TuberculosisNCT01611402
Gene Expression in HIV and Tuberculosis Co-infection
An observational study of Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: Tuberculosis (TB) infection is particularly deadly when it happens in people who are also infected with the human immunodeficiency virus (HIV). However, not much is known about how these two infections affect each other. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis
- How many people
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- 29 May 2012to 6 Apr 2016
- Phase
- Observational
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For all patients:
- Adults, age 18 or older
- TB diagnosis, ascertained as follows:
- specimen or biopsy smear, culture, or PCR positivity or
- compatible clinical presentation and imaging with strong suspicion for TB that necessitates initiation of empiric TB therapy (in which case the confirmation by culture or other laboratory means may follow enrollment, or alternatively clinical improvement in response to TB therapy may confirm the diagnosis).
- If the TB diagnosis cannot be confirmed as above (i.e. culture positive for NTM), the patient will be excluded from final analysis.
Show all 21Show fewer
- Ability and willingness of subject or legal guardian/representative to understand study requirements and give informed consent. In the event an adult subject is unable, due to illness or mental incapacity, to give informed consent, a person authorized with durable power of attorney (DPA) or legal guardian may give consent for the subject s blood to be obtained, shipped, and tested under this protocol.
- Agree to storage of study data and biologic specimens for use in future studies of immune function, tuberculosis, genetics, and/or HIV pathogenesis.
- Patients in TB mono-infected arm (Group A) would additionally be eligible if:
- HIV negative (documented seronegative within 1 month of study visit)
- Not receiving TB therapy for more than 7 days prior to study visit (Group A1) or
- Currently on TB therapy for >7 days and < 5 months (Group A2)
- Patients in TB/HIV co-infected arm (Group B) would additionally be eligible if:
- HIV positive (outside HIV testing will be accepted)
- Not receiving TB therapy for more than 7 days prior to study visit
- Untreated or ART na(SqrRoot) ve (will be accepted if they had been on ART in the past but none within the last 6 months).
- Patients in TB/HIV co-infected, treated arm (Group C) would additionally be eligible if:
- HIV positive
- Currently receiving TB therapy
- Currently receiving ART (The subset of patients without TB-IRIS will have been on antiretroviral therapy for at least 8 and not more than 12 weeks. The subset of patients with TB-IRIS will be enrolled at the time of their TB-IRIS event) with some evidence of adherence (often measured by clinical improvement, medication refills or laboratory values)
- The TB-IRIS subset of patients (15 patients at NIAID and 20 patients at SHAPHC) would also need to meet criteria for paradoxical TB-IRIS
Who cannot join
- Pregnancy or post-partum period (6 months post-partum or while breast-feeding, whichever is longer).
- Documented history of hemoglobin from most recent blood draw less than 7g/dL.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Transcriptional Signature of HIV And TB Co-Infection
Background:
- Tuberculosis (TB) infection is particularly deadly when it happens in people who are also infected with the human immunodeficiency virus (HIV). However, not much is known about how these two infections affect each other. Some people who have HIV or TB infections develop health problems after they start taking either HIV or TB medications or both. These drugs can improve the body s ability to fight infections, but sometimes this sudden improvement can make the infected person initially become sicker. Researchers want to study how these infections affect the immune system and the gene expression of people who have TB and may or may not have HIV, to see if there is a pattern of gene expression that may predict whether people starting treatment may get sicker initially.
Read more
Objectives:
- To study the gene expression and immune systems of people with TB who may or may not also have HIV.
Eligibility:
- Adults at least 18 years of age who have tuberculosis.
- Participants will be drawn from study sites in the United States and China.
Design:
- Participants will be divided into three study groups. The first group will have TB but not HIV. The second group will have both TB and HIV that have not been treated. The third group will have both TB and HIV that are currently being treated.
- All participants will have a single study visit. Blood samples will be collected at this visit. A medical history will also be collected.
- No treatment will be provided as part of this study.
