23 Clinical Trials for Various Conditions
Background: Tuberculosis (TB) is a severe disease and a major cause of death in many people worldwide. It is caused by a bacteria that enters through the lungs and can spread elsewhere in the body. People with latent TB have the bacteria that lie dormant but can become active and cause disease. These people are offered treatment to prevent development of active TB. Worldwide, a lot of people with LTBI also have a parasitic worm called a helminth that can stay in the gut or the blood. These parasites can affect the immune system and cause diseases like TB to become worse. Researchers want to see how helminth infection makes it harder for people to fight TB infection. Objectives: - To study how the immune system of people with latent tuberculosis infection (LTBI) acts to prevent development of active TB. Also, to study how helminth infection might affect this immune response. Eligibility: * Adults age 18 70 with LTBI as defined by an approved blood test called QuantiFERON TB Gold. * No evidence of infections like Hepatitis or HIV * Pregnant subjects and subjects taking medications that suppress the immune system are not eligible. * Have not received prior treatment for LTBI. Participants might be still eligible if prior treatment for active TB has been received Design: Screening phase: - Participants will be screened with medical history, physical exam, and blood tests for other infections/conditions which might affect the immune system. They will have testing for active TB i.e. blood testing as well as testing of their spit, scans and X-rays. Baseline phase: * Only eligible participants will be entered into the study. * Participants will have interviews, medical history, and physical exam. * Blood will be drawn from an arm vein for testing. * Participants will collect stool samples at home for 3 days in a row to test for helminth infection.. * Participants may have apheresis. Blood cells are removed by needle. They pass through a separator machine which returns everything but the cells back to the participant. * Participants may have procedures at the start and end of the study that let researchers look into the lungs and collect cells. Study phase, about 2 years: * All participants will be offered treatment for LTBI which lasts 6-9 months. * Participants being treated for LTBI will have about 11 study visits. They will visit monthly for 9 months while on treatment, then 6 and 12 months after treatment. * Participants not eligible/refusing treatment for LTBI will be made aware of active TB, then have 3 other visits, about 6, 12, and 24 months after the baseline visit. * Participants who have helminth infection will receive appropriate treatment. * All participants will have blood drawn at each visit.
This is a prospective cohort study of persons tested for latent tuberculosis infection at either high risk for exposure to Mycobacterium tuberculosis or high risk for progression to tuberculosis disease. The study will assess the relative performance and cost of three diagnostic tests for latent tuberculosis infection (tuberculin skin test, QuantiFERON-TB Gold In-Tube, and T-SPOT.TB) and will examine the rates of positive results among the cohort. This study will also determine the risk and rate of progression to active TB disease, overall and by the results of the three tests.
This study will examine how the immune system responds to infection with Mycobacterium tuberculosis bacteria (bacteria that cause tuberculosis) in order to better understand how the germ produces infection and how the immune response might work to control the infection. Only about one in 10 people infected by M. tuberculosis become sick, sometimes years or even decades after exposure. It is not known why some people become sick and most do not, but the immune system of people who never develop disease may be better able to control the bacteria. This study will evaluate the latent form of M. tuberculosis infection to further the understanding of the immune mechanisms - particularly the role of certain white blood cells - involved in the disease process. Healthy volunteers 18 years of age and older may be eligible for this study. Candidates are screened with a medical history, family history of medical conditions, sexual history, history of drug use, physical examination and blood tests, including a test for HIV. People in Mali, West Africa, and in local health clinics in the United States may participate. At the start of the study, participants have blood tests and a tuberculin skin test (PPD test), which indicates whether a person has been exposed to tuberculosis bacteria. For the PPD, a tiny amount of liquid containing dead tuberculosis antigen is put under the skin of the forearm with a needle. The antigen cannot cause infection or disease. After 3 days, participants have another blood test and the site of the tuberculin test is examined for swelling that would indicate a positive result. Participants with a positive PPD have a chest x-ray to check for tuberculosis disease. Those whose x-ray is also positive are withdrawn from the study and referred to their doctor for evaluation and treatment. Those whose x-ray is negative return to the clinic within 3 weeks of the tuberculin test to give another blood sample. Participants whose PPD is negative have a second tuberculin test 10 to 21 days later and return 3 days after the test to determine if it is still negative or if it is positive. (Some people who are negative after the first test may test positive after the second procedure.) Those whose test is still negative end their