Efficacy of Metformin for Sputum Conversion in Patients With Active Pulmonary Tuberculosis

Efficacy of Metformin for Sputum Conversion in Patients With Active Pulmonary Tuberculosis: A Randomized Controlled Trial

This study was a randomized controlled trial studying about acid-fast bacillus sputum conversion ratio from positive to negative of pulmonary tuberculosis patients between metformin with pulmonary tuberculosis standard treatment group and placebo drug with pulmonary tuberculosis standard treatment.

Study Overview

• Status: Recruiting
• Conditions: Tuberculosis, Pulmonary
• Intervention / Treatment: Drug: MetFORMIN 500 Mg Oral Tablet; Drug: Placebo

Detailed Description

1. Pulmonary tuberculosis Patients with presence of at least one acid-fast bacillus in the sputum will be examined by an internist.
2. Collect the necessary basic information of patients who agree to participate in the treatment such as complete blood count, blood urea nitrogen, creatinine, liver function test, fasting plasma glucose, hemoglobinA1C, lactate, and gene expression signature for tuberculosis.
3. Patients will be randomized into 2 groups: those who will receive metformin with pulmonary tuberculosis standard treatment and those who will receive placebo drug with pulmonary tuberculosis standard treatment.
4. Patients will get a chest x-ray and collect sputum acid fast bacillus, sputum culture for tuberculosis and collect blood sample laboratory such as complete blood count, liver function test, creatinine, fasting plasma glucose, lactate, and gene expression signature for tuberculosis at second week.
5. Patients will get a chest x-ray and collect sputum acid fast bacillus, and sputum culture for tuberculosis at second month.
6. Patients will get a chest x-ray and collect sputum acid fast bacillus, and sputum culture for tuberculosis at fifth month.
7. Patients will get a chest x-ray and collect sputum acid fast bacillus, and sputum culture for tuberculosis at sixth month.
8. After collecting all information of patients, Investigators will analyze in clinical and statistical analysis.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Thailand
  • ฺBangkok
    • Ratchathewi, ฺBangkok, Thailand, 10400
      • Recruiting
      • Angsana Phuphuakrat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age more than 18 years old
• Be diagnosed pulmonary tuberculosis compatible with clinical and chest x ray by an internist
• Presence of at least one acid -fast bacillus in the sputum
• Recieve pulmonary tuberculosis standard treatment compose of isoniazid, rifampicin, pyrazinamide and ethambutol
• BMI more than 18.5 kg/m2
• Reserach participants were diagnosed diabetes or non diabetes.
• Research participants or representatives are welcome to join the project by signing.

Exclusion Criteria:

• Pregnancy
• Organ transplants
• eGFR less than 45 ml/min/1.73 m2
• AST, ALT or total bilirubin more than three times
• Researh participants have received metformin at least 2 weeks before joining the project.
• Immunocompromised host such as patient receive systemic immunosuppressive drugs or systemic chemotherapy.
• Research participant or his representative refuses or requests to withdraw,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Patient receive metformin with pulmonary tuberculosis standard treatment.; Patient receive pulmonary tuberculosis standard treatment: isoniazid, rifampicin, pyrazinamide, and ethambutol in first and second month(weight adjusted dose), then in third to sixth month switch tuberculosis standard treatment to isoniazid and rifampicin(weight adjusted dose). In all 6 months, patient receive metformin (500 mg) 1 tablet simultaneously.	Drug: MetFORMIN 500 Mg Oral Tablet; studying about acid-fast bacillus sputum conversion ratio from positive to negative of pulmonary tuberculosis patients receive metformin with pulmonary tuberculosis standard treatment group in second week, second, fifth, and sixth month.
Placebo Comparator: Patient receive placebo drug with pulmonary tuberculosis standard treatment.; Patient receive pulmonary tuberculosis standard treatment: isoniazid, rifampicin, pyrazinamide, and ethambutol in first and second month(weight adjusted dose), then in third to sixth month switch tuberculosis standard treatment to isoniazid and rifampicin(weight adjusted dose). In all 6 months, patient receive placebo drug 1 tablet simultaneously.	Drug: Placebo; studying about acid-fast bacillus sputum conversion ratio from positive to negative of pulmonary tuberculosis patients receive placebo drug with pulmonary tuberculosis standard treatment group in second week, second, fifth, and sixth month.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To study about acid-fast bacillus sputum conversion ratio from positive to negative of pulmonary tuberculosis patients between metformin and placebo drug with pulmonary tuberculosis standard treatment.	patient will be collected sputum acid fast bacillus and sputum culture for tuberculosis in second week, second, fifth, sixth month.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To study about side effect such as nausea, vomit, hepatitis between patients use metformin with pulmonary tuberculosis standard treatment and patients use placebo drug with pulmonary tuberculosis standard treatment.	To compare incidence rate of side effect between patients use metformin with pulmonary tuberculosis standard treatment and patients use placebo drug with pulmonary tuberculosis standard treatment.	6 months