Read the detailed description
Tuberculosis (TB) remains one of the deadliest infections throughout the world, particularly in the setting of HIV infection. In China, TB is a frequently diagnosed complication of HIV infection. The immunopathogenesis of TB remains unclear, and although it is known that HIV infection increases the risk of developing active TB, either through infection or reactivation of latent disease, how it does so has yet to be determined. It is also known that patients co-infected with HIV and TB and na(SqrRoot) ve to antiretroviral therapy (ART) have a particularly high risk of developing Immune Reconstitution Inflammatory Syndrome (IRIS) after ART therapy is initiated, but the immunopathogenesis of this reaction is also unclear.
The use of genomics has significantly improved the understanding of disease pathogenesis and is increasingly being used to predict responses to therapy as well. Recently, blood transcriptional signatures capable of distinguishing active and latent TB infection have been identified using highly parallelized analytical platforms capable of simultaneous survey of transcription of known genes. These signatures have hinted at a complex role for type I interferons in the development of active TB infection, but this has not yet been studied in people with HIV and TB co-infection. Further in depth studies are needed to characterize the spectrum of responses to TB/HIV co-infection, and how these responses correlate with clinical data.
We propose a cross-sectional cohort study, to be conducted in both the US and in China, to identify blood mRNA expression profiles distinguishing TB mono-infected and TB/HIV co-infected ART-na(SqrRoot) ve patients from treated patients with and without TB-IRIS. Secondary objectives will include correlating gene expression levels with clinical outcomes and soluble biomarkers. The study will comprise a test set (in China) of up to 140 patients divided among the different cohorts and a validation set (in the US) of up to 125 patients divided among the three groups Participation will involve a single study visit to consist of small volume phlebotomy (approximately 25 mL for safety labs, transcriptome analysis, lymphocyte counts, and serum and plasma storage) a urine sample and information gleaned from the clinical record entered into a coded Case Report Form (CRF). The U.S. cohort will have an additional 40 mLs of blood collected for mononuclear cells (total of approximately 65mLs).The study will exclude women who are pregnant or breast-feeding (which can be associated with immune compromise and changes in markers associated with inflammation), and persons with anemia (who may be unable to tolerate phlebotomy solely for research purposes).
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, HIV Infection, Transcriptional Signature, IRIS
- Medical subject headings
- Tuberculosis, HIV Infections
What is being measured
The primary outcome is the main question the study is designed to answer.
Identify blood mRNA expression profiles distinguishing TB onoinfectedfrom TB/HIV co-infected patients (ART-naive and ART-treated with and without TB-IRIS).
Measured: During data analysis phase
Secondary outcomes (3)
Correlate gene expression levels with clinical and laboratory variablesincluding flow cytometry and soluble biomarkers.
Measured: During data analysis phase
Quantify the tuberculosis antigen load at the beginning of anti-TB therapy by lateral flow lipo-arabinomannan assay (TB-LAM LFA) and study how the antigen burden affects the disease presentation (including radiographic findings), or transcriptio...
Measured: During data analysis phase.
Study separated cell populations (monocytes, dendritic cells, NK, T cell subsets or neurtrophils) to validate any identified transcriptional signature or to further investigate pathogen-specific responses.
Measured: During data analysis phase
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2012 (estimated)
- Study start29 May 2012
- Study completion6 Apr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Irini Sereti, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01611402
- Sponsor's protocol ID
- 120142
- Other IDs
- 12-I-0142
- Status last verified
- 6 Apr 2016
- First submitted
- 1 Jun 2012
- Last updated
- 5 Apr 2018
- Results posted
- No
Publications
Meintjes G, Rabie H, Wilkinson RJ, Cotton MF. Tuberculosis-associated immune reconstitution inflammatory syndrome and unmasking of tuberculosis by antiretroviral therapy. Clin Chest Med. 2009 Dec;30(4):797-810, x. doi: 10.1016/j.ccm.2009.08.013.
