NexGen EBA Radiologic and Immunologic Biomarkers of Sterilizing Drug Activity in Tuberculosis

• Status: Completed
• Trial end date: 2017-11-14
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• Tuberculosis (TB) is a lung infection caused by bacteria. When people with TB cough, they may spread these bacteria. Researchers are looking for new TB medicines. They want to find a faster way to tell if a drug might combat TB.

Objective:

• To learn the effect of different anti-TB drugs on microbiological, radiographic and immunologic markers in people with TB.

Eligibility:

• Adults age 18-65 who weigh 30-90 kg and have common TB bacteria that can be treated with common TB medicines.

Design:

• Participants will be admitted to the hospital for screening. They will have medical history, physical exam, and chest radiograph. They will give blood, urine, and sputum samples.

• Participants will be put in 1 of 8 groups.

• Participants will get one or a combination of TB medicines daily for about 14 days.

• Each day, participants:

• Will discuss side effects.

• May have a physical exam.

• Will spit mucus into a cup. They may breathe in saline water through a nebulizer to make them cough.

• Participants will have blood taken 3-4 times during the study

• Participants will have 2-3 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) scans. FDG is a radioactive sugar molecule which helps measure TB disease in the lungs. It will be injected into a vein. Participants will lie in a scanner that takes pictures.

• Around study day 14, participants will leave the hospital. They will be referred to a local TB clinic. There they will get the standard 4 TB medicines. Those in group 8 will already be on these medicines and will have another FDG-PET/CT on day 28.

• Participants will be in the study for up to 28 days.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Moxifloxacin; Rifampin

Criteria

• INCLUSION CRITERIA:

1. Age 18 to 65 years with body weight from 30 kg to 90 kg

2. Sputum acid-fast bacilli (AFB) smear positive (at least 1+ on the WHO International Union Against Tuberculosis and Lung Disease scale)

3. Likely able to produce approximately 10 mL of sputum per day

4. Xpert MTB/RIF-confirmed M.tb

5. Rifampin-sensitive pulmonary tuberculosis as indicated by Xpert MTB/RIF

6. ALT <3X upper limit of normal, creatinine <2X upper limit of normal

7. Willingness to have samples stored

EXCLUSION CRITERIA:

1. Clinically suspected disseminated TB or acuity of illness too much as deemed by clinicians

2. Has been treated for tuberculosis within the past 3 years

3. Treatment with agents known to have anti-tuberculosis activity (e.g., fluoroquinolones, linezolid) for any indications during the current episode of clinical illness or within 2 months prior to screening, whichever is longer

4. Cirrhosis or chronic kidney disease

5. Disease complications or concomitant illness that might compromise safety or the interpretation of trial endpoints, such as known diagnosis of chronic inflammatory condition (e.g., sarcoidosis, rheumatoid arthritis, and connective tissue disorder)

6. Use of immunosuppressive medications, such as TNF-alpha inhibitors or systemic or inhaled corticosteroids, within 2 weeks prior to screening

7. Subjects with diabetes, point of care HbA1c above 6.5, or random glucose over 200 mg/dL

8. Conditions which compromise the subject s ability to take or absorb oral drugs

9. Normal PA-Chest radiograph, determined during screening

10. Total lung (left or right) collapse on PA-Chest radiograph

11. HIV positive

12. Pregnant or breastfeeding

13. Any other condition that, in the responsible clinician s judgment, renders a subject too sick to safely tolerate 2 weeks study therapy

14. Any condition that constitutes a contraindication to any of the drugs to be used on any study arms