Collaborators and Investigators

• Sponsor: Mahidol University
• Collaborators: Ministry of Health, Thailand

Publications and helpful links

General Publications

• Singhal A, Jie L, Kumar P, Hong GS, Leow MK, Paleja B, Tsenova L, Kurepina N, Chen J, Zolezzi F, Kreiswirth B, Poidinger M, Chee C, Kaplan G, Wang YT, De Libero G. Metformin as adjunct antituberculosis therapy. Sci Transl Med. 2014 Nov 19;6(263):263ra159. doi: 10.1126/scitranslmed.3009885.
• Lee YJ, Han SK, Park JH, Lee JK, Kim DK, Chung HS, Heo EY. The effect of metformin on culture conversion in tuberculosis patients with diabetes mellitus. Korean J Intern Med. 2018 Sep;33(5):933-940. doi: 10.3904/kjim.2017.249. Epub 2018 Mar 16.
• Degner NR, Wang JY, Golub JE, Karakousis PC. Metformin Use Reverses the Increased Mortality Associated With Diabetes Mellitus During Tuberculosis Treatment. Clin Infect Dis. 2018 Jan 6;66(2):198-205. doi: 10.1093/cid/cix819.
• Yu X, Li L, Xia L, Feng X, Chen F, Cao S, Wei X. Impact of metformin on the risk and treatment outcomes of tuberculosis in diabetics: a systematic review. BMC Infect Dis. 2019 Oct 17;19(1):859. doi: 10.1186/s12879-019-4548-4.
• Lashen H. Role of metformin in the management of polycystic ovary syndrome. Ther Adv Endocrinol Metab. 2010 Jun;1(3):117-28. doi: 10.1177/2042018810380215.
• Ning HH, Le J, Wang Q, Young CA, Deng B, Gao PX, Zhang HQ, Qin SL. The effects of metformin on simple obesity: a meta-analysis. Endocrine. 2018 Dec;62(3):528-534. doi: 10.1007/s12020-018-1717-y. Epub 2018 Aug 27.
• Novita BD, Ali M, Pranoto A, Soediono EI, Mertaniasih NM. Metformin induced autophagy in diabetes mellitus - Tuberculosis co-infection patients: A case study. Indian J Tuberc. 2019 Jan;66(1):64-69. doi: 10.1016/j.ijtb.2018.04.003. Epub 2018 Apr 17.
• Vashisht R, Brahmachari SK. Metformin as a potential combination therapy with existing front-line antibiotics for Tuberculosis. J Transl Med. 2015 Mar 7;13:83. doi: 10.1186/s12967-015-0443-y.

Helpful Links

• Clinical Evaluation of Efficacy and Safety of Metformin add-on Therapy to Standard ATT in Newly Diagnosed Pulmonary Tuberculosis Patients

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2022
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): March 31, 2023

Study Registration Dates

• First Submitted: January 18, 2022
• First Submitted That Met QC Criteria: January 18, 2022
• First Posted (Actual): January 31, 2022

Study Record Updates

• Last Update Posted (Actual): February 14, 2022
• Last Update Submitted That Met QC Criteria: January 30, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Metformin; Tuberculosis
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: MURA2021/816

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No