PubMed 19925968Harries AD, Zachariah R, Corbett EL, Lawn SD, Santos-Filho ET, Chimzizi R, Harrington M, Maher D, Williams BG, De Cock KM. The HIV-associated tuberculosis epidemic--when will we act? Lancet. 2010 May 29;375(9729):1906-19. doi: 10.1016/S0140-6736(10)60409-6. Epub 2010 May 18.
PubMed 20488516Houben RM, Crampin AC, Ndhlovu R, Sonnenberg P, Godfrey-Faussett P, Haas WH, Engelmann G, Lombard CJ, Wilkinson D, Bruchfeld J, Lockman S, Tappero J, Glynn JR. Human immunodeficiency virus associated tuberculosis more often due to recent infection than reactivation of latent infection. Int J Tuberc Lung Dis. 2011 Jan;15(1):24-31.
PubMed 21276292
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcriptional Signature of HIV And TB Co-Infection
- ClinicalTrials.gov ID
- NCT01611402
- Acronym / sponsor ID
- 120142
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, HIV Infection, Transcriptional Signature, IRIS
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 29 May 2012
- Study completion
- 6 Apr 2016
- First posted
- 5 Jun 2012 (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.
Background:
- Tuberculosis (TB) infection is particularly deadly when it happens in people who are also infected with the human immunodeficiency virus (HIV). However, not much is known about how these two infections affect each other. Some people who have HIV or TB infections develop health problems after they start taking either HIV or TB medications or both. These drugs can improve the body s ability to fight infections, but sometimes this sudden improvement can make the infected person initially become sicker. Researchers want to study how these infections affect the immune system and the gene expression of people who have TB and may or may not have HIV, to see if there is a pattern of gene expression that may predict whether people starting treatment may get sicker initially.
Objectives:
- To study the gene expression and immune systems of people with TB who may or may not also have HIV.
Eligibility:
- Adults at least 18 years of age who have tuberculosis.
- Participants will be drawn from study sites in the United States and China.
Design:
- Participants will be divided into three study groups. The first group will have TB but not HIV. The second group will have both TB and HIV that have not been treated. The third group will have both TB and HIV that are currently being treated.
- All participants will have a single study visit. Blood samples will be collected at this visit. A medical history will also be collected.
- No treatment will be provided as part of this study.
Detailed description
Tuberculosis (TB) remains one of the deadliest infections throughout the world, particularly in the setting of HIV infection. In China, TB is a frequently diagnosed complication of HIV infection. The immunopathogenesis of TB remains unclear, and although it is known that HIV infection increases the risk of developing active TB, either through infection or reactivation of latent disease, how it does so has yet to be determined. It is also known that patients co-infected with HIV and TB and na(SqrRoot) ve to antiretroviral therapy (ART) have a particularly high risk of developing Immune Reconstitution Inflammatory Syndrome (IRIS) after ART therapy is initiated, but the immunopathogenesis of this reaction is also unclear.
The use of genomics has significantly improved the understanding of disease pathogenesis and is increasingly being used to predict responses to therapy as well. Recently, blood transcriptional signatures capable of distinguishing active and latent TB infection have been identified using highly parallelized analytical platforms capable of simultaneous survey of transcription of known genes. These signatures have hinted at a complex role for type I interferons in the development of active TB infection, but this has not yet been studied in people with HIV and TB co-infection. Further in depth studies are needed to characterize the spectrum of responses to TB/HIV co-infection, and how these responses correlate with clinical data.
