Efficacy and Safety of Immunomodulator as an Adjunct Therapy in New Pulmonary Tuberculosis(Category I) Patients.
Efficacy and Safety of Immunomodulator as an Adjunct Therapy in New Pulmonary Tuberculosis(Category I) Patients.
The purpose of the study is to evaluate the efficacy and safety of Mycobacterium w in new
 lung tuberculosis patients. Mycobacterium w is a strain of bacterium which is being used as
 vaccine and adjunct drug against leprosy. This agent has also been found to be useful in the
 treatment of lung tuberculosis in limited number of patients.

 We are conducting this study in category-I patients( As per World Health Organization,Geneva
 classification of tuberculosis) having lung tuberculosis to see the efficacy and also to see
 any change in the immunological parameters.
Mycobacterium w is a recently introduced immunomodulator ,which has been found to be useful
 in rapid killing of Mycobacterium leprae. It improves clearance of Mycobacterium leprae from
 body and is thereby useful in reducing duration of therapy significantly for multibacillary
 leprosy. Mycobacterium w shares antigens with Mycobacterium leprae as well as Mycobacterium
 tuberculosis. Mycobacterium w is also found to be useful in prevention of tuberculosis in
 experimental animals. Previous studies for efficacy of Mycobacterium w as immunomodulator in
 pulmonary tuberculosis patients have shown faster sputum conversion rates in patients given
 Mycobacterium w as an adjuvant therapy along with standard anti-tuberculosis treatment. It
 has faster and remarkable sputum converting capacity. Similar studies conducted in pulmonary
 TB category -II [Re-treatment as per Revised National Tuberculosis Control Programme (RNTCP),
 Govt. of India] patients have shown improved cure rates.

 Mycobacterium w is commercially available under the brand name of "Immuvac" injection in 0.5
 ml multi-dose vials approved for use as immunomodulator against Mycobacterium leprae in
 patients with leprosy. Each vial has 500 million heat-killed bacilli in a buffered solution.
 It is manufactured by Cadila Pharmaceuticals Ltd.; Ahmedabad, Gujarat-382 210, India. In this
 clinical trial one dose consists of 0.1 ml given as intradermal injection, which contains 100
 million bacilli. A total of 6 doses are given during the Intensive Phase(as per
 RNTCP,Ministry of Health and Family Welfare,Govt.of India) of treatment. Two injections on
 both upper arms on day-0 and subsequently one injection on days 14,28,42 and 56. No
 injections are given during the Continuation Phase(as per RNTCP,Ministry of Health and Family
 Welfare,Govt.of India)of treatment.

 As of now it is not commercially available for therapeutic use in TB patients as
 immunomodulator.Therefore we are investigating Mycobacterium w for its efficacy in TB
 patients in a "double-blind placebo-controlled randomized clinical control trial" fashion. We
 are conducting this trial in Category-I pulmonary TB Patients(as per RNTCP,Ministry of Health
 and Family Welfare,Govt.of India),and are assessing the outcome in the form of clinical
 improvement,sputum conversion and immunological parameters. This is a multi-centric trial
 sponsored by the Department of Biotechnology, Ministry of Science and Technology, Govt. of
 India and Cadila Pharmaceuticals Ltd., India.
Inclusion Criteria

 1. Patients of either sex aged between 18 to 60 yrs.

 2. Newly diagnosed sputum positive pulmonary TB cases with at least 2 sputum samples that
 are positive on sputum microscopy (Negative, Scanty, Scanty may be enrolled.

 3. Patients who are willing to give an informed consent.

 Exclusion Criteria

 1. Known hypersensitivity to Category I anti-TB drugs on history at the time of
 Screening.

 2. Known history of DR-TB (includes MDR-TB and XDR-TB) at the time of screening. Patients
 with Mtb isolate resistant to one or more drugs are to be excluded.

 3. Presence of secondary immunodeficiency states: HIV, organ transplantation, diabetes
 mellitus, malignancy, treatment with corticosteroids (illicited on detailed history
 and lab investigations).

 4. Hepatitis B and C positivity.

 5. Patients with known extrapulmonary TB and/or patients requiring surgical intervention.

 6. Currently receiving cytotoxic therapy, or have received it within the last 3 months-
 Ask on History.

 7. Pregnancy and lactation on history.

 8. Patients with a known seizure disorder on history.

 9. Patients with known symptomatic cardiac disease, such as arrhythmias or coronary
 artery disease on history.

 10. Patients with abnormal renal function (Serum creatinine more than 1.5 or proteinuria
 more than 2+ )

 11. Patients with abnormal hepatic functions (bilirubin = 1.5 mg/dl; AST, ALT, SAP more
 than 1.5 x ULN; PT = 1.3x control)

 12. Patients with hematological abnormalities (WBC lesser than or equal to 3000/mm3;
 platelets less than or equal to 100,000/mm3).

 13. Seriously ill and moribund patients with complications:

 1. low lung reserve, marked tachypnoea, chronic cor pulmonale, congestive cardiac
 failure, BMI<15,

 2. severe hypoalbuminemia (< 2.5 g/dl).

 14. Patients unlikely to survive for less than 6 months.

 15. Patients unable to comply with the treatment regimen.

 16. Patients with history of alcohol or drug abuse- to be asked for on history and
 assessed using the CAGE Questions. The patient should be asked four questions in the
 following manner. A positive response to any of the following questions will be
 considered an exclusion criterion.

 i. Have you ever felt a need to CUT DOWN your drinking?

 ii. Have you ever felt ANGRY when confronted about the amount of alcohol you drink?

 iii. Have you ever felt GUILTY when confronted about the amount of alcohol you drink?

 iv. Have you ever felt the need to have a drink first thing in the morning? (EYE
 OPENER).