Investigational Vaccine for the Prevention of Disseminated Tuberculosis in HIV Infected People

NCT ID: NCT00052195

Last Updated: 2016-02-19

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

PHASE2/PHASE3

Total Enrollment

1975 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-09-30

Study Completion Date

2009-05-31

Brief Summary

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A significant number of HIV infected patients in Africa also have disseminated tuberculosis (infection throughout multiple organs). This type of tuberculosis is a significant cause of mortality in these patients. The purpose of this study is to evaluate the safety and effectiveness of a vaccine designed to prevent disseminated tuberculosis.

Detailed Description

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Disseminated infection with Mycobacterium tuberculosis (dMTB) has been documented in 10% to 25% of patients with HIV infection in Africa. Unlike pulmonary tuberculosis (pMTB), most cases of dMTB are not recognized and death ensues rapidly. Therefore, dMTB may be a more important cause of HIV-associated mortality than pMTB in developing countries. Mycobacterium vaccae (MV) is an investigational vaccine prepared by heat inactivation of a nontuberculous mycobacteria. MV immunization may reduce the risk of HIV-associated dMTB. The purpose of this study is to define risk factors for HIV-associated dMTB and to assess the safety and effectiveness of an MV vaccine for the prevention of HIV-associated pulmonary and disseminated tuberculosis.

HIV positive patients with prior BCG immunization and HIV negative controls will be entered in a 5-year study in Tanzania. Participants will be randomized to receive a 5-dose series of MV or placebo over 12 months, with a repeat skin test at Month 14. Baseline evaluation will include medical history, chest x-ray, skin tests with purified protein derivative (PPD), and blood tests to evaluate interferon-gamma production. Participants with PPD reactions greater than or equal to 5 mm will receive 6 months of prophylaxis with isoniazid. Participants will be followed every 3 months for 3 to 5 years to assess new pMTB (microbiologic or clinical diagnosis) or dMTB (microbiologic diagnosis). Potential risk factors for dMTB will also be assessed.

Conditions

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Tuberculosis HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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B

Group Type PLACEBO_COMPARATOR

SRL-172

Intervention Type BIOLOGICAL

5 doses of 0.1mL vaccine or placebo given intradermally over 12-months

A

Group Type EXPERIMENTAL

SRL-172

Intervention Type BIOLOGICAL

5 doses of 0.1mL vaccine or placebo given intradermally over 12-months

Interventions

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SRL-172

5 doses of 0.1mL vaccine or placebo given intradermally over 12-months

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* HIV infection
* CD4 count more than 200 cells/mm3
* BCG scar

Exclusion Criteria

* Active tuberculosis. Patients will be deferred from study enrollment until they show no signs of active disease.
* Serious underlying disease (e.g., congestive heart failure, advanced cancer)
* Life expectancy of less than 2 years
* Pregnancy. Women who are pregnant may be eligible for the study after they give birth.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role lead

Responsible Party

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C. Fordham von Reyn

Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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C. Fordham F von Reyn, MD

Role: PRINCIPAL_INVESTIGATOR

Dartmouth-Hitchcock Medical Center

Locations

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Muhimbili University College of Health Sciences

Dar es Salaam, , Tanzania

Site Status

Countries

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Tanzania

References

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Mtei L, Matee M, Herfort O, Bakari M, Horsburgh CR, Waddell R, Cole BF, Vuola JM, Tvaroha S, Kreiswirth B, Pallangyo K, von Reyn CF. High rates of clinical and subclinical tuberculosis among HIV-infected ambulatory subjects in Tanzania. Clin Infect Dis. 2005 May 15;40(10):1500-7. doi: 10.1086/429825. Epub 2005 Apr 12.

Reference Type RESULT
PMID: 15844073 (View on PubMed)

von Reyn CF, Mtei L, Arbeit RD, Waddell R, Cole B, Mackenzie T, Matee M, Bakari M, Tvaroha S, Adams LV, Horsburgh CR, Pallangyo K; DarDar Study Group. Prevention of tuberculosis in Bacille Calmette-Guerin-primed, HIV-infected adults boosted with an inactivated whole-cell mycobacterial vaccine. AIDS. 2010 Mar 13;24(5):675-85. doi: 10.1097/QAD.0b013e3283350f1b.

