Immune Responses to Mycobacterium Tuberculosis (Mtb) in People With Latent Tuberculosis Infection With or Without Concomitant Helminth Infection

NCT02225158 | Terminated

• 2 other identifiers: 14017814-I-0178
• Study Type: observational
• Target: 1
• Locations: 1 country
• Sites: 2

Brief Summary

Background: Tuberculosis (TB) is a severe disease and a major cause of death in many people worldwide. It is caused by a bacteria that enters through the lungs and can spread elsewhere in the body. People with latent TB have the bacteria that lie dormant but can become active and cause disease. These people are offered treatment to prevent development of active TB. Worldwide, a lot of people with LTBI also have a parasitic worm called a helminth that can stay in the gut or the blood. These parasites can affect the immune system and cause diseases like TB to become worse. Researchers want to see how helminth infection makes it harder for people to fight TB infection. Objectives: \- To study how the immune system of people with latent tuberculosis infection (LTBI) acts to prevent development of active TB. Also, to study how helminth infection might affect this immune response. Eligibility:

• Adults age 18 70 with LTBI as defined by an approved blood test called QuantiFERON TB Gold.
• No evidence of infections like Hepatitis or HIV
• Pregnant subjects and subjects taking medications that suppress the immune system are not eligible.
• Have not received prior treatment for LTBI. Participants might be still eligible if prior treatment for active TB has been received Design: Screening phase: \- Participants will be screened with medical history, physical exam, and blood tests for other infections/conditions which might affect the immune system. They will have testing for active TB i.e. blood testing as well as testing of their spit, scans and X-rays. Baseline phase:
• Only eligible participants will be entered into the study.
• Participants will have interviews, medical history, and physical exam.
• Blood will be drawn from an arm vein for testing.
• Participants will collect stool samples at home for 3 days in a row to test for helminth infection..
• Participants may have apheresis. Blood cells are removed by needle. They pass through a separator machine which returns everything but the cells back to the participant.
• Participants may have procedures at the start and end of the study that let researchers look into the lungs and collect cells. Study phase, about 2 years:
• All participants will be offered treatment for LTBI which lasts 6-9 months.
• Participants being treated for LTBI will have about 11 study visits. They will visit monthly for 9 months while on treatment, then 6 and 12 months after treatment.
• Participants not eligible/refusing treatment for LTBI will be made aware of active TB, then have 3 other visits, about 6, 12, and 24 months after the baseline visit.
• Participants who have helminth infection will receive appropriate treatment.
• All participants will have blood drawn at each visit.

Conditions

Latent Tuberculosis Infection

Keywords

Immunity; Co-Infection; Parasite; Mycobacteria

Outcome Measures

Primary Outcomes (1)

• Define the immunologic differences in CD4+ T cell responses between helminth-infected and uninfected subjects with concomitant latent TB at the time of diagnosis and on serial follow-up.

  Pre Treatment for LTBI and pre defined post treatment time points

Secondary Outcomes (2)

• Evaluate the immune phenotype and functionality of tissue resident immune cells obtained by bronchoalveolar lavage in subjects with LTBI and either: 1) structural lung damage from prior treated/healed pulmonary tuberculosis or 2) recent prolonge...

  Pre Treatment for LTBI and pre defined post treatment time points LTBI and pre definedpost treatment timepoints

• Define the role of stable long lasting antigen-specific IL-2 producing CD4+ central memory T cells in identifying subsets of patients with LTBI

  Pre Treatment for LTBI and pre defined post treatment time points LTBI and pre defined post treatment timepointspoints

