TuberculosisPhase 3TB-MET-NACNCT07136987
A Trial of 2 Disease-Modifying Drugs (Metformin and N-acetylcysteine ) to Promote TB Lung Function Recovery
A Phase 3 study testing Metformin, N-Acetylcysteine (NAC) Treatment and Standard TB treatment in people with Tuberculosis, run by Open Source Pharma Foundation.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Metformin, N-Acetylcysteine (NAC) Treatment and Standard TB treatment
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,104 participants
- Where
- No sites listed yet
- Study dates
- Jan 2026to Jul 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide signed written consent (or, in the case of illiteracy, witnessed oral consent plus patient thumbprint) prior to undertaking any trial-related procedures.
- Body weight (in light clothing without shoes) between 30 and 90 kg.
- Radiographic evidence of pulmonary tuberculosis
- Positive Xpert TB/RIF (original or Ultra) for MTB
- RIF susceptibility diagnosed by Xpert TB/RIF, with subsequent culture confirmation
- FEV1≤65% of predicted
Show all 11Show fewer
- Eligible for treatment with a 6-month regimen comprised of INH, RIF, EMB, and PZA
- If sexually active, willing to use effective contraceptive methods for a period of 9 months (3 months post-study treatment)
- HIV-1 seronegative, or if HIV-1 seropositive, presenting to a non-India clinical site with a CD4 T cell count ≥100/µl and either receiving ART or willing to start ART during study participation
- SARS-CoV-2 PCR or antigen test negative, or if positive, either fully vaccinated against Covid-19 or with D-dimer <1 µg/ml
- eGFR ≥30 ml/min/1.73 m2 (CKD EPI 2009)
Who cannot join
- Any condition for which participation in the trial, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments
- Currently pregnant or nursing, or pregnancy planned in next 12 months
- 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.
- TB meningitis or spondylitis, or other forms of severe tuberculosis with high risk of a poor outcome as judged by the investigator.
- History of allergy or hypersensitivity to any of the trial therapies or related substances.
- History of a chronic lung condition (including COPD or asthma) requiring treatment in the previous year
Show all 15Show fewer
- Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial.
- Prior TB treatment in the preceding 6 months, other than within the 7 days immediately prior to enrollment.
- Angina pectoris requiring treatment with nitroglycerin or other nitrates
- Cardiac arrhythmia requiring medication, or any clinically significant ECG abnormality, in the opinion of the investigator
- History of diabetes mellitus requiring treatment with metformin or resulting in hospitalization for hyper- or hypoglycaemia within the past year prior to start of screening
- Use of systemic corticosteroids within the past 28 days.
- Patients requiring treatment with medications not compatible with rifampin, such as HIV-1 protease inhibitors
- History of Pneumoconiosis.
- Subjects with any of the following abnormal laboratory values: hemoglobin <8 g/dL, platelets <100x109 cells/L, serum potassium <3.5 mM/L, alanine aminotransferase (ALT) ≥2.0 x ULN, alkaline phosphatase (AP) >5.0 x ULN, total bilirubin >1.5 mg/dL, HbA1c >6.5 %
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Randomized Controlled Trial of 2 Disease-Modifying Drugs (Metformin and N-acetylcysteine ) to Promote TB Lung Function Recovery (TB-MET-NAC)
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.
Read the detailed description
Tuberculosis is a leading global cause of morbidity and mortality. Current treatments are inadequate, requiring patients closely adhere to multi-drug regimens that are long, complex, and often poorly tolerated and/or ineffective. Even if cured, a majority patients are left with bronchiectasis and fibrosis, permanent conditions that impair lung function, particularly causing loss of FEV1% (the maximal 1-second exhaled volume in relation to age, sex, and height). FEV1 loss has profound long-term health consequences. Large cohort studies have confirmed that even modest loss of FEV1, remaining within 'normal' limits, is associated with excess mortality risk. This is most pronounced in low-income countries where TB is most prevalent. This study will examine if two treatments, metformin and N-acetylcysteine (NAC), can promote the recovery of lung function in TB. There currently are no drugs approved for this indication.