We propose a cross-sectional cohort study, to be conducted in both the US and in China, to identify blood mRNA expression profiles distinguishing TB mono-infected and TB/HIV co-infected ART-na(SqrRoot) ve patients from treated patients with and without TB-IRIS. Secondary objectives will include correlating gene expression levels with clinical outcomes and soluble biomarkers. The study will comprise a test set (in China) of up to 140 patients divided among the different cohorts and a validation set (in the US) of up to 125 patients divided among the three groups Participation will involve a single study visit to consist of small volume phlebotomy (approximately 25 mL for safety labs, transcriptome analysis, lymphocyte counts, and serum and plasma storage) a urine sample and information gleaned from the clinical record entered into a coded Case Report Form (CRF). The U.S. cohort will have an additional 40 mLs of blood collected for mononuclear cells (total of approximately 65mLs).The study will exclude women who are pregnant or breast-feeding (which can be associated with immune compromise and changes in markers associated with inflammation), and persons with anemia (who may be unable to tolerate phlebotomy solely for research purposes).
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Adults, age 18 or older
- TB diagnosis, ascertained as follows:
- If the TB diagnosis cannot be confirmed as above (i.e. culture positive for NTM), the patient will be excluded from final analysis.
- Ability and willingness of subject or legal guardian/representative to understand study requirements and give informed consent. In the event an adult subject is unable, due to illness or mental incapacity, to give informed consent, a person authorized with durable power of attorney (DPA) or legal guardian may give consent for the subject s blood to be obtained, shipped, and tested under this protocol.
- Agree to storage of study data and biologic specimens for use in future studies of immune function, tuberculosis, genetics, and/or HIV pathogenesis.
Key exclusion criteria (2 listed)
- Pregnancy or post-partum period (6 months post-partum or while breast-feeding, whichever is longer).
- Documented history of hemoglobin from most recent blood draw less than 7g/dL.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Identify blood mRNA expression profiles distinguishing TB onoinfectedfrom TB/HIV co-infected patients (ART-naive and ART-treated with and without TB-IRIS).
Time frame: During data analysis phase
3 secondary outcomes
Correlate gene expression levels with clinical and laboratory variablesincluding flow cytometry and soluble biomarkers.
Time frame: During data analysis phase
Quantify the tuberculosis antigen load at the beginning of anti-TB therapy by lateral flow lipo-arabinomannan assay (TB-LAM LFA) and study how the antigen burden affects the disease presentation (including radiographic findings), or transcriptio...
Time frame: During data analysis phase.
Study separated cell populations (monocytes, dendritic cells, NK, T cell subsets or neurtrophils) to validate any identified transcriptional signature or to further investigate pathogen-specific responses.
Time frame: During data analysis phase
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 5 Apr 2018.
- Background: PubMed 19925968Meintjes G, Rabie H, Wilkinson RJ, Cotton MF. Tuberculosis-associated immune reconstitution inflammatory syndrome and unmasking of tuberculosis by antiretroviral therapy. Clin Chest Med. 2009 Dec;30(4):797-810, x. doi: 10.1016/j.ccm.2009.08.013.
- Background: PubMed 20488516Harries AD, Zachariah R, Corbett EL, Lawn SD, Santos-Filho ET, Chimzizi R, Harrington M, Maher D, Williams BG, De Cock KM. The HIV-associated tuberculosis epidemic--when will we act? Lancet. 2010 May 29;375(9729):1906-19. doi: 10.1016/S0140-6736(10)60409-6. Epub 2010 May 18.
- Background: PubMed 21276292Houben RM, Crampin AC, Ndhlovu R, Sonnenberg P, Godfrey-Faussett P, Haas WH, Engelmann G, Lombard CJ, Wilkinson D, Bruchfeld J, Lockman S, Tappero J, Glynn JR. Human immunodeficiency virus associated tuberculosis more often due to recent infection than reactivation of latent infection. Int J Tuberc Lung Dis. 2011 Jan;15(1):24-31.
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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.
Irini Sereti, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
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 21 inclusion and 2 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 5 Apr 2018. 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 United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Identify blood mRNA expression profiles distinguishing TB onoinfectedfrom TB/HIV co-infected patients (ART-naive and ART-treated with and without TB-IRIS). (time frame: During data analysis phase). 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 NCT01611402, which also lists 3 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 5 Apr 2018.