Efficacy and Safety of Immunomodulator as an Adjunct Therapy in New Pulmonary Tuberculosis(Category I) Patients.

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Efficacy and Safety of Immunomodulator (Mycobacterium w.) as an Adjunct Therapy in Category I Pulmonary Tuberculosis and Along With Assessment of Immunological Parameters

Conditions
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Tuberculosis

Intervention / Treatment
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* Biological: Intradermal injection of Mycobacterium w


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients of either sex aged between 18 to 60 yrs. 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. Patients who are willing to give an informed consent. Exclusion Criteria Known hypersensitivity to Category I anti-TB drugs on history at the time of Screening. 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. Presence of secondary immunodeficiency states: HIV, organ transplantation, diabetes mellitus, malignancy, treatment with corticosteroids (illicited on detailed history and lab investigations). Hepatitis B and C positivity. Patients with known extrapulmonary TB and/or patients requiring surgical intervention. Currently receiving cytotoxic therapy, or have received it within the last 3 months- Ask on History. Pregnancy and lactation on history. Patients with a known seizure disorder on history. Patients with known symptomatic cardiac disease, such as arrhythmias or coronary artery disease on history. Patients with abnormal renal function (Serum creatinine more than 1.5 or proteinuria more than 2+ ) Patients with abnormal hepatic functions (bilirubin = 1.5 mg/dl; AST, ALT, SAP more than 1.5 x ULN; PT = 1.3x control) Patients with hematological abnormalities (WBC lesser than or equal to 3000/mm3; platelets less than or equal to 100,000/mm3). Seriously ill and moribund patients with complications: low lung reserve, marked tachypnoea, chronic cor pulmonale, congestive cardiac failure, BMI<15, severe hypoalbuminemia (< 2.5 g/dl). Patients unlikely to survive for less than 6 months. Patients unable to comply with the treatment regimen. 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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>In one arm the patient will receive intradermal Mycobacterium W Vaccine along with Category I ATT drugs according to RNTCP guidelines | Biological: Intradermal injection of Mycobacterium w<br>* Mw Vaccine is given as intradermal administration. Total 6 doses are given 0.2 ml at baseline and then 0.1 ml after interval of 2 weeks upto 8 weeks<br>* Other names: Immuvac;|
| Placebo Comparator: 2<br>In this Arm patient will receive Placebo along with Category I ATT drugs according to RNTCP guidelines | Biological: Intradermal injection of Mycobacterium w<br>* Mw Vaccine is given as intradermal administration. Total 6 doses are given 0.2 ml at baseline and then 0.1 ml after interval of 2 weeks upto 8 weeks<br>* Other names: Immuvac;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time of sputum conversion as well as the early sputum conversion between the two groups will be evaluated. |  | from the baseline(visit 2) | 
| The cure rate will be evaluated as the primary parameter of efficacy. |  | 6-7 month | 
| The relapse in patients of category-I pulmonary TB will be compared in both the groups. |  | at an interval of 6,12,18 and 24 months after the completion of the therapy | 
| Recording of any clinical adverse reactions for assessment of safety. |  | at anytime during the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| An additional secondary efficacy endpoint is the patient's and physicians's global assessment of the clinical cure. |  | 6-7 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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India, Pulmonary Tuberculosis, Category-I Pulmonary Tuberculosis, Immunomodulator, Mycobacterium w