- Conditions
- Tuberculosis
- Being tested
- Metformin, N-Acetylcysteine (NAC) Treatment, Standard TB treatment
- Keywords
- lung function, FEV1, relapse
- Medical subject headings
- Tuberculosis, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Metformin 500 mg QAM x 1 wk, then 500 mg BID x 1 wk, then 1000 mg QAM and 500 mg QPM, plus standard TB treatment
N-Acetylcysteine (NAC) TreatmentDietary supplement
N-acetylcysteine (NAC) 1800 mg orally twice daily plus standard TB treatment
Standard TB treatmentCombination product
Standard TB treatment
| Study group | Role | What they receive |
|---|---|---|
| Metformin plus SOC | Experimental | Metformin 1500 mg total daily for 6 months plus standard TB treatment Receives: Drug: Metformin |
| N-acetylcysteine (NAC) plus SOC | Experimental | NAC 3600 mg total daily for 6 months plus standard TB treatment Receives: Dietary Supplement: N-Acetylcysteine (NAC) Treatment |
| Control (SOC) | Active comparator | Standard TB treatment alone Receives: Combination Product: Standard TB treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
FEV1
FEV1 after adjustment for baseline covariates including FEV1, in a superiority comparison
Measured: month 18
Favourable treatment outcome
Proportion of participants achieving a favourable treatment outcome (other than death, failure, recurrence, loss, default) in a non-inferiority comparison
Measured: 18 months
Secondary outcomes (6)
Other measures of lung function
Changes in FEV1 and FVC
Measured: Through month 18
Microbiology
Clearance of MTB from sputum measured as time to stable culture conversion and as rate of change in time to detection of MTB in automated liquid cultures (MGIT TTP)
Measured: Through month 6
Pharmacology
Plasma TB drug exposures (Cmax and AUC0-24) using population PK modeling
Measured: After 1 month of TB treatment
Serious and non-serious adverse events
The numbers of serious and non-serious adverse events
Measured: Through month 18
Radiography
Proportion of patients with persisting lung cavities on chest X ray
Measured: 18 months
Immunology
Blood measurements of inflammation (CRP) and immune function (IFN)
Measured: 2, 6, and 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2025
- Study startJan 2026 (estimated)
- Primary completionJan 2031 (estimated)
- Study completionJul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized 1:1:1 to the 3 arms.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1,104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Open Source Pharma Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Research in Tuberculosis, Chennai, India
- Responsible party
- Sponsor
- Investigators
- Robert Wallis, MD, Principal investigator, OSPF and Aurum Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07136987
- Sponsor's protocol ID
- AUR1-22-465 TB-MET-NAC
- Acronym
- TB-MET-NAC
- Status last verified
- Aug 2025
- First submitted
- 5 Aug 2025
- Last updated
- 22 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized IPD will be shared after the publication of the primary trial manuscript.
Publications
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.
PubMed 38850838Kumar 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.
PubMed 38019456Padmapriydarsini 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.
PubMed 34849651Mapamba 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.
PubMed 39756697Wallis 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.
PubMed 39189858
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of 2 Disease-Modifying Drugs (Metformin and N-acetylcysteine ) to Promote TB Lung Function Recovery (TB-MET-NAC)
- ClinicalTrials.gov ID
- NCT07136987
- Acronym / sponsor ID
- TB-MET-NAC / AUR1-22-465 TB-MET-NAC
- Conditions
- Tuberculosis
- Keywords
- lung function, FEV1, relapse
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,104 participants (estimated)
- Lead sponsor
- Open Source Pharma FoundationUniversity, hospital or other
- Collaborators
- National Institute for Research in Tuberculosis, Chennai, India
- Study start
- Jan 2026 (estimated)
- Primary completion
- Jan 2031 (estimated)
- Study completion
- Jul 2031 (estimated)
- First posted
- 22 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Tuberculosis is a leading global cause of morbidity and mortality. Current treatments are inadequate, requiring patients closely adhere to multi-drug regimens that are long, complex, and often poorly tolerated and/or ineffective. Even if cured, a majority patients are left with bronchiectasis and fibrosis, permanent conditions that impair lung function, particularly causing loss of FEV1% (the maximal 1-second exhaled volume in relation to age, sex, and height). FEV1 loss has profound long-term health consequences. Large cohort studies have confirmed that even modest loss of FEV1, remaining within 'normal' limits, is associated with excess mortality risk. This is most pronounced in low-income countries where TB is most prevalent. This study will examine if two treatments, metformin and N-acetylcysteine (NAC), can promote the recovery of lung function in TB. There currently are no drugs approved for this indication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
- Model description
- Participants will be randomized 1:1:1 to the 3 arms.
