Latent TuberculosisNCT01571739
Determining Risk in Latent Tuberculosis
An observational study of Latent Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in South Korea.
Trial summary
Background: Tuberculosis (TB) is a leading cause of death worldwide. Those who are exposed to the TB bacteria but have not become sick are said to have latent TB. Many people with latent TB will not get sick from it, but some people will develop active TB and become sick. Read more about this study
- Who is it for?
- Ages 20 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Latent Tuberculosis
- How many people
- 18 participants
- Where
- 1 siteSouth Korea
- Study dates
- 2 Jan 2012to 20 May 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Either confirmed sputum smear positive and culture positive for M. tb within the last 12 months OR sputum smear positive and genotypically confirmed M.tb with culture awaited
- Age greater than or equal to 20 years old
- 20 Smear Positive Pulmonary TB Biomarker Index Case Controls:
- Genotypically confirmed sputum smear positive pulmonary tuberculosis
- Culture awaited or confirmed Mtb
- Not commenced anti-tuberculous therapy
Show all 11Show fewer
- Age greater than or equal to 20 years old
- Contacts of index case
- QF-GIT positive
- Age greater than or equal to 20 years old
- Normal CXR
Who cannot join
- Age >60 years old
- Known diagnosis of chronic inflammatory condition (e.g. Sarcoid, RA, connective tissue disorder) or on immunosuppressive medication
- WITHDRAWAL CRITERIA:
- 1) Culture negative for M.tb
- QF-GIT Positive Contacts:
- Exposure to an index case who commenced treatment for a current episode of TB (one that was not successfully treated, per WHO definition) more than 15 months ago
Show all 19Show fewer
- Previously diagnosed or treated TB
- Symptoms or signs of active TB
- Symptoms or signs of acute illness
- CXR suggestive of active tuberculosis or parenchymal abnormalities known or suspected to be caused by alternative pathology
- HIV positive or other significant immunocompromise
- Age >60
- Smoker >30 pack years
- Previously diagnosed malignancy
- Previously diagnosed chronic lung infection (e.g., non tuberculosis mycobacteria [NTM], Fungal, Paragonimus)
- Known diagnosis of chronic inflammatory condition associated with pulmonary pathology (e.g., Sarcoidosis, RA, Wegener s granulomatosis, bronchiectasis)
- Inhaled or systemic steroid use within previous 2 weeks (subject may return for enrollment 2 weeks after last dose) and need for ongoing steroid therapy
- Breast feeding, pregnant, or planning pregnancy
- Anticipated poor compliance
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Risk Stratification in Latent Tuberculosis: PET/CT Findings in TB Contacts
Background:
- Tuberculosis (TB) is a leading cause of death worldwide. Those who are exposed to the TB bacteria but have not become sick are said to have latent TB. Many people with latent TB will not get sick from it, but some people will develop active TB and become sick. Much is known about how to treat and diagnose active TB, but little is known about the best way to treat latent TB. Researchers also want to know more about the risk that latent TB will develop into active TB, and whether it is possible to test for this risk.
Read more
Objectives:
- To test possible methods of determining a person s risk for developing active TB.
Eligibility:
- Individuals between 20 and 60 years of age who (1) have active TB, (2) were exposed to someone with active TB in the past 9 months, or (3) have not been exposed to TB.
Design:
- Participants will be separated into groups based on their exposure to TB.
- Healthy participants who were not exposed to TB will answer questions about their medical history. They will also provide blood and urine samples.
- Participants who have active TB will have a physical exam and medical history. They will provide blood, urine, and sputum samples, and will have a chest x-ray. They will be treated with the standard of care for active TB. Some participants with active TB may have additional tests as part of this study.
- Participants who were exposed to TB and have latent TB will have a physical exam and medical history. They will provide blood, urine, and sputum samples, and will have a chest x-ray. They will be asked to return for five more clinic visits over the next 12 months to repeat these tests. They may also have additional chest imaging studies depending on the study needs.
- Some of the exposed participants may have been exposed to drug-resistant TB. These participants will receive the drug isoniazid to take on a regular schedule to help prevent the latent TB from becoming active TB.
Read the detailed description
The efficacy of treating tuberculin skin test (TST) positive, or interferon gamma release assay (IGRA) positive, contacts of tuberculosis (TB) cases to prevent progression to disease is well established. However the length of treatment, and the toxicity associated with the currently used regimens, means that the risk may outweigh the benefit and treatment completion rates are poor. In addition, no proven regimens are available for contacts of multidrug resistant tuberculosis (MDR-TB) cases. Because as few as 2% of contacts develop active TB over 1 year and no surrogate markers are available, drug trials to assess novel treatments typically require thousands of subjects followed up for many years. (18F)-fluoro-2-deoxy-D-glucose positron emission tomography/computer tomography (FDG-PET/CT) may prove a useful surrogate for more targeted chemoprophylaxis as well as a means to rapidly evaluate novel prophylactic regimes in future studies.