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must meet the following criteria:
• Subjects must have 1 of the following:
• Untreated LTBI, defined as positive Quantiferon TB Gold assay; absence of active TB disease as determined by history, physical examination, chest X-ray, and negative sputum smear and culture for Mtb; and no history of prior treatment for LTBI. OR
• Chronic inactive TB, defined as past history of documented or selfreported active pulmonary TB for which treatment was received; current negative sputum smear and culture for Mtb; and a positive result on the Quantiferon TB Gold assay. These subjects will compose the treatment-induced LTBI group and will not require treatment for LTBI.
• Age 18-70 years. Subjects over the age of 70 will not be included due to the increased potential for immune senescence
• With or without clinical/microbiologic/serologic evidence of untreated concurrent helminth infection
• Agree to have blood specimens stored for future studies
• Subjects must have 1 of the following:
• Documented or self reported history of prior treated TB with positive Quantiferon TB Gold test and structural lung findings of chronic inactive tuberculosis on radiologic imaging, defined as: a) calcified Ghon focus with or without apical calcified nodules (Simon foci), b) parenchymal or pleural calcification, and/or c) apical fibrosis and cavitary changes. OR
• History of recent prolonged (greater than or equal to 3 months) exposure to a confirmed case of active TB disease.
• Able and willing to arrange to have another person drive them home after the procedure
• Able and willing not to eat or drink anything for 6 hours prior and 2 hours after the procedure
• Agree to have respiratory tract samples stored for future research

You may not qualify if:

• A subject will be excluded if they meet any of the following criteria:
• Presence of active TB disease
• Treatment for helminth infection within the past year
• Positive at screening for HIV, hepatitis B, and/or hepatitis C Cardiovascular instability (Blood pressure: Systolic \>180 or \<90 mm/Hg or Diastolic \>100 or \< 50 mm/Hg; pulse \<40 or \>110)
• Inadequate peripheral venous access
• Anemia (hemoglobin \<11 g/dL)
• Current use of corticosteroids or other immunosuppressive agents or documented diagnosis of a primary immunodeficiency disorder
• Underlying heart disease, lung disease, bleeding disorder, or other conditions that, in the judgment of the investigator, contraindicates apheresis
• Temperature greater than or equal to 38.5 degrees C or other clinical evidence of an acute infection at screening
• Currently pregnant or breastfeeding
• History of recent/acute clinically significant pulmonary compromise. This will be defined by the following criteria:
• New lung infection or change in status of chronic lung infection or significant new findings on chest X-ray or CT scan
• Asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past two years, or that required the use of oral or parenteral corticosteroids during the past two years
• Clinically significant reactive airway disease that does not respond to bronchodilators
• Unstable chronic lung disease such as Chronic Obstructive Pulmonary Disease (COPD) or pulmonary fibrosis

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Montgomery County Public Health Services, TB, Refugee and Migrant Health

Silver Spring, Maryland, 20902, United States

Location

Related Publications (3)

• Elias D, Akuffo H, Pawlowski A, Haile M, Schon T, Britton S. Schistosoma mansoni infection reduces the protective efficacy of BCG vaccination against virulent Mycobacterium tuberculosis. Vaccine. 2005 Feb 3;23(11):1326-34. doi: 10.1016/j.vaccine.2004.09.038.

  PMID: 15661380 BACKGROUND

• Flynn JL, Chan J. Immunology of tuberculosis. Annu Rev Immunol. 2001;19:93-129. doi: 10.1146/annurev.immunol.19.1.93.

  PMID: 11244032 BACKGROUND

• Ewer K, Millington KA, Deeks JJ, Alvarez L, Bryant G, Lalvani A. Dynamic antigen-specific T-cell responses after point-source exposure to Mycobacterium tuberculosis. Am J Respir Crit Care Med. 2006 Oct 1;174(7):831-9. doi: 10.1164/rccm.200511-1783OC. Epub 2006 Jun 23.

  PMID: 16799072 BACKGROUND

MeSH Terms

Conditions

Latent Tuberculosis; Coinfection; Mycobacterium Infections

Condition Hierarchy (Ancestors)

Tuberculosis; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Study Officials

• Thomas B Nutman, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 23, 2014
• First Posted: August 26, 2014
• Study Start: August 15, 2014
• Primary Completion: May 11, 2017
• Study Completion: May 11, 2017
• Last Updated: July 2, 2017

Record last verified: 2017-05-11

Locations

US (2)