Mycobacterium InfectionsNCT01547884
Effect of Filarial Infection on Immune Responses in Latent Tuberculosis
An observational study of Mycobacterium Infections and Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in 2 countries.
Trial summary
Background: Lymphatic filariasis is an infection that is caused by small, thread-like worms. It is spread by mosquitoes, and causes fever, chills, and headaches. If untreated, it can also cause elephantiasis, a condition that leads to swelling of the arms, legs, breasts, and scrotum. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Mycobacterium Infections, Tuberculosis, Filariasis
- How many people
- 4,268 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Jan 2013to 7 Aug 2020
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The screening will be a community-based study in South India. Study participants will be recruited from villages in the Kancheepuram District, where approximately 6% of the population tests positive for circulating filarial antigens [31]. PPD skin test reactivity in this population is virtually 100% to PPD-B (battery) and 60% to 70% to PPD-S (standard) by age 24, and the incidence of active TB is about 4 per 1000 individuals [31]. While the rate of positivity of the tuberculin skin test to the 2TU PPD test is not known, significant deviation in the percent positivity from skin tests using 1TU is not expected based on findings reported elsewhere [32]. However, we are revising the @@@screening sample number on the basis of preliminary data from the current study that shows that the prevalence of latent TB in this population is around 25% and filariasis is around 1%. In addition, preliminary data from these areas show that the prevalence of Stronglyloides infection is around 10%.
Who may be able to join
None listed.
Who cannot join
- Pregnancy: Pregnant and lactating women will be excluded from the study because the safety of DEC or ivermectin has not been adequately evaluated during pregnancy or lactation, while albendazole is a Category C drug found to be teratogenic in animals, and it poses a potential risk during breastfeeding.
- EXCLUSION OF CHILDREN: Children (<18 years of age) will not be included in this study due to the fact the prevalence of filarial and strongyloides infection in children has been found to be very low in South India.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
National Institute of Allergy and Infectious Diseases (NIAID), 9000 Rockville Pi
Bethesda, Maryland, 20892
About this study
Official title: Effect of Filarial Infection on Antigen-Specific Immune Responses in Latent Tuberculosis
Background:
- Lymphatic filariasis is an infection that is caused by small, thread-like worms. It is spread by mosquitoes, and causes fever, chills, and headaches. If untreated, it can also cause elephantiasis, a condition that leads to swelling of the arms, legs, breasts, and scrotum. Treatment can eliminate the worms from the blood and reduce the risk of developing elephantiasis. Researchers want to study people with latent tuberculosis (TB) who may or may not be infected with filariasis. This study will look at the way that people with latent TB fight infection with these worms.
Read more
Objectives:
- To study how the immune systems of people with latent TB react to filarial infection.
Eligibility:
- Individuals between 18 and 65 years of age who have latent TB and may or may not have filarial infection.
Design:
- Participants will be screened with a physical exam and medical history. They will provide a blood and stool sample to test for infection.
- Participants who do not have lymphatic filariasis but have another kind of intestinal worm will be treated for the parasite. This will be their last study visit.
- Participants who have latent TB and lymphatic filariasis will be treated with the standard treatment for the disease. They will come back for a second visit 6 months later, and will provide another blood sample.
Read the detailed description
Tissue-invasive helminth parasites infect close to 500 million people worldwide and are associated with strong T helper (Th)2 responses and regulatory networks that downregulate potentially protective Th1 responses. The two common tissue invasive helminth parasites are Wuchereria bancrofti, that causes lymphatic filariasis and Strongyloides stercoralis, that causes stronyloidiasis. Previous studies have shown that the intestinal helminth coinfection is accompanied by lowered in vitro production of interferon-gamma and elevated production of interleukin 10 in individuals with active pulmonary tuberculosis (TB). Our team has recently shown that co-existent filarial TB infections down-regulate Th1 and Th17 responses, which are necessary for protection against active TB.