Up to 40% of immune-sensitized TB contacts with normal chest radiographs (CXR) have abnormalities on conventional chest CT. FDG-PET/CT not only will allow characterization of the metabolic activity of these lesions but is also likely to reveal significantly increased metabolic activity within regional lymph nodes that may otherwise be anatomically normal. Based on previous studies, we predict that up to 65% of contacts will have combined chest PET/CT abnormalities and that up to 50% of contacts who are treated, will have increased FDG uptake that will resolve with treatment. By contrast, PET screening studies demonstrate abnormal pulmonary FDG uptake occurs in 0.9% of healthy individuals.
The development of biomarkers more predictive of disease progression is also highly desirable, but for similar reasons evaluating them is challenging. This novel approach of using FDG-PET/CT to benchmark the dynamic immunological, transcriptional, or metabolic changes that occur early in tuberculosis infection, we hope will accelerate biomarker discovery. In this study we propose to evaluate these predictions in order to lay the foundation for future studies.
- Conditions
- Latent Tuberculosis
- Keywords
- Biomarker, Latent Tuberculosis, IGRA, Isoniazid, TB Lymphadenopathy, Tuberculosis, TB
- Medical subject headings
- Latent Tuberculosis, Tuberculosis
What is being measured
The primary outcome is the main question the study is designed to answer.
To estimate the rate of PET plus CXR at baseline among all study participants.
Secondary outcomes (2)
To estimate the rate of PET+/CT- at baseline among all study participants.
To estimate the rate of regression of PET plus scans (to normal) at 3 and 12 months among the untreated subjects (n=30).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2012 (estimated)
- Study start2 Jan 2012
- Study completion20 May 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Latent TuberculosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Clifton E Barry, Ph.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01571739
- Sponsor's protocol ID
- 999912036
- Other IDs
- 12-I-N036
- Status last verified
- 20 May 2014
- First submitted
- 4 Apr 2012
- Last updated
- 25 Nov 2019
- Results posted
- No
Publications
Banura C, Mirembe FM, Katahoire AR, Namujju PB, Mbonye AK, Wabwire FM. Epidemiology of HPV genotypes in Uganda and the role of the current preventive vaccines: A systematic review. Infect Agent Cancer. 2011 Jul 12;6(1):11. doi: 10.1186/1750-9378-6-11.
PubMed 21749691Block SL, Nolan T, Sattler C, Barr E, Giacoletti KE, Marchant CD, Castellsague X, Rusche SA, Lukac S, Bryan JT, Cavanaugh PF Jr, Reisinger KS; Protocol 016 Study Group. Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women. Pediatrics. 2006 Nov;118(5):2135-45. doi: 10.1542/peds.2006-0461.
PubMed 17079588Centers for Disease Control and Prevention (CDC). National, state, and local area vaccination coverage among adolescents aged 13-17 years --- United States, 2009. MMWR Morb Mortal Wkly Rep. 2010 Aug 20;59(32):1018-23.
PubMed 20724968
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risk Stratification in Latent Tuberculosis: PET/CT Findings in TB Contacts
- ClinicalTrials.gov ID
- NCT01571739
- Acronym / sponsor ID
- 999912036
- Conditions
- Latent Tuberculosis
- Keywords
- Biomarker, Latent Tuberculosis, IGRA, Isoniazid, TB Lymphadenopathy, Tuberculosis, TB
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 18 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 2 Jan 2012
- Study completion
- 20 May 2014
- First posted
- 5 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Tuberculosis (TB) is a leading cause of death worldwide. Those who are exposed to the TB bacteria but have not become sick are said to have latent TB. Many people with latent TB will not get sick from it, but some people will develop active TB and become sick. Much is known about how to treat and diagnose active TB, but little is known about the best way to treat latent TB. Researchers also want to know more about the risk that latent TB will develop into active TB, and whether it is possible to test for this risk.
Objectives:
- To test possible methods of determining a person s risk for developing active TB.
Eligibility:
- Individuals between 20 and 60 years of age who (1) have active TB, (2) were exposed to someone with active TB in the past 9 months, or (3) have not been exposed to TB.
Design:
- Participants will be separated into groups based on their exposure to TB.
- Healthy participants who were not exposed to TB will answer questions about their medical history. They will also provide blood and urine samples.
