An observational study in Tuberculosis, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Recruiting at 3 sites in 2 countries. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2026-11-02.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Observational
Background:
Most people with tuberculosis (TB) feel better after starting treatment. But for some people, the opposite happens. They may feel better at first, but then suddenly get worse. This is a paradoxical reaction. Researchers want to better understand what causes this reaction and what happens after someone has it.
Objective:
To learn about paradoxical reactions to TB treatment.
Eligibility:
Adults 18 and older diagnosed with confirmed or suspected TB and currently on treatment for at least 2 weeks, with or without signs/symptoms of a paradoxical inflammatory reaction.
Design:
Participants will be screened with a physical exam and medical history. They will give blood and urine samples.
Eligible participants will visit either the NIH Clinical Center or the Mexico Clinic sites 3 times over 6 to 18 months. Each visit will take 7 hours to complete; visits may be scheduled over more than 1 day. Participants may have more visits if their TB symptoms change.
Participants will give blood, urine, and sputum samples. They will have adverse event assessments. They will have 2 to 3 positron emission tomography/computed tomography (PET/CT) scans. PET/CT scans make pictures of the inside of the body. For this, participants will lie on a table that slides into a donut-shaped scanner. They will get a small amount of radioactive dye through an IV, which is a small plastic tube placed in a vein in the arm using a needle.
Participants may have optional apheresis at the NIH site only. For this, blood is taken from a needle in one arm. White blood cells are separated from the rest of the blood. The rest of the blood is returned through a needle in the other arm.
Paradoxical reaction in non-HIV tuberculosis (TB) is a clinical and/or radiologic worsening of a patient s pre-existing TB while receiving anti-TB medications. This phenomenon has been clinically well described for many years and is thought to occur in 10%-25% of HIV-negative patients starting treatment for TB. Paradoxical reactions are diagnosed by excluding other possible causes for worsening of TB signs and symptoms, such as a second infection or treatment failure. However, challenges in culturing TB can complicate early diagnosis of paradoxical reactions.
This is a multisite, international observational study intended to improve understanding of the pathogenesis of paradoxical response to treatment in TB-infected patients who do not have HIV. Each site will follow up to 20 patients with TB who have already initiated or have previously completed treatment and are suspected to have paradoxical reactions, as well as about 40 patients taking TB treatment without signs of paradoxical reactions (controls). All participants will have regular study visits for clinical assessments, blood and sputum collections, positron emission tomography-computed tomography (PET/CT) scans, and optional leukapheresis. Radiography and laboratory evaluations will be performed to identify biomarkers, clinical signs, and molecular explanations for paradoxical reactions. Better understanding of characteristics of paradoxical reactions will assist in earlier diagnosis or even prediction.
1,170 studies on the registry are indexed under Tuberculosis; 175 are open to participants now.
This study's planned enrollment of 140 is below the median of 253 across 317 observational studies indexed under Tuberculosis.
Browse Tuberculosis studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Participants will be recruited from clinics in the surrounding Washington, DC area for the NIH site; and from clinics in Mexico for the foreign site
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Suspected Paradoxical Reaction Group Criteria:
Diagnosed with confirmed (microbiologically or with molecular methods) or suspected (clinical plus or minus histologic diagnosis) TB and currently on ATT for a minimum of 2 weeks, or have completed ATT, with at least 2 of the following signs/symptoms of a paradoxical inflammatory reaction:
Control Group Criteria:
EXCLUSION CRITERIA:
Individuals in either group who meet any of the following criteria will be excluded from study participation:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with TB who have already initiated treatment and are suspected to have paradoxical reactions
Patients with TB who have already initiated treatment without signs of paradoxical reactions (control)
Immunologic and radiographic responses of TB patients with suspected paradoxical reactions.
Characterize immunologic and radiographic responses of TB patients with suspected paradoxical reactions.
Time frame: Throughout study
Biomarkers and/or microbiologic burden correlate with paradoxical TB reactions.
Determine whether biomarkers and/or microbiologic burden correlate with paradoxical TB reactions.
Time frame: Throughout study
Plan to share: No — No plan at this time.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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