Measurement of Anti-TB Drugs in Lung Tissue From Patients Having Surgery to Treat Tuberculosis

• Status: Completed
• Trial end date: 2017-12-29
• Target enrollment: 0
• Participant gender: All

Summary

This study, conducted jointly by researchers at the National Masan TB Hospital, Asan and Samsung Medical Centers in Seoul, Republic of Korea, and the Yonsei University and the NIH in the United States, will examine why some patients with tuberculosis (TB) develop disease that is harder to treat than most cases. TB is an infection of the lung that usually can be successfully treated with anti-TB drugs. However, some people get a more serious kind of disease (called multi-drug resistant TB or extensively drug-resistant TB) that is very difficult to treat and may not be cured by the regular medicines available. This study will try to find out if some of the common TB drugs are getting to the place where the TB bacteria are. It will also look at how current anti-TB drugs might be used more effectively and how better drugs might be developed.

People 20 years of age and older with hard-to-treat TB who have elected to undergo surgical removal of part of their lung at the National Masan Tuberculosis Hospital, Masan, the Asan Medical Center, and the Samsung Medical Center, may be eligible for this study.

Participants undergo the following procedures:

• Medical history and physical examination, including sputum sample.

• Blood tests at various times during the study.

• Drug administration. Subjects are given one dose each of five common TB drugs rifampicin, isoniazid, pyrazinamide, kanamycin and moxifloxacin before they undergo surgery to remove part of their lung. After surgery, some of the lung tissue and fluid around the lungs that was removed during surgery will be examined to determine the regions where the TB bacteria live and analyze the lung tissue itself.

• Dynamic MRI (magnetic resonance imaging) scan. This type of scan uses a magnetic field and radio waves to produce pictures of the lung. Subjects lie very still on a table inside the cylindrical scanner with their head on a soft cradle and their hands over their head. Several images are obtained for less than 5 minutes at a time.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Asian Medical Center; International Tuberculosis Research Center; Korean Center for Disease Control and Prevention; Novartis Institute for Tropical Medicine
• Treatments: Fluoroquinolones; Isoniazid; Kanamycin; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination; Pyrazinamide; Rifampin

Criteria

• INCLUSION CRITERIA:

1. Males and females age 20 and above

2. Selected for lung resection due to anti-tuberculous treatment failure, multidrug resistant disease, or other reason determined by the treating physician

3. Radiographic evidence of tuberculous disease of the lung(s)

4. If already on an aminoglycoside, ability and willingness to substitute this aminoglycoside with KM for the one study dose

5. Willingness to receive MRI scan and marker and Gadolinium injection

6. Willingness to have samples stored

7. Ability and willingness to give written or oral informed consent

EXCLUSION CRITERIA:

1. Subjects less than 20 years of age

2. Women of childbearing potential who are pregnant, breast feeding, or unwilling to avoid pregnancy (i.e., the use of appropriate contraception including oral and subcutaneous implantable hormonal contraceptives, condoms, diaphragm, intrauterine device (IUD), or abstinence from sexual intercourse) [Note: Prospective female participants of childbearing potential must have negative pregnancy test (urine) within 48 hours prior to study entry.]

3. Allergy or hypersensitivity to any of the 5 study drugs, any aminoglycoside, or rifamycin (those allergic to fluoroquinolones will not receive MXF).

4. Those with severe gout

5. Severe claustrophobia or Gadolinium hypersensitivity (tbc)

6. Renal, hepatic, auditory and/or vestibular impairment.

1. Serum creatinine greater than 2.0 mg/dL (renal)

2. Aspartate aminotransferase (AST or SGOT) greater than 100 IU/L (LFTs)

3. Alanine aminotransferase (ALT or SGPT) greater than 100 IU/L (LFTs)

4. Total bilirubin greater than 2.0 mg/dL (LFTs)

7. The use of any of Rifampicin (RIF), Rifapentine or Rifabutin within 30 days prior to the study

8. HIV infection, determined by a positive HIV test performed with the past 6 months

9. The use of any of the following drugs within 30 days prior to study:

1. Systemic cancer chemotherapy

2. Systemic corticosteroids (oral or IV only) with the following

exceptions (i.e.the following are NOT exclusion criteria): intranasal, topical, and inhaled corticosteroids, a short course (10 days or less) of corticosteroids for a non-chronic condition completed at least 2 weeks prior to enrollment in this study

3. Systemic IND agents other than Linezolid

4. Antiretroviral medications

5. Growth factors

10. The need for ongoing therapy with warfarin, phenytoin, lithium cholestrymine, levodopa, cimetidine, disulfiram, ergot derivatives, fosphenytoin, carbamazepine, cyclosporine, tacrolimus, sirolimus, amiodarone or Phenobarbital (If a potential subject is on one of these medications but it is being stopped per standard of care, to be eligible for the study the drug must be stopped at least one day prior to receiving study drug. A longer washout period is not necessary.) The only exception to this is amiodarone; because of amiodarone s long half-life and potential for QT prolongation, it should be stopped at least 60 days prior to receiving study drugs.