A Clinical Trial to evaluate whether NAC and Metformin can aid lung recovery post TB

Phase 3

Not yet recruiting

• Conditions: Tuberculosis of lung,

• Registration Number: CTRI/2025/06/088763
• Lead Sponsor: Indian Council of Medical Research (ICMR)

Brief Summary

A multi-centric RCT is being conducted to determine the effectof 2 adjunctive disease modifying drugs (N-acetylcysteine (NAC) and Metformin)in promoting  recovery of lung functionpost-TB in persons with Rifampicin susceptible tuberculosis and impaired lungfunction at baseline. The main study outcomes are improvement in FEV1, culture conversion, favorable treatment outcomes and safety. The trial sample size will be 1104 and will be conducted in India, Brazil and China (yet to be confirmed). The participants with FEV1 less than 65 percent will be enrolled. This study will generateevidence to support use of these 2 adjuvants (NAC and Metformin) in improvingthe Lung function impairment in Drug susceptible adult tuberculosis patients.

Detailed Description

Not available

Study Timeline

• Study Start: 2025-01-07
• Last Update Posted: 2025-11-06

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• 1.Aged 18 to 65 years 2.Willing and able to provide signed written consent prior to undertaking any trial-related procedures.
• Or, in the case of illiteracy, witnessed oral consent plus patient thumbprint.
• 3.Body weight (in light clothing without shoes) between 30 and 90 kg.
• 4.Radiographic evidence of pulmonary tuberculosis 5.Positive Xpert TB RIF (original or Ultra) for MTB.
• 6.RIF susceptibility diagnosed by Xpert TB RIF, with subsequent culture confirmation 7.Eligible for treatment with a 6-month regimen comprised of INH, RIF, EMB, and PZA.
• 8.FEV1 less than or equal to 65 percent of predicted 9.Willing to use effective contraception for the first 9 months of study participation 10.HIV-1 seronegative, or if HIV-1 seropositive: presenting at a non-India study site with CD4 T cell count less than or equal to 100 per µl and either receiving ART or willing to start ART during study participation 11.SARS-CoV-2 PCR or antigen test negative, or if positive, either fully vaccinated against Covid-19 (having had the full primary series of 1-2 doses according to approved schedules) or with D-dimer less than 1 µg per ml.

Exclusion Criteria

• 1.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 2.Currently pregnant or nursing.
• 3.Is critically ill.
• 4.TB meningitis or spondylitis, or other forms of severe tuberculosis 5.History of allergy or hypersensitivity to any of the trial therapies or related substances.
• 6.History of a chronic lung condition (including COPD or asthma) requiring treatment in the previous year 7.Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial.
• 8.Prior TB treatment in the preceding 6 months, other than within the 7 days immediately prior to enrollment.
• 9.Angina pectoris requiring treatment with nitroglycerin or other nitrates 10.Cardiac arrhythmia requiring medication, or any clinically significant ECG abnormality, in the opinion of the investigator 11.History of Diabetes Mellitus requiring metformin treatment or resulting in hospitalization for hyper- or hypoglycemia within the past year prior to start of screening.
• 12.Use of systemic corticosteroids within the past 28 days.
• 13.Patients requiring treatment with medications not compatible with rifampin, such as HIV-1 pro-tease inhibitors 14.History of Pneumoconiosis 15.Subjects with any of the following abnormal laboratory values: a.
• creatinine greater than2 mg per dL b.
• haemoglobin less than 8 g per dL c.
• platelets less than 100x109 cells per L d.
• serum potassium less than 3.5 mM per L e.
• alanine aminotransferase (ALT) less than or equal to 2.0 x ULN f.
• alkaline phosphatase (AP) greater than 5.0 x ULN g.
• total bilirubin greater than 1.5 mg per dL h.
• HbA1c of greater than 6.5 percent will be excluded.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
FEV1 at month 18, after adjustment for baseline covariates including FEV1, in a superiority comparison	At month 18 (12 months post-End of treatment[EOT])
The proportion of patients achieving a satisfactory (favourable)outcome assessed at month 18 (12 months post-End of treatment[EOT]), after ad-justment for baseline covariates, in a non-inferiority comparison, with supe-riority testing to follow if NI is determined	At month 18 (12 months post-End of treatment[EOT])

Secondary Outcome Measures

Name	Time	Method
FEV1 and FVC modelled throughout the study period by linear mixed effects modelling. The hazard ratio for stable culture conversion (HR SCC) through the 6th month of treatment. The proportion of subjects with TE ALT increases, graded according to se-verity	At 18 month

Trial Locations

Locations (2)

ICMR-NIRT; 🇮🇳 Chennai, TAMIL NADU, India

NITRD, New Delhi; 🇮🇳 South, DELHI, India

ICMR-NIRT

🇮🇳Chennai, TAMIL NADU, India

Dr PK Bhavani

Principal investigator

9962934169

bhavani.pk@icmr.gov.in