The current study will compare immune responses to mycobacterial antigens in individuals with latent tuberculosis (LTBI+) and concomitant helminth infection (Hel+), including those with filarial (Fil+) and strongyloides (STR+) infection versus those with LTBI+ without concomitant helminth infection (Hel-). Immune responses to mycobacterial antigens from co-infected individuals will also be evaluated before and after treatment for helminth infection. Individuals (n=4000) will sign a screening consent prior to undergoing any study procedures. Every participant will have their medical history collected and will undergo a physical exam and a tuberculin 2TU purified protein derivative (PPD) skin test; women of childbearing potential will also undergo a urine pregnancy test, and those with positive test results will be excluded from the study. Individuals with positive PPD skin test results (> or = 5 mm) and no symptoms of active TB will have their blood drawn (5 mL) as part of the screening procedures to confirm LTBI+ status, evaluate circulating filarial antigenemia, determine Strongyloides status by ELISA, measure hematocrit levels, and for storage of serum samples; those with PPD skin test results less than or equal to 5 mm will be excluded from the study. Individuals with positive symptoms for TB will also be excluded from the study, but sputum will be collected from them, and those with positive smears will be referred for treatment. Individuals will be matched for age, gender, and geographic location, and they will be assigned to one of two groups, LTBI+ Hel+ (n=100) or LTBI+ Hel- (n=100).
Within 3 months of screening, individuals will be asked to sign an on-study consent and will undergo a second blood draw (10 mL) for immunological investigations and storage of serum samples; women of childbearing potential will undergo a repeat urine pregnancy test, and those with positive test results will be excluded from further study. Stool samples will also be collected for microscopic evaluation of ova and parasites. LTBI+ Fil+ individuals will be treated with a single standard dose of albendazole (400 mg) and single standard dose of diethylcarbamazine citrate (300 mg), which are available through the National Programme for the Elimination of Lymphatic Filariasis in India. LTBI+ STR+ individuals will be treated with a single standard dose of ivermectin (12mg) and a single standard dose of albendazole (400mg). These individuals will be asked to return 6 months after treatment to undergo a third blood draw (10 mL) for additional immunological investigations and storage of serum samples. LTBI+ Hel-individuals who test positive for other intestinal helminth infection will be treated with a single standard dose of albendazole (400 mg).
- Keywords
- T Cells, Immune Responses, Mycobacterial Antigens, Tissue-invasive Helminth Parasites, Cytokines
- Medical subject headings
- Mycobacterium Infections, Tuberculosis, Filariasis, Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Latent TB positive with helminth positive | |
| 2 | Latent TB positive with helminth negative |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the immune responses to mycobacterial antigens, including PPD and Mycobacterium tuberculosis culture filtrate protein, in individuals who are LTBI+ Hel- versus those who are LTBI+Hel+
pending
Measured: 5 years
Secondary outcomes (1)
To compare immune responses to mycobacterial antigens in LTBI+ Hel+ co- infected individuals, before and after treatment for filarialinfection.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2012 (estimated)
- Study start1 Jan 2013
- Primary completion14 Nov 2019
- Study completion7 Aug 2020
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 Mycobacterium InfectionsStudies 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 4,268 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Thomas B Nutman, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01547884
- Sponsor's protocol ID
- 999912073
- Other IDs
- 12-I-N073
- Status last verified
- Apr 2021
- First submitted
- 6 Mar 2012
- Last updated
- 20 Apr 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Metenou S, Babu S, Nutman TB. Impact of filarial infections on coincident intracellular pathogens: Mycobacterium tuberculosis and Plasmodium falciparum. Curr Opin HIV AIDS. 2012 May;7(3):231-8. doi: 10.1097/COH.0b013e3283522c3d.
PubMed 22418448Babu S, Nutman TB. Helminth-Tuberculosis Co-infection: An Immunologic Perspective. Trends Immunol. 2016 Sep;37(9):597-607. doi: 10.1016/j.it.2016.07.005. Epub 2016 Aug 5.
PubMed 27501916Salgame P, Yap GS, Gause WC. Effect of helminth-induced immunity on infections with microbial pathogens. Nat Immunol. 2013 Nov;14(11):1118-1126. doi: 10.1038/ni.2736.