participation in the study at that time. Participants whose second PPD is positive have a chest x-ray as described above, and those with a negative chest x-ray return in 3 weeks to donate one last blood sample. The purpose of the present study is to evaluate the latent form of this infection, the prevalence of which worldwide exceeds that of active disease. Our hypothesis is that in latent tuberculosis antigen specific effector memory CD4+ T cells are responsible for the generation of clinically measurable delayed type hypersensitivity and that central memory CD4+T cells are not directly involved in this process. We base this idea on the assumption that latent tuberculosis is a state of antigen persistence and that effector memory T cells should be maintained as long as antigen/infection is present. We propose to conduct this study in Mali, West Africa and local clinics in the U.S. Tuberculosis affects 593/100,000(2) individuals in Mali and most have been exposed to the disease. Additionally it would be important to evaluate the same parameters locally as latent infection is one of the major factors for reactivation tuberculosis in this country. Patients would be enrolled in 4 major groups: HIV-/TST- (Group A), HIV-/TST+ (Group B), HIV+/TST+(G roup C) and HIV+/TST- (Group D). To evaluate this hypothesis we plan to enroll between 100 - 300 patients over the course of 2 years from both countries. Blood samples before and at predetermined time points after the application of Purified Protein Derivative (PPD) will be obtained to determine the fraction of CD4+ T cells which produce interferon gamma in response to stimulation with PPD with a 16hr antigen stimulation assay. Appropriate staining will be done to ascertain the phenotype as well as cytokine production (Interferon gamma,( IFN gamma), Interleukin 2 (IL2) and Tumour Necrosis Factor ( TNF)). Additionally lymphocyte proliferation will be studied using 5-(and-6)-carboxyflouorescein diacetate succinimidyl ester (CFSE.) In conducting this study we hope to further the understanding of the immune mechanisms involved, particularly mechanisms of T cell memory, which would provide insights into TB and HIV pathogenesis. We also believe that understanding these mechanisms could lead towards establishment of surrogates for immunity in TB vaccine studies, which could enhance vaccine trial design. It might also help in understanding better the immunological dynamics of tuberculosis co-infection in individuals with HIV infection.
The purpose of this study is to determine the pharmacokinetics (how a drug is absorbed, distributed, and eliminated by the body) of moxifloxacin alone versus moxifloxacin given with rifapentine. Researchers believe that understanding how these tuberculosis drugs interact when given together may help to determine the best drug treatment plan for use in future studies. Volunteers will take moxifloxacin daily by mouth for the first part of the study and then moxifloxacin in combination with rifapentine during the second part of the study. Sixteen healthy men and women will be recruited from Johns Hopkins University School of Medicine to volunteer for this study. They will be required to stay in the inpatient unit twice, each time for 84 hours. Study procedures will include having a tube placed in a vein to draw several blood samples over time. Volunteers will participate in the study for a maximum of 48 days, including screening and follow-up visits.
This study will test a method of detecting tuberculosis-causing bacteria that are resistant to current medication treatments. Blood samples will be collected from patients from 3 sites and 3 mainly Hispanic populations in Texas, Mexico, and Colombia. Up to 780 males and females, ages 18-85 years, will participate. The study population will consist of 390 people with any of 3 forms of tuberculosis (TB) and 390 people who are either healthy or with a disease initially thought to be one of these 3 forms of TB but then ruled out. Volunteers will only be contacted, invited to participate and interviewed at the beginning of their evaluation for possible TB.The study team will follow up with the health department to determine if the volunteer was indeed diagnosed with TB, and with the laboratory to determine the results of TB tests at diagnosis and during the course of treatment.
A Phase 1, Drug-Drug Interaction Study to Evaluate the Safety, Tolerability, and the Induction Potential of TBAJ-876 on CYP3A4 and P-glycoprotein and the Inhibition Potential of TBAJ-876 on P-glycoprotein in Healthy Adult Subjects
A Phase 1, Partially Blind, Placebo Controlled, Randomized, Combined Single Ascending Dose (SAD) with a Food Effect Cohort (Part 1), Multiple Ascending Dose (MAD) (Part 2), and Relative Bioavailability (rBA) (Part 3) Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TBAJ-876 in Healthy Adult Subjects
Tuberculosis has been shown to make immune genes inaccessible and slows immune response The purpose of this research is to see if if azacitidine is safe and can return the ability of the body to resist tuberculosis (TB), a contagious infection that attacks the lungs. Individuals with tuberculosis are being asked to participate. Some will receive a drug to restore a host immunity while others can choose to receive standard of care. All patients will continue to receive standard of care tuberculosis therapy regardless of whether they chose to participate in the study. This study is a Phase Ib/IIa single-institution, open-label, non-randomized clinical trial of sub-cutaneous azacitidine in pulmonary TB patients during the continuation phase of ATT.
