A Phase 2 interventional study of Nitazoxanide and Control in Tuberculosis, sponsored by Weill Medical College of Cornell University. Completed at 1 site in Haiti. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2020-08-05.
Sponsored by Weill Medical College of Cornell University · Phase 2, Interventional, and Treatment
This research is being done to determine if Nitazoxanide (NTZ) will cause a significant decrease in the number of M. tuberculosis bacteria in sputum after 14 days of treatment. The study is being conducted at the GHESKIO Centers in Port au Prince Haiti
This is a prospective randomized two-arm 14-day, early bactericidal activity study in treatment-naive, drug-susceptible patients with uncomplicated pulmonary tuberculosis (TB). The study will be conducted at the GHESKIO Centers in Port au Prince Haiti. Twenty patients will be randomized to receive NTZ 1 gram orally twice daily for 14 days. Ten patients will be randomized as positive controls to receive standard 4 drug tuberculosis therapy with isoniazid (H), rifampin (R), ethambutol (E), and pyrazinamide (PZA). Patients' sputum will be collected before and then every two days during 14 days of treatment, and the primary endpoint will be the change in the number of M. tuberculosis in patients' sputum. Our primary hypothesis is that NTZ will result in a significant decrease in the number of M. tuberculosis in sputum during14 days of treatment. The number of M. tuberculosis will be quantified by the time to positive (TTP) signal in hours in an automated liquid media culture system (BACTEC MGIT 960, Becton Dickinson).
Exclusion Criteria:
Participants with drug-sensitive tuberculous randomized to the NTZ arm will receive nitazoxanide 1000 mg po twice daily for 14 days. After this time point, participants will be switched to WHO standard tuberculosis therapy with isoniazid, rifampin, pyrazinamide and ethambutol.
Drug: Nitazoxanide
Participants with drug-sensitive tuberculosis randomized to the standard therapy arm will receive WHO standard tuberculosis therapy involving isoniazid 300 mg po daily, rifampin 600 mg po daily, pyrazinamide 25 mg/kg po daily and ethambutol 15 mg/kg po daily.
Other: Control
nitazoxanide 1000 mg orally twice daily with food for 14 days
Also known as: Nizonide, Alinia
The control arm will receive WHO standard therapy for tuberculosis with isoniazid, rifampin, pyrazinamide, and ethambutol
time to positivity (TTP)
To assess the change in time in hours to positive (TTP) signal in an automated liquid media culture system (BACTEC MGIT 960, Becton Dickinson) in participants receiving NTZ over 14 days
Time frame: first 14 days of anti-tuberculosis therapy
Number of participants with treatment-related adverse events as determined by DAIDS toxicity tables
To assess the safety of 1000 mg twice daily dosing of NTZ in participants with drug-sensitive tuberculosis by grading each treatment-related adverse reaction according the DAIDS Toxicity tables (November 2014)
Time frame: first 14 days of anti-tuberculosis therapy
Maximum plasma concentration of NTZ
To assess the maximum plasma concentration of NTZ via collection of whole blood samples at hours 2, 4, 6 after ingestion of 1000 mg NTZ on day 5 and day 14 of the study
Time frame: first 14 days of anti-tuberculosis therapy
Most probable number of M tuberculosis in 1 ml of sputum
To quantify the number of M. tuberculosis (MTB) in sputum at baseline and at day 14 using most probable number (MPN) micro-plate assay with and without resuscitation factors added to media
Time frame: first 14 days of anti-tuberculosis therapy
First-line drug susceptibility (DST) of Mycobacterium tuberculosis via Mycobacterial Growth Indicator System (MGIT)
To test for first-line drug susceptibility (DST) of Mycobacterium tuberculosis to isoniazid, rifampin, pyrazinamide and ethambutol via MGIT
Time frame: first 14 days of anti-tuberculosis therapy
Quantification of change in urine metabolites and correlation with change in TTP
To quantify the change in urine metabolites by LC-MS technology and the correlation of this change with change in TTP.
Time frame: first 14 days of anti-tuberculosis therapy
Minimum plasma concentration of NTZ
To assess the minimum plasma concentration of NTZ via collection of whole blood samples at 30 minutes prior to ingestion of 1000 mg of NTZ on day 5 and day 14 of the study
Time frame: first 14 days of anti-tuberculosis therapy
Area under the curve of NTZ metabolites
To assess the area under the curve of NTZ metabolites (tizoxanide, tizoxanide glucuronide) via collection of whole blood samples at hour 2, 4, and 6 post-ingestion of 1000 mg of NTZ on day 5 and day 14
Time frame: first 14 days of anti-tuberculosis therapy
Sputum concentration of NTZ
To assess the sputum concentration of NTZ via collection of spot sputum samples 4 hours post-ingestion of 1000 mg NTZ on day 5 and day 14 of study
Time frame: first 14 days of anti-tuberculosis therapy
Change in Minimum inhibitory concentration (MIC) of NTZ against Tuberculosis over 14 days
To assess the MIC of NTZ against tuberculosis using microplate assay at baseline and again at day 14 to determine any change in the MIC over the course of treatment
Time frame: first 14 days of anti-tuberculosis therapy
Change in phylogeny of bacteria determined by sequencing of amplified 16S ribosomal DNA and/or metagenomic sequencing of bacterial DNA
Change in phylogeny of bacteria determined by sequencing of amplified 16S ribosomal DNA and/or metagenomic sequencing of bacterial DNA over the course of 14 days and correlation of this change with change in TTP.
Time frame: first 14 days of anti-tuberculosis therapy
Transcriptional signature of treatment response using whole blood transcriptional profiles
Determine the transcriptional signature of treatment response using whole blood transcriptional profiles obtained at baseline and day 14
Time frame: first 14 days of anti-tuberculosis therapy
Plan to share: Yes — Data will be shared once the trial is complete. Data is currently being analyzed.
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Weill Medical College of Cornell University