Effect of Filarial Infection on Immune Responses in Latent Tuberculosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01547884
First received: March 6, 2012
Last updated: May 31, 2014
Last verified: November 2013
  Purpose

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.

Condition
Tuberculosis
Filariasis

Study Type: Observational
Study Design: Time Perspective: Prospective

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To compare the immune responses to mycobacterial antigens, including PPD and Mycobacterium tuberculosis culture filtrate protein, in individuals who are LTBI+ Fil- versus those who are LTBI+ Fil+.

Secondary Outcome Measures:
  • To compare immune responses to mycobacterial antigens in LTBI+Fil+ co-infected individuals, before and after treatment for filarialinfection.

Estimated Enrollment: 4000
Study Start Date: February 2012
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. Previous studies have shown that the intestinal helminth coinfection is accompanied by lowered in vitro production of interferon g 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 filarial infection (Fil+) versus those with LTBI+ without concomitant filarial infection (Fil-). Immune responses to mycobacterial antigens from co-infected individuals will also be evaluated before and after treatment for filarial infection. Subjects (n=4000) will sign a screening consent prior to undergoing any study procedures. Every subject 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 equal to 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, measure hematocrit levels, and for storage of serum samples; those with PPD skin test results less than or equal to 12 mm will be excluded from the study. Subjects 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+ Fil+ (n=60) or LTBI+ Fil- (n=60).

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. 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+ Fil- individuals who test positive for intestinal helminth infection will be treated with a single standard dose of albendazole (400 mg).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • SUBJECT INCLUSION CRITERIA:

Subjects (18 to 65 years of age) who meet the following criteria are eligible to participate in the study:

  • Positive tuberculin PPD skin test result (> or equal to 5 mm) and IGRA+.
  • Willingness to provide blood and stool samples for examination.
  • Willingness to have samples stored for study participants only.

SUBJECT EXCLUSION CRITERIA:

Subjects are not eligible to participate if they meet the following criteria:

  • Pulmonary symptoms suggestive of TB (cough > 3 weeks in duration and/or intermittent fever > 1 week in duration and/or hemoptysis).
  • Tuberculin skin test within the last 6 months prior to screening.
  • Women who are pregnant or breastfeeding.
  • Known documented cases of cancer, acquired immune deficiency syndrome, or other immunosuppressive illness.
  • History of any other illness or condition which, in the investigator s judgment, may substantially increase the risk associated with the subject s participation in the protocol, or it may compromise the scientific objectives.
  • Consumption of DEC in the last one year prior to screening.
  • EXCLUSION OF WOMEN:
  • Pregnancy: Pregnant and lactating women will be excluded from the study because the safety of DEC 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 due to the fact the prevalence of filarial infection in children has been found be very low in South India.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01547884

Contacts
Contact: Thomas B Nutman, M.D. (301) 496-5398 tnutman@mail.nih.gov

Locations
United States, Maryland
National Institute of Allergy and Infectious Diseases (NIAID), 9000 Rockville Pi Recruiting
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Thomas B Nutman, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT01547884     History of Changes
Other Study ID Numbers: 999912073, 12-I-N073
Study First Received: March 6, 2012
Last Updated: May 31, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Immune Responses
Mycobacterial Antigens
Tissue-invasive Helminth Parasites

Additional relevant MeSH terms:
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections
Nematode Infections
Parasitic Diseases
Secernentea Infections
Spirurida Infections
Filariasis
Tuberculosis
Helminthiasis

ClinicalTrials.gov processed this record on October 23, 2014