This is a Phase I open-label, dose escalation trial to evaluate the use of Tice® BCG as a challenge for future assessment of in vivo TB immunity. Subjects will be recruited from the target population reflecting the community at 2 VTEU sites. Enrollment will occur over 14 months. Subjects who provide informed consent will be screened, and up to 120 eligible, HIV and TB uninfected subjects, 18-45 years, inclusive, will be enrolled for study interventions and sequentially assigned to 1 of 4 dose groups. Doses of Tice BCG from 2 to 16x10\^6 cfu will be delivered ID in a dose escalation format to 4 groups of 30 subjects per dose group. Primary Objectives: 1) Evaluate the safety of different doses of ID Tice BCG for use as a human challenge model for TB infection. 2) Examine shedding from ID challenge sites after administration of different doses of Tice BCG in TB naive healthy subjects. 3) Evaluate the reproducibility of BCG shedding over time with both quantitative PCR and culture.
The Pulmonary Colonization Test is a non-invasive breath test for markers of lower respiratory tract infection, which may predict the probability of mycobacterial organisms in the lower respiratory tract. It consists of: * A breath collection apparatus for collection of volatile organic compounds in breath onto a sorbent trap and Tedlar bag, as well as for the collection of a separate sample of room air. * Analysis of the volatile organic compounds in breath and room air by short acoustic wave/gas chromatography. * Interpretation of the volatile organic compounds with a proprietary algorithm in order to predict the probability of lower respiratory tract colonization and infection. * Analysis of the volatile organic compounds in sputum culture by short acoustic wave/gas chromatography. This study will test the hypothesis that the investigators can identify the presence of mycobacteria in an individual by sampling the breath of patients with active tuberculosis and by sampling "head space" above culture media of sputum provided. This study will test the hypotheses: * that the investigators can identify positive cultures for mycobacterium tuberculosis through sampling of the headspace above the cultures prior to standard laboratory culture identification * that the investigators can identify control of tuberculosis by sampling exhaled breath
Background: - Tuberculosis (TB) is an infectious disease that affects numerous people worldwide. Researchers are interested in actively recruiting individuals with TB for research and treatment studies. Objectives: - To collect blood and other samples to study the natural history of tuberculosis. Eligibility: - Individuals 2 years of age and older who have either active or latent tuberculosis. Design: * Latent TB patients: Participants will have a single study visit with a physical examination and medical history, and will provide blood samples for testing. * Active TB patients: Participants will have an initial visit with a physical examination and medical history, and will provide blood samples for testing. Participants will also provide sputum samples if required, and may have an optional skin punch biopsy to collect a sample of skin tissue for study. * Treatment for active TB will be provided as part of this protocol. * Active TB participants may be asked to return for study visits every 1-2 months while receiving treatment....
The purposes of this study are to determine: how safe it is to take SQ109 (an experimental tuberculosis treatment) once a day by mouth for up to 2 weeks in 2 different dosages; how well the body accepts it; how SQ109 enters and leaves the body and blood tissues over time; the amounts that can be detected in the blood; and how long it stays in the body. The study involves 30 volunteers: 24 will receive SQ109 and 6 will receive placebo (inactive substance). Qualified participants will be admitted to the study unit within 28 days from the screening and stay as inpatient for approximately 2 weeks. During this period they will receive study drug and complete all scheduled procedures including multiple blood draws. After discharge, there is a 14 day follow up period. Total study participation is about 56 days.
Primary Objective: 1. To evaluate the performance of the new T-SPOT.TB test and the conventional TST for screening of Latent Tuberculosis infections in patients with cancer and those undergoing Hematopoietic Stem Cell Transplant. Secondary Objectives: 1. To examine the factors associated with positive response to T-SPOT.TB and the TST (tuberculin skin test) in patients with anergy. 2. To determine the impact of immunosuppressive and antineoplastic therapy on the screening performance of T-SPOT.TB and the TST in cancer patients.
