Understanding Paradoxical Reactions in Tuberculosis Treatment

Paradoxical Tuberculosis Reactions in Patients Without HIV Infection

This study is trying to understand why some people without HIV have unexpected reactions while being treated for tuberculosis, by following their progress and collecting samples to find clues.

Quick facts

• Study type: Observational
• Enrollment: 140 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 2 sites (Bethesda, Maryland and 1 other locations)
• Trial ID: NCT04052022 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older diagnosed with confirmed or suspected TB who have been on treatment for at least 2 weeks.

Not a fit: Patients who are not currently undergoing treatment for TB or those with HIV may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to better management and treatment strategies for patients experiencing paradoxical reactions to TB therapy.

How similar studies have performed: While paradoxical reactions in TB have been documented, this study's specific focus on non-HIV patients and its methodology represents a novel approach.

Eligibility criteria

* 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 this trial is running

Bethesda, Maryland and 1 other locations

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)
• Mexican Emerging Infectious Diseases Clinical Research Network (LaRed) — Alcaldia Tlalpan, 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.

Conditions Tuberculosis; Auto-Antibody Production; Host Genetic Predisposition; Immune Reconstitution Inflammatory Syndrome; Biomarkers; Pathogenesis; Natural History