Reference Type RESULT
PMID: 20118767 (View on PubMed)

Lahey T, Arbeit RD, Bakari M, Horsburgh CR, Matee M, Waddell R, Mtei L, Vuola JM, Pallangyo K, von Reyn CF. Immunogenicity of a protective whole cell mycobacterial vaccine in HIV-infected adults: a phase III study in Tanzania. Vaccine. 2010 Nov 10;28(48):7652-8. doi: 10.1016/j.vaccine.2010.09.041. Epub 2010 Sep 25.

Reference Type RESULT
PMID: 20875492 (View on PubMed)

Lahey T, Czechura T, Crabtree S, Arbeit RD, Matee M, Horsburgh CR, MacKenzie T, Bakari M, Pallangyo K, von Reyn CF. Greater preexisting interferon gamma responses to mycobacterial antigens and lower bacillary load during HIV-associated tuberculosis. J Infect Dis. 2013 Nov 15;208(10):1629-33. doi: 10.1093/infdis/jit396. Epub 2013 Aug 1.

Reference Type DERIVED
PMID: 23908490 (View on PubMed)

Lahey T, Mackenzie T, Arbeit RD, Bakari M, Mtei L, Matee M, Maro I, Horsburgh CR, Pallangyo K, von Reyn CF. Recurrent tuberculosis risk among HIV-infected adults in Tanzania with prior active tuberculosis. Clin Infect Dis. 2013 Jan;56(1):151-8. doi: 10.1093/cid/cis798. Epub 2012 Sep 12.

Reference Type DERIVED
PMID: 22972862 (View on PubMed)

Lahey T, Mitchell BK, Arbeit RD, Sheth S, Matee M, Horsburgh CR, MacKenzie T, Mtei L, Bakari M, Vuola JM, Pallangyo K, von Reyn CF. Polyantigenic interferon-gamma responses are associated with protection from TB among HIV-infected adults with childhood BCG immunization. PLoS One. 2011;6(7):e22074. doi: 10.1371/journal.pone.0022074. Epub 2011 Jul 20.

Reference Type DERIVED
PMID: 21799772 (View on PubMed)

von Reyn CF, Kimambo S, Mtei L, Arbeit RD, Maro I, Bakari M, Matee M, Lahey T, Adams LV, Black W, Mackenzie T, Lyimo J, Tvaroha S, Waddell R, Kreiswirth B, Horsburgh CR, Pallangyo K. Disseminated tuberculosis in human immunodeficiency virus infection: ineffective immunity, polyclonal disease and high mortality. Int J Tuberc Lung Dis. 2011 Aug;15(8):1087-92. doi: 10.5588/ijtld.10.0517.

Reference Type DERIVED
PMID: 21740673 (View on PubMed)

Lahey T, Sheth S, Matee M, Arbeit R, Horsburgh CR, Mtei L, Mackenzie T, Bakari M, Vuola JM, Pallangyo K, von Reyn CF. Interferon gamma responses to mycobacterial antigens protect against subsequent HIV-associated tuberculosis. J Infect Dis. 2010 Oct 15;202(8):1265-72. doi: 10.1086/656332.

Reference Type DERIVED
PMID: 20812851 (View on PubMed)

Lahey T, Matee M, Mtei L, Bakari M, Pallangyo K, von Reyn CF. Lymphocyte proliferation to mycobacterial antigens is detectable across a spectrum of HIV-associated tuberculosis. BMC Infect Dis. 2009 Feb 23;9:21. doi: 10.1186/1471-2334-9-21.

Reference Type DERIVED
PMID: 19236695 (View on PubMed)

Munseri PJ, Talbot EA, Mtei L, Fordham von Reyn C. Completion of isoniazid preventive therapy among HIV-infected patients in Tanzania. Int J Tuberc Lung Dis. 2008 Sep;12(9):1037-41.

Reference Type DERIVED
PMID: 18713501 (View on PubMed)

Other Identifiers

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1R01AI045407-01A2

Identifier Type: NIH

Identifier Source: secondary_id

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3R01AI045407-02S1

Identifier Type: NIH

Identifier Source: secondary_id

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5R01AI045407-03

Identifier Type: NIH

Identifier Source: secondary_id

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U01AI045407-06

Identifier Type: NIH

Identifier Source: secondary_id

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U01AI045407-07

Identifier Type: NIH

Identifier Source: secondary_id

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U01AI045407-08

Identifier Type: NIH

Identifier Source: secondary_id

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1R01AI045407-01A2

Identifier Type: NIH

Identifier Source: org_study_id

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