| Arm | Type | Receives |
|---|---|---|
| Metformin plus SOC | Experimental | Drug: MetforminMetformin 1500 mg total daily for 6 months plus standard TB treatment |
| N-acetylcysteine (NAC) plus SOC | Experimental | Dietary Supplement: N-Acetylcysteine (NAC) TreatmentNAC 3600 mg total daily for 6 months plus standard TB treatment |
| Control (SOC) | Active comparator | Combination Product: Standard TB treatmentStandard TB treatment alone |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Willing and able to provide signed written consent (or, in the case of illiteracy, witnessed oral consent plus patient thumbprint) prior to undertaking any trial-related procedures.
- Body weight (in light clothing without shoes) between 30 and 90 kg.
- Radiographic evidence of pulmonary tuberculosis
- Positive Xpert TB/RIF (original or Ultra) for MTB
- RIF susceptibility diagnosed by Xpert TB/RIF, with subsequent culture confirmation
Key exclusion criteria (15 listed)
- Any condition for which participation in the trial, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments
- Currently pregnant or nursing, or pregnancy planned in next 12 months
- 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.
- TB meningitis or spondylitis, or other forms of severe tuberculosis with high risk of a poor outcome as judged by the investigator.
- History of allergy or hypersensitivity to any of the trial therapies or related substances.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminMetformin 500 mg QAM x 1 wk, then 500 mg BID x 1 wk, then 1000 mg QAM and 500 mg QPM, plus standard TB treatment | Drug | Metformin plus SOC |
| N-Acetylcysteine (NAC) TreatmentN-acetylcysteine (NAC) 1800 mg orally twice daily plus standard TB treatment | Dietary supplement | N-acetylcysteine (NAC) plus SOC |
| Standard TB treatmentStandard TB treatment | Combination product | Control (SOC) |
Primary outcome
FEV1
Time frame: month 18
FEV1 after adjustment for baseline covariates including FEV1, in a superiority comparison
Favourable treatment outcome
Time frame: 18 months
Proportion of participants achieving a favourable treatment outcome (other than death, failure, recurrence, loss, default) in a non-inferiority comparison
6 secondary outcomes
Other measures of lung function
Time frame: Through month 18
Microbiology
Time frame: Through month 6
Pharmacology
Time frame: After 1 month of TB treatment
Serious and non-serious adverse events
Time frame: Through month 18
Radiography
Time frame: 18 months
Immunology
Time frame: 2, 6, and 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2025.
- Results publication: PubMed 38850838Pavan 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 publication: PubMed 38019456Kumar 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 publication: PubMed 34849651Padmapriydarsini 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 publication: PubMed 39756697Mapamba 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 publication: PubMed 39189858Wallis 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.
- Individual participant dataSharing planned: Yes. Anonymized IPD will be shared after the publication of the primary trial manuscript.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Robert Wallis, MD principal investigator
OSPF and Aurum Institute
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metformin, N-Acetylcysteine (NAC) Treatment and Standard TB treatment in people with Tuberculosis, run by Open Source Pharma Foundation.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jaykumar Menon, JD (+19173020722, jaykumar.menon@ospfound.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FEV1 (time frame: month 18). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07136987, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2025.