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

NCT ID: NCT00341328

Last Updated: 2013-04-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-03-31

Study Completion Date

2012-03-31

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.

Conditions

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Tuberculosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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1

In one arm the patient will receive intradermal Mycobacterium W Vaccine along with Category I ATT drugs according to RNTCP guidelines

Group Type EXPERIMENTAL

Intradermal injection of Mycobacterium w

Intervention Type BIOLOGICAL

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

2

In this Arm patient will receive Placebo along with Category I ATT drugs according to RNTCP guidelines

Group Type PLACEBO_COMPARATOR

Intradermal injection of Mycobacterium w

Intervention Type BIOLOGICAL

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

Interventions

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Intradermal injection of Mycobacterium w

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

Intervention Type BIOLOGICAL

Other Intervention Names

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Immuvac

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ministry of Science and Technology, India

OTHER_GOV

Sponsor Role lead

Responsible Party

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SK Sharma

Professor and Head

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Surendra K Sharma, MD, Ph.D.

Role: STUDY_CHAIR

Professor and Head,Department of Medicine, AIIMS, New Delhi-110029

Bindu Dey, Ph.D.

Role: STUDY_DIRECTOR

Department of Biotechnology, MST, GOI

Locations

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All India Institute of Medical Sciences

New Delhi, National Capital Territory of Delhi, India

Site Status

Central JALMA Institute of Leprosy and Other Mycobacterial Diseases

Agra, , India

Site Status

Countries

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India

References

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Patel N, Trapathi SB. Improved cure rates in pulmonary tuberculosis category II (retreatment) with mycobacterium w. J Indian Med Assoc. 2003 Nov;101(11):680, 682.

Reference Type BACKGROUND
PMID: 15198421 (View on PubMed)

Patel N, Deshpande MM, Shah M. Effect of an immunomodulator containing Mycobacterium w on sputum conversion in pulmonary tuberculosis. J Indian Med Assoc. 2002 Mar;100(3):191-3.

Reference Type BACKGROUND
PMID: 12408283 (View on PubMed)

Katoch K, Katoch VM, Natrajan M, Bhatia AS, Sreevatsa, Gupta UD, Sharma VD, Shivannavar CT, Patil MA, Bharadwaj VP. Treatment of bacilliferous BL/LL cases with combined chemotherapy and immunotherapy. Int J Lepr Other Mycobact Dis. 1995 Jun;63(2):202-12.

Reference Type BACKGROUND
PMID: 7602215 (View on PubMed)

Sharma P, Mukherjee R, Talwar GP, Sarathchandra KG, Walia R, Parida SK, Pandey RM, Rani R, Kar H, Mukherjee A, Katoch K, Benara SK, Singh T, Singh P. Immunoprophylactic effects of the anti-leprosy Mw vaccine in household contacts of leprosy patients: clinical field trials with a follow up of 8-10 years. Lepr Rev. 2005 Jun;76(2):127-43.

Reference Type BACKGROUND
PMID: 16038246 (View on PubMed)

Sharma P, Kar HK, Misra RS, Mukherjee A, Kaur H, Mukherjee R, Rani R. Disabilities in multibacillary leprosy following multidrug therapy with and without immunotherapy with Mycobacterium w antileprosy vaccine. Int J Lepr Other Mycobact Dis. 1999 Sep;67(3):250-8.

Reference Type BACKGROUND
PMID: 10575404 (View on PubMed)

Sharma P, Kar HK, Misra RS, Mukherjee A, Kaur H, Mukherjee R, Rani R. Reactional states and neuritis in multibacillary leprosy patients following MDT with/without immunotherapy with Mycobacterium w antileprosy vaccine. Lepr Rev. 2000 Jun;71(2):193-205. doi: 10.5935/0305-7518.20000021.

Reference Type BACKGROUND
PMID: 10920614 (View on PubMed)

Sharma P, Misra RS, Kar HK, Mukherjee A, Poricha D, Kaur H, Mukherjee R, Rani R. Mycobacterium w vaccine, a useful adjuvant to multidrug therapy in multibacillary leprosy: a report on hospital based immunotherapeutic clinical trials with a follow-up of 1-7 years after treatment. Lepr Rev. 2000 Jun;71(2):179-92. doi: 10.5935/0305-7518.20000020.

Reference Type BACKGROUND
PMID: 10920613 (View on PubMed)

Sharma P, Kar HK, Misra RS, Mukherjee A, Kaur H, Mukherjee R, Rani R. Induction of lepromin positivity following immuno-chemotherapy with Mycobacterium w vaccine and multidrug therapy and its impact on bacteriological clearance in multibacillary leprosy: report on a hospital-based clinical trial with the candidate antileprosy vaccine. Int J Lepr Other Mycobact Dis. 1999 Sep;67(3):259-69.

Reference Type BACKGROUND
PMID: 10575405 (View on PubMed)

Sharma SK, Mitra DK, Balamurugan A, Pandey RM, Mehra NK. Cytokine polarization in miliary and pleural tuberculosis. J Clin Immunol. 2002 Nov;22(6):345-52. doi: 10.1023/a:1020604331886.

Reference Type BACKGROUND
PMID: 12462334 (View on PubMed)

Khatri GR, Frieden TR. Controlling tuberculosis in India. N Engl J Med. 2002 Oct 31;347(18):1420-5. doi: 10.1056/NEJMsa020098.

Reference Type BACKGROUND
PMID: 12409545 (View on PubMed)

Other Identifiers

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BT/PR7894/Med/14/1175/2006

Identifier Type: OTHER

Identifier Source: secondary_id

CR-01C-1/2003-10

Identifier Type: -

Identifier Source: org_study_id

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