Understanding Paradoxical Reactions in Tuberculosis Treatment

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This observational study aims to investigate paradoxical reactions in patients undergoing treatment for tuberculosis (TB) who do not have HIV. Researchers will follow up to 60 participants, including those experiencing paradoxical reactions and those without, to collect clinical data, blood, urine, and sputum samples. Participants will undergo regular assessments and imaging to identify biomarkers and understand the underlying mechanisms of these reactions. The study seeks to improve early diagnosis and prediction of paradoxical responses in TB treatment.

Why it matters

Who can join: the full rules

* INCLUSION CRITERIA:

Suspected Paradoxical Reaction Group Criteria:

1. Aged greater than or equal to 18 years.
2. 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:

   * Recrudescent symptoms of TB after initial clinical improvement.
   * Change in physical exam after initial clinical improvement suggestive of new inflammatory process (e.g., lymphadenopathy or new findings on pulmonary exam).
   * Worsening radiographic evidence of disease after initiation of treatment, as compared with imaging prior to or earlier in treatment.
   * Laboratory evidence of acute inflammatory response, including the development of leukocytosis (white blood cell count \> 10,000 cells/microL) or a change of C-reactive protein (CRP) \> 5 mg/L compared to prior laboratory values.
   * Worsened organ function after initial clinical improvement.
3. The above sign/symptom(s) cannot be explained by a newly acquired infection, clinical course of a previously recognized infectious agent, side effects of the ATT, the presence of drug resistance, or any other condition except for paradoxical reaction.
4. Willingness to allow storage of blood or tissue samples for future research.
5. Ability of participant to understand study requirements and give informed consent.
6. Has a primary care physician and is being followed by the local Department of Health for their TB (or has plans to arrange after enrollment if enrolled early in course from inpatient transfer).

Control Group Criteria:

1. Aged greater than or equal to 18 years.
2. Diagnosed with confirmed (microbiologically or with molecular methods) or suspected (clinical plus or minus histologic diagnosis) TB.
3. Presenting 2 to 4 months after starting ATT to match timing of paradoxical reactions.
4. Willingness to allow storage of blood or tissue samples for future research.
5. Ability of participant to understand study requirements and give informed consent.
6. Has a primary care physician and is being followed by the Department of Health for their TB (or has plans to arrange after enrollment if enrolled early in course from inpatient transfer).

EXCLUSION CRITERIA:

Individuals in either group who meet any of the following criteria will be excluded from study participation:

1. HIV infection. (Individuals with HIV infection may be eligible for a separate study exclusively evaluating persons living with HIV.)
2. Pregnant or breastfeeding.
3. Uncontrolled psychiatric disease, substance use, or inappropriate conduct unsuitable for a research study.
4. Malignancy requiring imminent or ongoing treatment including radiation, chemotherapy, or immunotherapy.
5. Debilitating or chronic conditions that would limit ability to participate in the study.
6. Emergent or urgent clinical conditions not due to studied disease of interest requiring immediate treatment that would be unsuitable for a research study. These patients would be transferred to an emergency room and able to rescreen when condition has been stabilized.

Where it's running

• National Institutes of Health Clinical Center
  Bethesda, Maryland, United States Recruiting
• Mexican Emerging Infectious Diseases Clinical Research Network (LaRed) INCMNSZ
  Mexico City, Mexico Recruiting
• Mexican Emerging Infectious Diseases Clinical Research Network (LaRed) INER
  Mexico City, Mexico Recruiting

Study contacts

• Principal investigator: Maura M Manion, M.D. — National Institute of Allergy and Infectious Diseases (NIAID)
• Study coordinator: Mary E McLaughlin, R.N.
• Email: mmclaughli@niaid.nih.gov
• Phone: (301) 435-8001

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.