Tuberculosis Respiratory
Conditions
Sponsors
University of Cape Town
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has completed the written informed consent process prior to undergoing any pre-screening or screening evaluations and willing to undergo HIV testing 2. Age 18 to 65 years with body weight from 50 kg to 90 kg 3. Clinical response to TB treatment and sputum culture negative at week 16 4. Completed a course of standard TB treatment Laboratory parameters within 30 days before enrolment: 5. For HIV-infected participants: suppressed HIV viral load within 30 days prior to enrolment 6. AST and ALT 7.0 g/dL 9. Platelet count >50 x109 cells/L 10. Creatinine kinase <2x ULN 11. Able and willing to return to follow-up 12. Willing to have samples, including DNA, stored 13. Willing to consistently practice a highly reliable method of pregnancy prevention
Exclusion criteria
Exclusion criteria: 1. Acute illness 2. Fever (temperature >38.0 degrees centigrade) 3. Participant receiving any type of lipid lowering agent at the time of screening, within three months prior to screening or likely to require any lipid lowering agent in the near future. 4. Known allergy or contraindications to the investigational drug or any other statins 5. Any drug with significant drug-drug interaction that increase exposure to atorvastatin and potentially the risk for the participants (E.g. protease inhibitors) 6. Evidence of drug-resistant TB 7. Extrapulmonary TB, including pleural TB and/or large pleural effusion 8. Pregnant or desiring/trying to become pregnant in the next 6 months 9. Unable to take oral medications 10. Diabetes as defined by HbA1c=6.5, random glucose=200mg/dL (or 11.1mmol/L), fasting plasma glucose=126mg/dL (or 7.0mmol/L), or the presence of any anti-diabetic agent as a concomitant medicine 11. Disease complications or concomitant illnesses that may compromise safety or interpretation of trial endpoints, such as known diagnosis of chronic inflammatory condition (e.g. sarcoidosis, rheumatoid arthritis, connective tissue disorder) 12. Use of immunosuppressive medications, such as TNF-alpha inhibitors or systemic or inhaled corticosteroids, within the past 2 weeks 13. Use of any investigational drug in the previous 3 months 14. Alcohol and substance abuse which might interfere with medication adherence during the trial 15. Any person for whom the physician feels this study is not appropriate 16. Positive SARS-CoV-2 PCR or SARS-CoV-2 Rapid Antigen Test in the past 4 weeks 17. Claustrophobia - only for patients opting to undergo cardiac MRI 18. Pacemaker, bullet injury or ferromagnetic device or surgical clip (e.g. brain aneurysm clip, aortic clip, heart valve, insulin pump, IUD, joint replacement, protheses, wire sutures, dentures) - only for patients opting to undergo cardiac MRI 19. Allergy to CMR contrast media - only for patients opting to undergo cardiac MR
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare persistent lung inflammation measured by total lung glycolysis (TLG) on PET/CT after 12 weeks of 40 mg atorvastatin therapy and placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To compare safety profile including laboratory findings, HIV viral load and CD4 count after 12 weeks of atorvastatin therapy and placebo. 2. To compare persistent lung damage measured by hard volume and cavity air volume on PET/CT after 12 weeks of atorvastatin therapy and placebo. 3. To compare pulmonary functions by spirometry, lung volumes, oxygen desaturation, and 6-minute walk test (6MWT) after 12 weeks of atorvastatin therapy and placebo. 4. To evaluate whether atorvastatin therapy reduces the proportion of participants with TB relapse by sputum reversion at 12- and 24-weeks post treatment by allocation. 5. To compare sputum culture reversion rates to Xpert® MTB/RIF Ultra and PET/CT at 12 weeks post treatment by allocation. 6. To compare changes on PET/CT after 12 weeks of atorvastatin therapy and placebo to baseline PET/CT. 7. To evaluate the effect of atorvastatin therapy on serum low-density lipoprotein (LDL) cholesterol levels by lipid profiling at 2, 4, 8, 12- and 24-weeks post treatment by allocation. 8. To compare the immunological and blood biomarkers, blood transcriptional and proteomic profiling by ELISA/Luminex, RNAseq, mass spectrometry and macrophage assays (phagosomal, autophagy and ex vivo Mtb growth) after 2, 4, 8 and 12 weeks of atorvastatin therapy and placebo, and at week 24. 9. To compare the immunological and blood biomarkers, blood transcriptional and proteomic profiling by ELISA/Luminex, RNAseq, mass spectrometry and macrophage assays (phagosomal, autophagy and ex vivo Mtb growth) of participants with no or minimal persistent inflammation on baseline PET/CT (TLG<50SUV*mL) to participants with extensive persistent inflammation on baseline PET/CT (TLG=50SUV*mL) and week 12 and 24 after enrolment. 10. To compare week 24 sputum culture reversion rates, Xpert® MTB/RIF Ultra of participants with no or minimal persistent inflammation on baseline PET/CT (TLG<50SUV*mL) to participants with extensive persistent inflammation on baseline | — |
Countries
South Africa
Contacts
Public ContactNosie Mkuzangwe
University of Cape Town
Outcome results
None listed