TuberculosisNCT00341601
Multi-Drug Resistant Tuberculosis in Korea
An observational study of Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in South Korea.
Trial summary
This study, conducted in Korea, will examine why some people are more susceptible to tuberculosis (TB) than others and why some strains of M tuberculosis (the bacteria that causes TB) are more difficult to treat or become resistant to drug treatments. Read more about this study
- Who is it for?
- Ages 20 years and olderHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- How many people
- 777 participants
- Where
- 2 sitesSouth Korea
- Study dates
- 3 Jan 2005to 29 Jan 2018
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- For the new cases disease group (Cohort A):
- Age greater than or equal to 20 years old;
- Primary treatment (new TB subject by WHO definition) for tuberculosis without treatment interruption (greater than or equal to 60 days) and with at least 4 months of treatment remaining;
- Clinical signs or symptoms suggestive of tuberculosis;
- Sputum AFB smear-positivity or confirmed MTB using any molecular test
- For previously treated disease group (Cohort B):
Show all 15Show fewer
- Age greater than or equal to 20 years old;
- Treated for tuberculosis previously with more than 30 days of drug treatment and either:
- a treatment interruption of greater than or equal to 60 days (includes relapse and treatment after interruption), or
- who have experienced treatment failure or have chronic TB.
- Clinical signs or symptoms suggestive of tuberculosis;
- Sputum AFB smear-positivity or confirmed MTB using any molecular test
- For healthy controls (Cohort C):
- Age greater than or equal to 20 years old;
- No previous diagnosis of TB as reported by the subject;
Who cannot join
- For TB Subjects
- 1. Women who report themselves to be pregnant or possibly pregnant during the protocol introduction and consent process (pregnant women are not normally treated at NMTH).
- For Healthy Volunteers:
- Women who report themselves to be pregnant or those found to be pregnant by a urine Beta-HCG test during the protocol introduction and consent process.
- Those having a chest X-ray suggestive of active tuberculosis.
Trial locations and contacts
2 sites in 1 country.
South Korea2 sites
National Masan Tuberculosis Hospital & Clinical Research Center
Masan
National Medical Center
Seoul
About this study
Official title: A Natural History Study of Multidrug-Resistant Tuberculosis Strains and Host Susceptibility Genes in Korean Patients With Pulmonary Tuberculosis
This study, conducted in Korea, will examine why some people are more susceptible to tuberculosis (TB) than others and why some strains of M tuberculosis (the bacteria that causes TB) are more difficult to treat or become resistant to drug treatments. The study will compare blood samples and other medical information from patients with different kinds of tuberculosis and with healthy volunteers to identify patient and bacterial characteristics that contribute to disease susceptibility, treatment failure, disease recurrence and multi-drug resistance.
Healthy volunteers and patients with tuberculosis who are 20 years of age or older may be eligible for this study. Subjects are recruited from among patients receiving treatment for tuberculosis at the National Masan Tuberculosis Hospital in the Republic of Korea and from healthy people visiting government health care centers for annual medical checkups. The latter include people who have had TB but are cured; people who have been exposed to TB, but currently have no signs of disease; and those who have not been exposed to TB.
Read more
Participants with tuberculosis undergo the following tests and procedures:
- Medical history, including past treatments for TB, and review of medical records
- Interview about home and work
- Sputum collection to test for the kind of TB bacteria present and for genetic studies of the bacteria
- Drug treatment for TB
- Blood draws as part of regular patient care, for HIV testing, and for genetic studies
- Chest x-rays as part of routine patient care
- In patients with recurrent disease, examination of the strains from both bouts of disease to determine if it is a recurrence of the same organism or infection with a new strain.
