RECRUITING

Paradoxical Tuberculosis Reactions in Patients Without HIV Infection

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Paradoxical Tuberculosis Reactions in Patients Without HIV Infection

Quick Facts

Study Start:2019-12-20

Study Completion:2029-04-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04052022

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 99 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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). 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).	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.

Inclusion Criteria

Exclusion 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).
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).

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.

Contacts and Locations

Study Contact

Mary E McLaughlin, R.N.

CONTACT

(301) 435-8001

mmclaughli@niaid.nih.gov

Maura M Manion, M.D.

CONTACT

(301) 312-2103

maura.manion@nih.gov

Principal Investigator

Maura M Manion, M.D.

PRINCIPAL_INVESTIGATOR

National Institute of Allergy and Infectious Diseases (NIAID)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Maura M Manion, M.D., PRINCIPAL_INVESTIGATOR, National Institute of Allergy and Infectious Diseases (NIAID)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-12-20

Study Completion Date2029-04-30

Study Record Updates

Study Start Date2019-12-20

Study Completion Date2029-04-30

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Tuberculosis