A Trial of 2 Disease-Modifying Drugs (Metformin and N-acetylcysteine ) to Promote TB Lung Function Recovery

Summary

Tuberculosis is a leading global cause of morbidity and mortality. Even if cured, a majority patients are left with bronchiectasis and fibrosis, permanent conditions that impair lung function. Large cohort studies have confirmed that even modest loss of lung function is associated with excess mortality risk. This study will examine if two treatments, metformin and N-acetylcysteine (NAC), can promote the recovery of lung function in TB if given together with standard TB treatment. There currently are no drugs approved for this indication.

Timeline

Start

2026-01

Primary completion

2031-01

Completion

2031-07

Publications

• Results Pavan Kumar N, Padmapriyadarsini C, Nancy A, Tamizhselvan M, Mohan A, Reddy D, Ganga Devi NP, Rathinam P, Jeyadeepa B, Shandil RK, Guleria R, Singh M, Babu S. Effect of Metformin on systemic chemokine responses during anti-tuberculosis chemotherapy. Tuberculosis (Edinb). 2024 Sep;148:102523. doi: 10.1016/j.tube.2024.102523. Epub 2024 Jun 1.
• Results Kumar AKH, Kadam A, Karunaianantham R, Tamizhselvan M, Padmapriyadarsini C, Mohan A, Jeyadeepa B, Radhakrishnan A, Singh UB, Bapat S, Mane A, Kumar P, Mamulwar M, Bhavani PK, Haribabu H, Rath N, Guleria R, Khan AM, Menon J; METRIF Team. Effect of Metformin on Plasma Exposure of Rifampicin, Isoniazid, and Pyrazinamide in Patients on Treatment for Pulmonary Tuberculosis. Ther Drug Monit. 2024 Jun 1;46(3):370-375. doi: 10.1097/FTD.0000000000001149. Epub 2023 Nov 28.
• Results Padmapriydarsini C, Mamulwar M, Mohan A, Shanmugam P, Gomathy NS, Mane A, Singh UB, Pavankumar N, Kadam A, Kumar H, Suresh C, Reddy D, Devi P, Ramesh PM, Sekar L, Jawahar S, Shandil RK, Singh M, Menon J, Guleria R. Randomized Trial of Metformin With Anti-Tuberculosis Drugs for Early Sputum Conversion in Adults With Pulmonary Tuberculosis. Clin Infect Dis. 2022 Aug 31;75(3):425-434. doi: 10.1093/cid/ciab964.
• Results Mapamba DA, Sabi I, Lalashowi J, Sauli E, Buza J, Olomi W, Mtafya B, Kibona M, Bakuli A, Rachow A, Velen K, Hoelscher M, Ntinginya NE, Charalambous S, Churchyard G, Wallis RS; TB SEQUEL consortium. N-acetylcysteine modulates markers of oxidation, inflammation and infection in tuberculosis. J Infect. 2025 Feb;90(2):106379. doi: 10.1016/j.jinf.2024.106379. Epub 2025 Jan 3.
• Results Wallis RS, Sabi I, Lalashowi J, Bakuli A, Mapamba D, Olomi W, Siyame E, Ngaraguza B, Chimbe O, Charalambous S, Rachow A, Ivanova O, Zurba L, Myombe B, Kunambi R, Hoelscher M, Ntinginya N, Churchyard G. Adjunctive N-Acetylcysteine and Lung Function in Pulmonary Tuberculosis. NEJM Evid. 2024 Sep;3(9):EVIDoa2300332. doi: 10.1056/EVIDoa2300332. Epub 2024 Aug 27.

Drugs

Indications