Healthy volunteers undergo the following tests and procedures:
- Brief medical history
- Blood draw to look for exposure to TB and for genetic studies
- Review of previous x-ray to look for active TB
Read the detailed description
This natural history study seeks to determine some of the mycobacterial and host factors involved in the failure of antituberculous chemotherapy, disease recurrence, and the development of multidrug resistance by M. tuberculosis. Despite optimal treatment with directly-observed short-course therapy (DOTS), about 5-10% of compliant patients with "cured" tuberculosis relapse, usually within a year after completion of therapy. In Korea, where DOTS is not practiced, the relapse rate has been reported to be 15 to 20 %. In individual patients, failure to eradicate disease contributes directly to the development of drug-resistance and to low overall cure rates. While factors such as patient drug compliance and HIV status have been extensively studied in relation to rates of relapse; host genetic factors and the specific relevance of the infecting mycobacterial strain have not yet been investigated in detail. Identification of patient characteristics and specific strains of M. tuberculosis that are associated with relapse and the evolution of drug resistance would greatly facilitate the development of treatment protocols that might avoid these complications.
Our study population will consist of subjects with pulmonary tuberculosis receiving treatment at our study sites. Healthy volunteers will be selected as the genotypic control population. All subjects with tuberculosis enrolled in the study will be followed by periodic chart review and data extraction during their treatment and follow-up at participating study sites. For 2.5 years after completing drug treatment, tuberculosis recurrence among study subjects will be identified using periodic chart abstraction and follow-up phone calls every 6 months to determine the 2 year recurrence rate for tuberculosis (TB). M. tuberculosis isolates may be collected from subjects with recurrent TB and analyzed to distinguish between relapse and re-infection.
Study subjects will be asked to provide 10 mL of blood and 5 to 30 mL of sputum for acid-fast bacilli (AFB) smear and culture at entry. Sputum will be cultured for M. tuberculosis and isolates will be tested for drug resistance (DR). The research staff may use molecular DR tests to confirm the agar-growth DR results. In addition, subjects will be asked a series of medical history questions including history of prior tuberculosis, antituberculous treatment, disease contacts, and risk factors associated with tuberculosis; and will be asked to give consent to allow clinical research staff to abstract treatment regimens and results from their inpatient and outpatient medical charts for the duration of their participation in the study (treatment and follow-up).
- Conditions
- Tuberculosis
- Keywords
- Mycobacterium Tuberculosis, TLR-2, Recurrent Tuberculosis, Phenolic Glycolipid, mRNA Expression Profiles
- Medical subject headings
- Tuberculosis
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the characteristics of subjects with relapsed tuberculosis verses the characteristics of subjects that do not experience relapse disease
Measured: Over course of the study
Secondary outcomes (2)
To compare the frequencies of the Toll-like receptor 2 and 4 (TLR2 and TLR4) alleles in tuberculosis subjects and tuberculosis-exposed, healthy volunteers. Other putative susceptibility genes discussed in the background may also be examined.
Measured: End of study
To compare molecular characteristics, including the expression of the phenolic glycolipid, (PGL) of M. tuberculosis strains that occur in subjects with a prior history of disease, disease spread to nonpulmonary sites, or previously treated disea...
Measured: End of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2006 (estimated)
- Study start3 Jan 2005
- Study completion29 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for 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
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 777 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- International Tuberculosis Research Center, National Masan Tuberculosis Hospital, Korean Center for Disease Control and Prevention
- Responsible party
- Sponsor
- Investigators
- Clifton E Barry, Ph.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00341601
- Sponsor's protocol ID
- 999905069
- Other IDs
- 05-I-N069
- Status last verified
- 29 Jan 2018
- First submitted
- 19 Jun 2006
- Last updated
- 5 Apr 2018
- Results posted
- No
Publications
Abel B, Thieblemont N, Quesniaux VJ, Brown N, Mpagi J, Miyake K, Bihl F, Ryffel B. Toll-like receptor 4 expression is required to control chronic Mycobacterium tuberculosis infection in mice. J Immunol. 2002 Sep 15;169(6):3155-62. doi: 10.4049/jimmunol.169.6.3155.
PubMed 12218133Acocella G, Conti R. Interaction of rifampicin with other drugs. Tubercle. 1980 Sep;61(3):171-7. doi: 10.1016/0041-3879(80)90007-0. No abstract available.