PubMed 24145791
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Filarial Infection on Antigen-Specific Immune Responses in Latent Tuberculosis
- ClinicalTrials.gov ID
- NCT01547884
- Acronym / sponsor ID
- 999912073
- Keywords
- T Cells, Immune Responses, Mycobacterial Antigens, Tissue-invasive Helminth Parasites, Cytokines
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 4,268 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 1 Jan 2013 (actual)
- Primary completion
- 14 Nov 2019 (actual)
- Study completion
- 7 Aug 2020 (actual)
- First posted
- 8 Mar 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:
- Lymphatic filariasis is an infection that is caused by small, thread-like worms. It is spread by mosquitoes, and causes fever, chills, and headaches. If untreated, it can also cause elephantiasis, a condition that leads to swelling of the arms, legs, breasts, and scrotum. Treatment can eliminate the worms from the blood and reduce the risk of developing elephantiasis. Researchers want to study people with latent tuberculosis (TB) who may or may not be infected with filariasis. This study will look at the way that people with latent TB fight infection with these worms.
Objectives:
- To study how the immune systems of people with latent TB react to filarial infection.
Eligibility:
- Individuals between 18 and 65 years of age who have latent TB and may or may not have filarial infection.
Design:
- Participants will be screened with a physical exam and medical history. They will provide a blood and stool sample to test for infection.
- Participants who do not have lymphatic filariasis but have another kind of intestinal worm will be treated for the parasite. This will be their last study visit.
- Participants who have latent TB and lymphatic filariasis will be treated with the standard treatment for the disease. They will come back for a second visit 6 months later, and will provide another blood sample.
Detailed description
Tissue-invasive helminth parasites infect close to 500 million people worldwide and are associated with strong T helper (Th)2 responses and regulatory networks that downregulate potentially protective Th1 responses. The two common tissue invasive helminth parasites are Wuchereria bancrofti, that causes lymphatic filariasis and Strongyloides stercoralis, that causes stronyloidiasis. Previous studies have shown that the intestinal helminth coinfection is accompanied by lowered in vitro production of interferon-gamma and elevated production of interleukin 10 in individuals with active pulmonary tuberculosis (TB). Our team has recently shown that co-existent filarial TB infections down-regulate Th1 and Th17 responses, which are necessary for protection against active TB.
The current study will compare immune responses to mycobacterial antigens in individuals with latent tuberculosis (LTBI+) and concomitant helminth infection (Hel+), including those with filarial (Fil+) and strongyloides (STR+) infection versus those with LTBI+ without concomitant helminth infection (Hel-). Immune responses to mycobacterial antigens from co-infected individuals will also be evaluated before and after treatment for helminth infection. Individuals (n=4000) will sign a screening consent prior to undergoing any study procedures. Every participant will have their medical history collected and will undergo a physical exam and a tuberculin 2TU purified protein derivative (PPD) skin test; women of childbearing potential will also undergo a urine pregnancy test, and those with positive test results will be excluded from the study. Individuals with positive PPD skin test results (> or = 5 mm) and no symptoms of active TB will have their blood drawn (5 mL) as part of the screening procedures to confirm LTBI+ status, evaluate circulating filarial antigenemia, determine Strongyloides status by ELISA, measure hematocrit levels, and for storage of serum samples; those with PPD skin test results less than or equal to 5 mm will be excluded from the study. Individuals with positive symptoms for TB will also be excluded from the study, but sputum will be collected from them, and those with positive smears will be referred for treatment. Individuals will be matched for age, gender, and geographic location, and they will be assigned to one of two groups, LTBI+ Hel+ (n=100) or LTBI+ Hel- (n=100).
Within 3 months of screening, individuals will be asked to sign an on-study consent and will undergo a second blood draw (10 mL) for immunological investigations and storage of serum samples; women of childbearing potential will undergo a repeat urine pregnancy test, and those with positive test results will be excluded from further study. Stool samples will also be collected for microscopic evaluation of ova and parasites. LTBI+ Fil+ individuals will be treated with a single standard dose of albendazole (400 mg) and single standard dose of diethylcarbamazine citrate (300 mg), which are available through the National Programme for the Elimination of Lymphatic Filariasis in India. LTBI+ STR+ individuals will be treated with a single standard dose of ivermectin (12mg) and a single standard dose of albendazole (400mg). These individuals will be asked to return 6 months after treatment to undergo a third blood draw (10 mL) for additional immunological investigations and storage of serum samples. LTBI+ Hel-individuals who test positive for other intestinal helminth infection will be treated with a single standard dose of albendazole (400 mg).
