Investigational Vaccine for the Prevention of Disseminated Tuberculosis in HIV Infected People - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00052195

Purpose

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.

Condition	Intervention	Phase
Tuberculosis HIV Infections	Biological: Mycobacterium vaccae	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	DARDAR Health Project (Disseminated Tuberculosis and HIV Infection)

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS Mycobacterial Infections Tuberculosis

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

safety and efficacy of a prime-boost immunization strategy for the prevention of HIV-associated dTB and pTB [ Time Frame: every six months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Risk factors for HIV-associated dTB and relative contributions of primary infection, reinfection, and reactivation in its pathogenesis [ Time Frame: every six months ] [ Designated as safety issue: No ]

Enrollment:	1975
Study Start Date:	September 2001
Estimated Study Completion Date:	May 2009
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: B	Biological: Mycobacterium vaccae 5 doses of 0.1mL vaccine or placebo given intradermally over 12-months
Experimental: A	Biological: Mycobacterium vaccae 5 doses of 0.1mL vaccine or placebo given intradermally over 12-months

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00052195

Locations

Tanzania
Muhimbili University College of Health Sciences
Dar es Salaam, Tanzania

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Principal Investigator:

C. Fordham F von Reyn, MD

Dartmouth-Hitchcock Medical Center

More Information

Publications:

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. Epub 2005 Apr 12.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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. Epub 2010 Sep 25.

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

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-Guérin-primed, HIV-infected adults boosted with an inactivated whole-cell mycobacterial vaccine. AIDS. 2010 Mar 13;24(5):675-85.

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.

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.

Responsible Party:	C. Fordham von Reyn, Professor of Medicine, Dartmouth Medical School
ClinicalTrials.gov Identifier:	NCT00052195 History of Changes
Other Study ID Numbers:	1R01AI45407-01A2, 3R01AI045407-02S1, 5R01AI045407-03, U01 AI045407-06, U01 AI045407-07, U01 AI045407-08
Study First Received:	January 24, 2003
Last Updated:	May 28, 2008
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Mycobacterium vaccae
BCG
Disseminated tuberculosis

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Tuberculosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral

Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on February 09, 2012