PubMed 7003868Agerton T, Valway S, Gore B, Pozsik C, Plikaytis B, Woodley C, Onorato I. Transmission of a highly drug-resistant strain (strain W1) of Mycobacterium tuberculosis. Community outbreak and nosocomial transmission via a contaminated bronchoscope. JAMA. 1997 Oct 1;278(13):1073-7.
PubMed 9315765Choi H, Lee M, Chen RY, Kim Y, Yoon S, Joh JS, Park SK, Dodd LE, Lee J, Song T, Cai Y, Goldfeder LC, Via LE, Carroll MW, Barry CE 3rd, Cho SN. Predictors of pulmonary tuberculosis treatment outcomes in South Korea: a prospective cohort study, 2005-2012. BMC Infect Dis. 2014 Jul 2;14:360. doi: 10.1186/1471-2334-14-360.
PubMed 24990578Song T, Park Y, Shamputa IC, Seo S, Lee SY, Jeon HS, Choi H, Lee M, Glynne RJ, Barnes SW, Walker JR, Batalov S, Yusim K, Feng S, Tung CS, Theiler J, Via LE, Boshoff HI, Murakami KS, Korber B, Barry CE 3rd, Cho SN. Fitness costs of rifampicin resistance in Mycobacterium tuberculosis are amplified under conditions of nutrient starvation and compensated by mutation in the beta' subunit of RNA polymerase. Mol Microbiol. 2014 Mar;91(6):1106-19. doi: 10.1111/mmi.12520. Epub 2014 Feb 26.
PubMed 24417450Cho E, Shamputa IC, Kwak HK, Lee J, Lee M, Hwang S, Jeon D, Kim CT, Cho S, Via LE, Barry CE 3rd, Lee JS. Utility of the REBA MTB-Rifa(R) assay for rapid detection of rifampicin resistant Mycobacterium tuberculosis. BMC Infect Dis. 2013 Oct 15;13:478. doi: 10.1186/1471-2334-13-478.
PubMed 24128118Mukundan H, Kumar S, Price DN, Ray SM, Lee YJ, Min S, Eum S, Kubicek-Sutherland J, Resnick JM, Grace WK, Anderson AS, Hwang SH, Cho SN, Via LE, Barry C 3rd, Sakamuri R, Swanson BI. Rapid detection of Mycobacterium tuberculosis biomarkers in a sandwich immunoassay format using a waveguide-based optical biosensor. Tuberculosis (Edinb). 2012 Sep;92(5):407-16. doi: 10.1016/j.tube.2012.05.009. Epub 2012 Jun 17.
PubMed 22710249
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Natural History Study of Multidrug-Resistant Tuberculosis Strains and Host Susceptibility Genes in Korean Patients With Pulmonary Tuberculosis
- ClinicalTrials.gov ID
- NCT00341601
- Acronym / sponsor ID
- 999905069
- Conditions
- Tuberculosis
- Keywords
- Mycobacterium Tuberculosis, TLR-2, Recurrent Tuberculosis, Phenolic Glycolipid, mRNA Expression Profiles
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 777 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- International Tuberculosis Research Center, National Masan Tuberculosis Hospital, Korean Center for Disease Control and Prevention
- Study start
- 3 Jan 2005
- Study completion
- 29 Jan 2018
- First posted
- 21 Jun 2006 (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.
This study, conducted in Korea, will examine why some people are more susceptible to tuberculosis (TB) than others and why some strains of M tuberculosis (the bacteria that causes TB) are more difficult to treat or become resistant to drug treatments. The study will compare blood samples and other medical information from patients with different kinds of tuberculosis and with healthy volunteers to identify patient and bacterial characteristics that contribute to disease susceptibility, treatment failure, disease recurrence and multi-drug resistance.
Healthy volunteers and patients with tuberculosis who are 20 years of age or older may be eligible for this study. Subjects are recruited from among patients receiving treatment for tuberculosis at the National Masan Tuberculosis Hospital in the Republic of Korea and from healthy people visiting government health care centers for annual medical checkups. The latter include people who have had TB but are cured; people who have been exposed to TB, but currently have no signs of disease; and those who have not been exposed to TB.