- Participants who have active TB will have a physical exam and medical history. They will provide blood, urine, and sputum samples, and will have a chest x-ray. They will be treated with the standard of care for active TB. Some participants with active TB may have additional tests as part of this study.
- Participants who were exposed to TB and have latent TB will have a physical exam and medical history. They will provide blood, urine, and sputum samples, and will have a chest x-ray. They will be asked to return for five more clinic visits over the next 12 months to repeat these tests. They may also have additional chest imaging studies depending on the study needs.
- Some of the exposed participants may have been exposed to drug-resistant TB. These participants will receive the drug isoniazid to take on a regular schedule to help prevent the latent TB from becoming active TB.
Detailed description
The efficacy of treating tuberculin skin test (TST) positive, or interferon gamma release assay (IGRA) positive, contacts of tuberculosis (TB) cases to prevent progression to disease is well established. However the length of treatment, and the toxicity associated with the currently used regimens, means that the risk may outweigh the benefit and treatment completion rates are poor. In addition, no proven regimens are available for contacts of multidrug resistant tuberculosis (MDR-TB) cases. Because as few as 2% of contacts develop active TB over 1 year and no surrogate markers are available, drug trials to assess novel treatments typically require thousands of subjects followed up for many years. (18F)-fluoro-2-deoxy-D-glucose positron emission tomography/computer tomography (FDG-PET/CT) may prove a useful surrogate for more targeted chemoprophylaxis as well as a means to rapidly evaluate novel prophylactic regimes in future studies.
Up to 40% of immune-sensitized TB contacts with normal chest radiographs (CXR) have abnormalities on conventional chest CT. FDG-PET/CT not only will allow characterization of the metabolic activity of these lesions but is also likely to reveal significantly increased metabolic activity within regional lymph nodes that may otherwise be anatomically normal. Based on previous studies, we predict that up to 65% of contacts will have combined chest PET/CT abnormalities and that up to 50% of contacts who are treated, will have increased FDG uptake that will resolve with treatment. By contrast, PET screening studies demonstrate abnormal pulmonary FDG uptake occurs in 0.9% of healthy individuals.
The development of biomarkers more predictive of disease progression is also highly desirable, but for similar reasons evaluating them is challenging. This novel approach of using FDG-PET/CT to benchmark the dynamic immunological, transcriptional, or metabolic changes that occur early in tuberculosis infection, we hope will accelerate biomarker discovery. In this study we propose to evaluate these predictions in order to lay the foundation for future studies.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 20 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Either confirmed sputum smear positive and culture positive for M. tb within the last 12 months OR sputum smear positive and genotypically confirmed M.tb with culture awaited
- Age greater than or equal to 20 years old
- Genotypically confirmed sputum smear positive pulmonary tuberculosis
- Culture awaited or confirmed Mtb
- Not commenced anti-tuberculous therapy
Key exclusion criteria (19 listed)
- Age >60 years old
- Known diagnosis of chronic inflammatory condition (e.g. Sarcoid, RA, connective tissue disorder) or on immunosuppressive medication
- 1) Culture negative for M.tb
- Exposure to an index case who commenced treatment for a current episode of TB (one that was not successfully treated, per WHO definition) more than 15 months ago
- Previously diagnosed or treated TB
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To estimate the rate of PET plus CXR at baseline among all study participants.
2 secondary outcomes
To estimate the rate of PET+/CT- at baseline among all study participants.
To estimate the rate of regression of PET plus scans (to normal) at 3 and 12 months among the untreated subjects (n=30).
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2019.
- Background: PubMed 21749691Banura C, Mirembe FM, Katahoire AR, Namujju PB, Mbonye AK, Wabwire FM. Epidemiology of HPV genotypes in Uganda and the role of the current preventive vaccines: A systematic review. Infect Agent Cancer. 2011 Jul 12;6(1):11. doi: 10.1186/1750-9378-6-11.
- Background: PubMed 17079588Block SL, Nolan T, Sattler C, Barr E, Giacoletti KE, Marchant CD, Castellsague X, Rusche SA, Lukac S, Bryan JT, Cavanaugh PF Jr, Reisinger KS; Protocol 016 Study Group. Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women. Pediatrics. 2006 Nov;118(5):2135-45. doi: 10.1542/peds.2006-0461.
- Background: PubMed 20724968Centers for Disease Control and Prevention (CDC). National, state, and local area vaccination coverage among adolescents aged 13-17 years --- United States, 2009. MMWR Morb Mortal Wkly Rep. 2010 Aug 20;59(32):1018-23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clifton E Barry, Ph.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Latent Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To estimate the rate of PET plus CXR at baseline among all study participants.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01571739, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2019.