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Latent TB positive with helminth positive |
| 2 | – | –Latent TB positive with helminth negative |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The screening will be a community-based study in South India. Study participants will be recruited from villages in the Kancheepuram District, where approximately 6% of the population tests positive for circulating filarial antigens [31]. PPD skin test reactivity in this population is virtually 100% to PPD-B (battery) and 60% to 70% to PPD-S (standard) by age 24, and the incidence of active TB is about 4 per 1000 individuals [31]. While the rate of positivity of the tuberculin skin test to the 2TU PPD test is not known, significant deviation in the percent positivity from skin tests using 1TU is not expected based on findings reported elsewhere [32]. However, we are revising the @@@screening sample number on the basis of preliminary data from the current study that shows that the prevalence of latent TB in this population is around 25% and filariasis is around 1%. In addition, preliminary data from these areas show that the prevalence of Stronglyloides infection is around 10%.
Key inclusion criteria (0 listed)
Key exclusion criteria (2 listed)
- Pregnancy: Pregnant and lactating women will be excluded from the study because the safety of DEC or ivermectin has not been adequately evaluated during pregnancy or lactation, while albendazole is a Category C drug found to be teratogenic in animals, and it poses a potential risk during breastfeeding.
- EXCLUSION OF CHILDREN: Children (<18 years of age) will not be included in this study due to the fact the prevalence of filarial and strongyloides infection in children has been found to be very low in South India.
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
To compare the immune responses to mycobacterial antigens, including PPD and Mycobacterium tuberculosis culture filtrate protein, in individuals who are LTBI+ Hel- versus those who are LTBI+Hel+
Time frame: 5 years
pending
1 secondary outcome
To compare immune responses to mycobacterial antigens in LTBI+ Hel+ co- infected individuals, before and after treatment for filarialinfection.
Time frame: 5 years
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 20 Apr 2021.
- Background: PubMed 22418448Metenou S, Babu S, Nutman TB. Impact of filarial infections on coincident intracellular pathogens: Mycobacterium tuberculosis and Plasmodium falciparum. Curr Opin HIV AIDS. 2012 May;7(3):231-8. doi: 10.1097/COH.0b013e3283522c3d.
- Background: PubMed 27501916Babu S, Nutman TB. Helminth-Tuberculosis Co-infection: An Immunologic Perspective. Trends Immunol. 2016 Sep;37(9):597-607. doi: 10.1016/j.it.2016.07.005. Epub 2016 Aug 5.
- Background: PubMed 24145791Salgame P, Yap GS, Gause WC. Effect of helminth-induced immunity on infections with microbial pathogens. Nat Immunol. 2013 Nov;14(11):1118-1126. doi: 10.1038/ni.2736.
Related trials for Mycobacterium Infections
RecruitingPhase 4
Short-term Antibiotic Therapy in Mycobacterium Avium Complex Pulmonary Disease
Mycobacterium Avium Complex Pulmonary Disease
RecruitingObservational study
Study of Mycobacterial Infections
Mycobacterium Infections
Not yet recruitingPhase 2
Telacebec in Adults With Multibacillary Leprosy (TEBULA Leprosy Trial)
Leprosy, Multibacillary
RecruitingPhase 4
Prevention of Recurrence With Cordyceps Sinensis in Mycobacterium Avium Complex Pulmonary Disease
Mycobacterium Avium Complex Pulmonary Disease
RecruitingPhase 4
Short-term Bactericidal Effect of Contezolid in MAC-PD
Mycobacterium Avium Complex Pulmonary Disease
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.
Thomas B Nutman, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mycobacterium Infections and Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in 2 countries.
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 0 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 20 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, India. 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?
To compare the immune responses to mycobacterial antigens, including PPD and Mycobacterium tuberculosis culture filtrate protein, in individuals who are LTBI+ Hel- versus those who are LTBI+Hel+ (time frame: 5 years). 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 NCT01547884, 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 20 Apr 2021.