Participants with tuberculosis undergo the following tests and procedures:
- Medical history, including past treatments for TB, and review of medical records
- Interview about home and work
- Sputum collection to test for the kind of TB bacteria present and for genetic studies of the bacteria
- Drug treatment for TB
- Blood draws as part of regular patient care, for HIV testing, and for genetic studies
- Chest x-rays as part of routine patient care
- In patients with recurrent disease, examination of the strains from both bouts of disease to determine if it is a recurrence of the same organism or infection with a new strain.
Healthy volunteers undergo the following tests and procedures:
- Brief medical history
- Blood draw to look for exposure to TB and for genetic studies
- Review of previous x-ray to look for active TB
Detailed description
This natural history study seeks to determine some of the mycobacterial and host factors involved in the failure of antituberculous chemotherapy, disease recurrence, and the development of multidrug resistance by M. tuberculosis. Despite optimal treatment with directly-observed short-course therapy (DOTS), about 5-10% of compliant patients with "cured" tuberculosis relapse, usually within a year after completion of therapy. In Korea, where DOTS is not practiced, the relapse rate has been reported to be 15 to 20 %. In individual patients, failure to eradicate disease contributes directly to the development of drug-resistance and to low overall cure rates. While factors such as patient drug compliance and HIV status have been extensively studied in relation to rates of relapse; host genetic factors and the specific relevance of the infecting mycobacterial strain have not yet been investigated in detail. Identification of patient characteristics and specific strains of M. tuberculosis that are associated with relapse and the evolution of drug resistance would greatly facilitate the development of treatment protocols that might avoid these complications.
Our study population will consist of subjects with pulmonary tuberculosis receiving treatment at our study sites. Healthy volunteers will be selected as the genotypic control population. All subjects with tuberculosis enrolled in the study will be followed by periodic chart review and data extraction during their treatment and follow-up at participating study sites. For 2.5 years after completing drug treatment, tuberculosis recurrence among study subjects will be identified using periodic chart abstraction and follow-up phone calls every 6 months to determine the 2 year recurrence rate for tuberculosis (TB). M. tuberculosis isolates may be collected from subjects with recurrent TB and analyzed to distinguish between relapse and re-infection.
Study subjects will be asked to provide 10 mL of blood and 5 to 30 mL of sputum for acid-fast bacilli (AFB) smear and culture at entry. Sputum will be cultured for M. tuberculosis and isolates will be tested for drug resistance (DR). The research staff may use molecular DR tests to confirm the agar-growth DR results. In addition, subjects will be asked a series of medical history questions including history of prior tuberculosis, antituberculous treatment, disease contacts, and risk factors associated with tuberculosis; and will be asked to give consent to allow clinical research staff to abstract treatment regimens and results from their inpatient and outpatient medical charts for the duration of their participation in the study (treatment and follow-up).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age greater than or equal to 20 years old;
- Primary treatment (new TB subject by WHO definition) for tuberculosis without treatment interruption (greater than or equal to 60 days) and with at least 4 months of treatment remaining;
- Clinical signs or symptoms suggestive of tuberculosis;
- Sputum AFB smear-positivity or confirmed MTB using any molecular test
- Age greater than or equal to 20 years old;
Key exclusion criteria (5 listed)
- For TB Subjects
- 1. Women who report themselves to be pregnant or possibly pregnant during the protocol introduction and consent process (pregnant women are not normally treated at NMTH).
- Women who report themselves to be pregnant or those found to be pregnant by a urine Beta-HCG test during the protocol introduction and consent process.
- Those having a chest X-ray suggestive of active tuberculosis.
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 compare the characteristics of subjects with relapsed tuberculosis verses the characteristics of subjects that do not experience relapse disease
Time frame: Over course of the study
2 secondary outcomes
To compare the frequencies of the Toll-like receptor 2 and 4 (TLR2 and TLR4) alleles in tuberculosis subjects and tuberculosis-exposed, healthy volunteers. Other putative susceptibility genes discussed in the background may also be examined.
