Multi-Drug Resistant Tuberculosis in Korea

April 4, 2018 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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.

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

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

777

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Masan, Korea, Republic of
        • National Masan Tuberculosis Hospital & Clinical Research Center
      • Seoul, Korea, Republic of
        • National Medical Center

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.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

  • INCLUSION CRITERIA:

For the new cases disease group (Cohort A):

  1. Age greater than or equal to 20 years old;
  2. 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;
  3. Clinical signs or symptoms suggestive of tuberculosis;
  4. Sputum AFB smear-positivity or confirmed MTB using any molecular test

For previously treated disease group (Cohort B):

  1. Age greater than or equal to 20 years old;

  2. Treated for tuberculosis previously with more than 30 days of drug treatment and either:

    1. a treatment interruption of greater than or equal to 60 days (includes relapse and treatment after interruption), or
    2. who have experienced treatment failure or have chronic TB.
  3. Clinical signs or symptoms suggestive of tuberculosis;
  4. Sputum AFB smear-positivity or confirmed MTB using any molecular test

For healthy controls (Cohort C):

  1. Age greater than or equal to 20 years old;
  2. No previous diagnosis of TB as reported by the subject;

EXCLUSION CRITERIA:

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:

  1. 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.
  2. Those having a chest X-ray suggestive of active tuberculosis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Over course of the study

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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
End of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Korean Center for Disease Control and Prevention
International Tuberculosis Research Center
National Masan Tuberculosis Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 Major Dates

Study Start

January 3, 2005

Study Completion

January 29, 2018

Study Registration Dates

First Submitted

June 19, 2006

First Submitted That Met QC Criteria

June 19, 2006

First Posted (Estimate)

June 21, 2006

Study Record Updates

Last Update Posted (Actual)

April 5, 2018

Last Update Submitted That Met QC Criteria

April 4, 2018

Last Verified

January 29, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 999905069
  • 05-I-N069

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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