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CTRI Number  CTRI/2025/06/088763 [Registered on: 12/06/2025] Trial Registered Prospectively
Last Modified On: 11/06/2025
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   A Clinical Trial to evaluate whether NAC and Metformin can aid lung recovery post TB  
Scientific Title of Study   A randomized Clinical trial to determine the effect of 2 adjunctive disease modifying drugs (N-acetylcysteine (NAC) and Metformin) in promoting recovery of lung function post-TB in patients with Rifampicin susceptible tuberculosis and impaired lung function at baseline (TB-DMD) 
Trial Acronym  TB-DMD trial 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr PK Bhavani 
Designation  Scientist - E (Medical) 
Affiliation  ICMR - National Institute for Research in Tuberculosis (NIRT) 
Address  Department of Clinical research, No.1, Mayor Sathyamoorthy road, Chetpet, Chennai - 600031

Chennai
TAMIL NADU
600031
India 
Phone  9962934169  
Fax    
Email  bhavani.pk@icmr.gov.in   
 
Details of Contact Person
Scientific Query  
Name  Dr PK Bhavani 
Designation  Scientist - E (Medical) 
Affiliation  ICMR - National Institute for Research in Tuberculosis (NIRT) 
Address  Department of Clinical research, No.1, Mayor Sathyamoorthy road, Chetpet, Chennai - 600031

Chennai
TAMIL NADU
600031
India 
Phone  9962934169  
Fax    
Email  bhavani.pk@icmr.gov.in   
 
Details of Contact Person
Public Query  
Name  Dr PK Bhavani 
Designation  Scientist - E (Medical) 
Affiliation  ICMR - National Institute for Research in Tuberculosis (NIRT) 
Address  Department of Clinical research, No.1, Mayor Sathyamoorthy road, Chetpet, Chennai - 600031

Chennai
TAMIL NADU
600031
India 
Phone  9962934169  
Fax    
Email  bhavani.pk@icmr.gov.in   
 
Source of Monetary or Material Support  
Indian council of Medical Research, V. Ramalingaswami Bhawan, P.O. Box No. 4911, Ansari Nagar, New Delhi - 110029, India 
 
Primary Sponsor  
Name  Indian Council of Medical Research (ICMR) 
Address  V. Ramalingaswami Bhawan, PO Box No. 4911 Ansari Nagar, New Delhi - 110029, India 
Type of Sponsor  Government funding agency 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 2  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr PK Bhavani  ICMR-NIRT  Department of Clinical research, No.1, Mayor Sathyamoorthy road, Chetpet, Chennai - 31
Chennai
TAMIL NADU 		 9962934169

bhavani.pk@icmr.gov.in  
Dr J K Saini   NITRD, New Delhi  Head, Department of Thoracic Oncology, Sri Aurobindo Marg,Near Qutub Minar New Delhi-110030
South
DELHI 		 9818012841

jk.saini@nitrd.nic.in 
 
Details of Ethics Committee  
No of Ethics Committees= 2  
Name of Committee  Approval Status 
Institutional Ethics Committee- LSR institute of tuberculosis & respiratory Disease  Submittted/Under Review 
NIRT - Institutional Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Notified 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: A150||Tuberculosis of lung,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Metformin  Along with standard ATT, Metformin will be given at a dose of 500mg once daily in the morning (QAM) for the first week, fol-lowed by 500mg BID for 1 week, then 1000mg OD in the morning (QAM) plus 500mg in the night (QPM) for the remainder of the 6 month treatment period. Metformin will be provided as 500mg immediate release (IR) tablets. Sustained release tablets will not be used due to an as of yet unresolved concern regarding nitrosamine contamination. 
Intervention  NAC (N- Acetyl Cysteine)  Along with standard ATT, NAC will be given at a dose of 1200 mg twice daily, also for 6 months.NAC will be provided as 600mg capsules from NOW Foods, as was done in the NAC-TB study. The prod-uct is classified by US FDA as nutritional supplement. NAC and TB drug dosing will be separated by a minimum of 2 hours.  
Comparator Agent  Standard ATT  6-month TB treatment with INH, RIF, EMB and PZA given once daily as fixed dose combination tablets at standard doses according to national guidelines 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  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
 
 
ExclusionCriteria 
Details  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.
 
 
Method of Generating Random Sequence   Stratified block randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
FEV1 at month 18, after adjustment for baseline covariates including FEV1, in a superiority comparison
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  
Outcome  TimePoints 
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 
 
Target Sample Size   Total Sample Size="500"
Sample Size from India="500" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   01/07/2025 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="3"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Yet Recruiting 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary   A multi-centric RCT is being conducted to determine the effect of 2 adjunctive disease modifying drugs (N-acetylcysteine (NAC) and Metformin) in promoting  recovery of lung function post-TB in persons with Rifampicin susceptible tuberculosis and impaired lung function 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 generate evidence to support use of these 2 adjuvants (NAC and Metformin) in improving the Lung function impairment in Drug susceptible adult tuberculosis patients. 
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