Time frame: End of study
To compare molecular characteristics, including the expression of the phenolic glycolipid, (PGL) of M. tuberculosis strains that occur in subjects with a prior history of disease, disease spread to nonpulmonary sites, or previously treated disea...
Time frame: End of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2018.
- Background: PubMed 12218133Abel B, Thieblemont N, Quesniaux VJ, Brown N, Mpagi J, Miyake K, Bihl F, Ryffel B. Toll-like receptor 4 expression is required to control chronic Mycobacterium tuberculosis infection in mice. J Immunol. 2002 Sep 15;169(6):3155-62. doi: 10.4049/jimmunol.169.6.3155.
- Background: PubMed 7003868Acocella G, Conti R. Interaction of rifampicin with other drugs. Tubercle. 1980 Sep;61(3):171-7. doi: 10.1016/0041-3879(80)90007-0. No abstract available.
- Background: PubMed 9315765Agerton T, Valway S, Gore B, Pozsik C, Plikaytis B, Woodley C, Onorato I. Transmission of a highly drug-resistant strain (strain W1) of Mycobacterium tuberculosis. Community outbreak and nosocomial transmission via a contaminated bronchoscope. JAMA. 1997 Oct 1;278(13):1073-7.
- Derived from this study: PubMed 24990578Choi H, Lee M, Chen RY, Kim Y, Yoon S, Joh JS, Park SK, Dodd LE, Lee J, Song T, Cai Y, Goldfeder LC, Via LE, Carroll MW, Barry CE 3rd, Cho SN. Predictors of pulmonary tuberculosis treatment outcomes in South Korea: a prospective cohort study, 2005-2012. BMC Infect Dis. 2014 Jul 2;14:360. doi: 10.1186/1471-2334-14-360.
- Derived from this study: PubMed 24417450Song T, Park Y, Shamputa IC, Seo S, Lee SY, Jeon HS, Choi H, Lee M, Glynne RJ, Barnes SW, Walker JR, Batalov S, Yusim K, Feng S, Tung CS, Theiler J, Via LE, Boshoff HI, Murakami KS, Korber B, Barry CE 3rd, Cho SN. Fitness costs of rifampicin resistance in Mycobacterium tuberculosis are amplified under conditions of nutrient starvation and compensated by mutation in the beta' subunit of RNA polymerase. Mol Microbiol. 2014 Mar;91(6):1106-19. doi: 10.1111/mmi.12520. Epub 2014 Feb 26.
- Derived from this study: PubMed 24128118Cho E, Shamputa IC, Kwak HK, Lee J, Lee M, Hwang S, Jeon D, Kim CT, Cho S, Via LE, Barry CE 3rd, Lee JS. Utility of the REBA MTB-Rifa(R) assay for rapid detection of rifampicin resistant Mycobacterium tuberculosis. BMC Infect Dis. 2013 Oct 15;13:478. doi: 10.1186/1471-2334-13-478.
- Derived from this study: PubMed 22710249Mukundan H, Kumar S, Price DN, Ray SM, Lee YJ, Min S, Eum S, Kubicek-Sutherland J, Resnick JM, Grace WK, Anderson AS, Hwang SH, Cho SN, Via LE, Barry C 3rd, Sakamuri R, Swanson BI. Rapid detection of Mycobacterium tuberculosis biomarkers in a sandwich immunoassay format using a waveguide-based optical biosensor. Tuberculosis (Edinb). 2012 Sep;92(5):407-16. doi: 10.1016/j.tube.2012.05.009. Epub 2012 Jun 17.
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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)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites 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 15 inclusion and 5 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: finished, as of the sponsor's last update on 5 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 compare the characteristics of subjects with relapsed tuberculosis verses the characteristics of subjects that do not experience relapse disease (time frame: Over course of the study). 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 NCT00341601, which also lists 7 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 5 Apr 2018.