoxical reactions

  during the first 6 months

• Immune description of paradoxical reactions

  during the first 6 months

• Preliminary study of Diagnosis factors of paradoxical reaction

  during the first 6 months

Study Arms (2)

1:paradoxical reaction negative (RP-)

control group with tuberculosis but without paradoxical reaction

Genetic: Genetic analysis; Radiation: Body scan (CERVICO THORACO ABDOMINAL) + Cranian IRM; Other: Immunologic analysis

1:paradoxical reaction negative (RP+)

group with tuberculosis and paradoxical reaction

Genetic: Genetic analysis; Radiation: Body scan (CERVICO THORACO ABDOMINAL) + Cranian IRM; Other: Immunologic analysis; Other: QuantiferonTB Gold test

Interventions

Genetic analysis GENETIC

1. identification of candidates genes by a differential analysis of the whole transcriptome of the peripheral leucocytes of 20 PR+ patients and 20 RP- controls, at D0, D15, M2,; 2. Genetic association analysis: comparison of allelic distributions of SNPs (diallelic markers) within the candidate genes, between PR+ and PR- patients, in the whole cohort. One supplementary ACD tube of 5 ml à D0, D15, M2, PR+, for RNA extraction.

1:paradoxical reaction negative (RP+); 1:paradoxical reaction negative (RP-)

Body scan (CERVICO THORACO ABDOMINAL) + Cranian IRM RADIATION

at day 0, Month 2, paradoxical reaction, end of treatment, read by an independent radiologist

1:paradoxical reaction negative (RP+); 1:paradoxical reaction negative (RP-)

Immunologic analysis OTHER

For patients included until 20 PR+ : blood puncture of 4 ACD tubes of 10 ml, 1 EDTA tube of 7,5 ml et 1 heparinate lithium tube of 7,5ml at D0, D15, M2, and M6 and at the time of an potential RP+

1:paradoxical reaction negative (RP+); 1:paradoxical reaction negative (RP-)

QuantiferonTB Gold test OTHER

at M0, M2, M6 and in case of PR+.

1:paradoxical reaction negative (RP+)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Extra-pulmonary tuberculosis

You may qualify if:

• Extrapulmonary tuberculosis, with associated pulmonary localization or not
• Treatment started less than 5 days ago
• Negative HIV serology
• Social insurance
• Age \>= 18- Foreseeable follow-up of at last one year
• Signed Free Inform Consent

You may not qualify if:

• HIV infection
• immuno-suppressive treatment (including corticosteroids \> 10 mg /d prednisone equivalent, however patients with corticotherapy could be included during the phase 2 of the study)
• central neurological system tuberculosis and tuberculous pericarditis - pure pulmonary tuberculosis
• multiresistant tuberculosis
• pregnancy or breast feeding

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Georges Pompidou Hospital

Paris, 75015, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples (immunologic test), DNA, RNA, Biopsy

MeSH Terms

Conditions

Tuberculosis, Extrapulmonary; Tuberculosis

Interventions

Genetic Testing

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Anne BOURGARIT, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2010
• First Posted: December 3, 2010
• Study Start: March 14, 2011
• Primary Completion: February 21, 2018
• Study Completion: February 21, 2018
• Last Updated: May 28, 2021

Record last verified: 2021-05

Locations

FR (1)