TuberculosisPhase 2/3NCT00052195
Investigational Vaccine for the Prevention of Disseminated Tuberculosis in HIV Infected People
A Phase 2/3 study testing SRL-172 in people with Tuberculosis and HIV Infections, run by Dartmouth-Hitchcock Medical Center at 1 site in Tanzania.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis, HIV Infections
- What is being tested?
- SRL-172
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,975 participants
- Where
- 1 siteTanzania
- Study dates
- Sep 2001to May 2009
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- HIV infection
- CD4 count more than 200 cells/mm3
- BCG scar
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: DARDAR Health Project (Disseminated Tuberculosis and HIV Infection)
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.
Read the 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.
- Conditions
- Tuberculosis, HIV Infections
- Being tested
- SRL-172
- Keywords
- Mycobacterium vaccae, BCG, Disseminated tuberculosis, SRL-172, DAR-901
- Medical subject headings
- Tuberculosis, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SRL-172Biological
5 doses of 0.1mL vaccine or placebo given intradermally over 12-months
| Study group | Role | What they receive |
|---|---|---|
| B | Placebo comparator | Not described Receives: Biological: SRL-172 |
| A | Experimental | Not described Receives: Biological: SRL-172 |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety and efficacy of a prime-boost immunization strategy for the prevention of HIV-associated dTB and pTB
Measured: every six months
Secondary outcomes (1)
Risk factors for HIV-associated dTB and relative contributions of primary infection, reinfection, and reactivation in its pathogenesis
Measured: every six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startSep 2001
- Primary completionDec 2008
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by Dartmouth-Hitchcock Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,975 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, C. Fordham von Reyn, Dartmouth-Hitchcock Medical Center
- Investigators
- C. Fordham F von Reyn, MD, Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00052195
- Sponsor's protocol ID
- 1R01AI045407-01A2
- Other IDs
- 1R01AI045407-01A2, 3R01AI045407-02S1, 5R01AI045407-03, U01AI045407-06, U01AI045407-07, U01AI045407-08
- Status last verified
- Feb 2016
- First submitted
- 24 Jan 2003
- Last updated
- 19 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
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. doi: 10.1086/429825. Epub 2005 Apr 12.
PubMed 15844073von 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.
PubMed 20118767Lahey 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.
PubMed 20875492Lahey 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.
PubMed 23908490Lahey 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.
PubMed 22972862Lahey 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.
PubMed 21799772von 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.
PubMed 21740673Lahey 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.
PubMed 20812851Lahey 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.
PubMed 19236695Munseri 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.
PubMed 18713501
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DARDAR Health Project (Disseminated Tuberculosis and HIV Infection)
- ClinicalTrials.gov ID
- NCT00052195
- Acronym / sponsor ID
- 1R01AI045407-01A2
- Conditions
- Tuberculosis, HIV Infections
- Keywords
- Mycobacterium vaccae, BCG, Disseminated tuberculosis, SRL-172, DAR-901
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,975 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Sep 2001
- Primary completion
- Dec 2008 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| B | Placebo comparator | Biological: SRL-172 |
| A | Experimental | Biological: SRL-172 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- HIV infection
- CD4 count more than 200 cells/mm3
- BCG scar
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SRL-1725 doses of 0.1mL vaccine or placebo given intradermally over 12-months | Biological | A, B |
Primary outcome
safety and efficacy of a prime-boost immunization strategy for the prevention of HIV-associated dTB and pTB
Time frame: every six months
1 secondary outcome
Risk factors for HIV-associated dTB and relative contributions of primary infection, reinfection, and reactivation in its pathogenesis
Time frame: every six months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2016.
- Results publication: PubMed 15844073Mtei 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.
- Results publication: PubMed 20118767von 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.
- Results publication: PubMed 20875492Lahey 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.
- Derived from this study: PubMed 23908490Lahey 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.
- Derived from this study: PubMed 22972862Lahey 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.
- Derived from this study: PubMed 21799772Lahey 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.
- Derived from this study: PubMed 21740673von 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.
- Derived from this study: PubMed 20812851Lahey 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.
- Derived from this study: PubMed 19236695Lahey 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.
- Derived from this study: PubMed 18713501Munseri 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
C. Fordham F von Reyn, MD principal investigator
Dartmouth-Hitchcock Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing SRL-172 in people with Tuberculosis and HIV Infections, run by Dartmouth-Hitchcock Medical Center at 1 site in Tanzania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety and efficacy of a prime-boost immunization strategy for the prevention of HIV-associated dTB and pTB (time frame: every six months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00052195, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2016.