Safety and Tolerability of Metformin in People With Tuberculosis (TB) and Human Immunodeficiency Virus (HIV)
NCT ID: NCT04930744
Last Updated: 2026-01-07
Study Results
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Basic Information
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COMPLETED
PHASE2
112 participants
INTERVENTIONAL
2021-08-26
2025-08-15
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Standard Tuberculosis Medicine
Participants will have a chance to be put on standard tuberculosis medicines (Isoniazid, Rifampicin, Ethambutol and Pyrazinamide) only. It is a combination pill pack that will be taken by mouth daily. The combination pack includes Isoniazid, Rifampicin, Ethambutol, and Pyrazinamide which they will take for 2 months. They will only take Isoniazid and Rifampicin for the last 4 months.
Isoniazid
Isoniazid, dose prescribed by participant's physician, will be taken by mouth daily. Isoniazid, is in a combination pill pack with the other standard ATT medications.
Rifampicin
Rifampicin, dose prescribed by participant's physician, will be taken by mouth daily. Rifampicin is in a combination pill pack with the other standard ATT medications.
Ethambutol
Ethambutol, dose prescribed by participant's physician, will be taken by mouth daily. Ethambutol is in a combination pill pack with the other standard ATT medications.
Pyrazinamide
Pyrazinamide, dose prescribed by participant's physician, will be taken by mouth daily. Pyrazinamide is in a combination pill pack with the other standard ATT medications.
Standard TB Medicines and Metformin
Participants will have a chance to be put on standard tuberculosis medicines (Isoniazid, Rifampicin, Ethambutol and Pyrazinamide) only. It is a combination pill pack that will be taken by mouth daily. The combination pack includes Isoniazid, Rifampicin, Ethambutol, and Pyrazinamide which they will take for 2 months. They will only take Isoniazid and Rifampicin for the last 4 months. For this arm, they will also take Metformin hydrochloride one 500 mg tablet daily starting one week after the initiation of tuberculosis medicines, then increasing to one 500 mg table twice daily through study week-12 for a total 11 weeks of metformin exposure.
Isoniazid
Isoniazid, dose prescribed by participant's physician, will be taken by mouth daily. Isoniazid, is in a combination pill pack with the other standard ATT medications.
Rifampicin
Rifampicin, dose prescribed by participant's physician, will be taken by mouth daily. Rifampicin is in a combination pill pack with the other standard ATT medications.
Ethambutol
Ethambutol, dose prescribed by participant's physician, will be taken by mouth daily. Ethambutol is in a combination pill pack with the other standard ATT medications.
Pyrazinamide
Pyrazinamide, dose prescribed by participant's physician, will be taken by mouth daily. Pyrazinamide is in a combination pill pack with the other standard ATT medications.
Metformin hydrochoride
Metformin hydrochloride 500 mg tablet once daily starting one week after the initiation of TB treatment, then increasing to study twice daily through study week-12 (11 weeks total metformin treatment).
Interventions
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Isoniazid
Isoniazid, dose prescribed by participant's physician, will be taken by mouth daily. Isoniazid, is in a combination pill pack with the other standard ATT medications.
Rifampicin
Rifampicin, dose prescribed by participant's physician, will be taken by mouth daily. Rifampicin is in a combination pill pack with the other standard ATT medications.
Ethambutol
Ethambutol, dose prescribed by participant's physician, will be taken by mouth daily. Ethambutol is in a combination pill pack with the other standard ATT medications.
Pyrazinamide
Pyrazinamide, dose prescribed by participant's physician, will be taken by mouth daily. Pyrazinamide is in a combination pill pack with the other standard ATT medications.
Metformin hydrochoride
Metformin hydrochloride 500 mg tablet once daily starting one week after the initiation of TB treatment, then increasing to study twice daily through study week-12 (11 weeks total metformin treatment).
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. HIV-1 seropositive status prior to or after screening.
3. Chest radiograph compatible with pulmonary TB.
4. Positive sputum Xpert TB/RIF or Ultra with one CT \<25.
5. RIF susceptibility diagnosed by Xpert TB/RIF or Ultra.
6. Residence within study catchment area.
7. If female of childbearing potential, willing to use contraception for the duration of study participation (Criteria for childbearing potential and for acceptable contraception). If male, willing to use condoms for the duration of metformin treatment plus 3 months after stopping metformin.
Exclusion Criteria
2. Is critically ill, and in the judgment of the investigator has a diagnosis likely to result in death during the trial or the follow-up period.
3. TB meningitis or other forms of severe TB with high risk of a poor outcome as judged by the investigator.
4. Pregnant or breastfeeding.
5. Resistance to any first-line ATTB drug demonstrated by susceptibility testing.
6. More than 14 days ATT for the current episode of TB, prior to enrollment.
7. Taking any fluoroquinolone antibiotic.
8. History of diabetes mellitus or fasting blood glucose \>7.0 mmol/L on screening evaluation
9. History of congestive heart failure, chronic liver disease, diabetes, autoimmune disease or malignancy.
10. Consumption of \>28 units (men) OR \>21 units (women) of alcohol/week (see Protocol Appendix; Alcohol Pre-Screening Checklist).
11. Use of metformin within 1 year prior to enrollment.
12. History of sensitivity to metformin.
13. Acute or chronic metabolic acidosis based on reported medical history or laboratory tests performed on screening.
14. Body mass index (BMI) \<17.0 kg/m2 on screening evaluation.
15. Peripheral blood CD4 T cell count \<50 cells/mm3 on screening evaluation.
16. Hemoglobin \<9 g/dL for males, and \<8 g/dL (women) for females on screening evaluation.
17. Platelet count \<50,000/mm3 on screening evaluation.
18. Absolute neutrophil count \<750 cells/mm3 on screening evaluation.
19. Estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m2 calculated by the CKD-EPI equation.
20. Serum bicarbonate \<18 mmol/L on screening evaluation.
21. AST or ALT ≥3 times the upper limit of normal (ULN) on screening evaluation.
22. Hepatitis B surface antigen positive.
23. Enrollment in another interventional study at any time during participation in the METHOD trial.
24. Imprisonment at the time of or after enrollment in the METHOD trial.
25. Diagnosis of active COVID-19 at the time of screening or high suspicion of active COVID-19 disease during screening.
18 Years
65 Years
ALL
No
Sponsors
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National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Aurum Institute
OTHER
A*STAR Infectious Diseases Labs
INDUSTRY
University of Cape Town
OTHER
Wits Health Consortium (Pty) Ltd
OTHER
University of Massachusetts, Worcester
OTHER
Responsible Party
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Hardy Kornfeld, MD
Professor
Principal Investigators
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Robert S Wallis, MD, FIDSA
Role: STUDY_CHAIR
Aurum Institute
Hardy Kornfeld, MD
Role: PRINCIPAL_INVESTIGATOR
The University of Massachusetts Chan Medical School
Locations
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Tembisa Clinical Research Centre-The Aurum Institute
Johannesburg, Gauteng, South Africa
Isango Lethemba TB Research Unit
Port Elizabeth, , South Africa
Countries
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References
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Other Identifiers
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AUR1-1-199
Identifier Type: -
Identifier Source: org_study_id
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