To demonstrate, in patients with tubercular or nontubercular mycobacterium infections with or without HIV infection, the safety of thalidomide use as judged by symptoms, physical exam, and studies of microbiologic, immunologic, hematologic, renal, and hepatic status. To demonstrate efficacy of the drug as judged by status of fever, nutrition, tuberculosis lesions, and immune responses.
PRIMARY: To estimate the proportion of tuberculosis patients in the CPCRA who have drug-resistant tuberculosis (TB) and to describe the patterns of drug resistance. SECONDARY: To compare drug resistance data on the Mycobacterium tuberculosis isolates of HIV-infected patients to those of HIV-uninfected patients who are being followed in the CPCRA. To assess the relationship of resistance data with geographic, demographic, and HIV and TB risk factor information. Geographic areas and demographic subgroups affected by the TB epidemic appear to be congruent and associated with the concurrent HIV epidemic. The total number of CPCRA patients who will develop, or who have experienced, confirmed TB is unknown. It is critical to determine the depth and breadth of the current problem of drug-resistant TB.
To evaluate and compare the safety and effectiveness of a one-year course of isoniazid (INH) versus a two-month course of rifampin plus pyrazinamide for the prevention of reactivation tuberculosis in individuals infected with both HIV and latent (inactive) Mycobacterium tuberculosis. Current guidelines from the American Thoracic Society and the Centers for Disease Control recommend 6 to 12 months of INH for PPD (purified protein derivative)-positive individuals. Although the effectiveness of this treatment is not known for HIV-infected individuals, several studies using INH to prevent tuberculosis in presumably normal hosts have shown 60 to 80 percent effectiveness. Problems with this treatment include compliance, adverse reaction, and the possibility of not preventing disease due to tuberculosis organisms being resistant to INH. A two-month preventive treatment plan should help in increasing compliance. In addition, the use of two drugs (rifampin / pyrazinamide) may help overcome problems with drug resistance. If this study shows equal or greater effectiveness of the two-month rifampin / pyrazinamide treatment, it could alter the approach to tuberculosis prevention for both HIV-positive and HIV-negative individuals.
About 10 people with cystic fibrosis (CF) and persistent Nontuberculosis mycobacteria (NTM) infection despite treatment will be screened to find out if their NTM infection has at least one mycobacteriophage that is effective in killing the mycobacteria. Individuals who are found to have at least one phage will be offered assistance in pursuing FDA approval for treatment via expanded-access Individual New Drug (IND) for compassionate-use. They will receive phage treatment for 1 year along with their guideline-based antibiotics for NTM. Individuals who are not identified as having a phage match will be followed as they continue to receive guideline based antibiotic therapy for 1 year. All subjects, including those who do not have a phage match will continue to be observed for the duration of the study, or about 1 year.
Background: Many people around the world get tuberculosis (TB) and non-tuberculous mycobacteria (NTM) infections. Sometimes medicine that treats these infections does not get to where the bacteria are in the lungs. Researchers want to find a way to tell if enough medicine is getting to where it is needed in the lungs. They will look at how much medicine is in your sputum (what you cough up) compared to how much is in your blood. They will also investigate a new test to quickly figure out what medicines are likely to treat TB effectively. Objective: To determine the relationship between the concentration of TB drugs in plasma and sputum over time. Eligibility: People ages 18 and older who have TB or NTM infection that is suspected to be drug resistant. They must be taking TB or NTM medicines. Design: Participants will be screened with medical history. Participants will be in the study for 2 8 days. Participants will give 3 or more sputum samples over at least 2 different days. They will cough sputum into a cup. Participants will have blood drawn 4 times a day on 2 different days.
To evaluate the efficacy and safety of azithromycin given chronically for the treatment of serious nontuberculous mycobacterial infection in patients failing or intolerant of other available therapy.
This is pilot study of the immunologic effects of intradermal Bacille Calmette-Guerin (BCG) vaccination of adults with cystic fibrosis (CF), non-CF bronchiectasis (NCFB), and healthy volunteers.
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.
This study will determine what dose of recombinant interferon-gamma is safe and effective for treating multiple drug-resistant tuberculosis. Recombinant interferon-gamma is a genetically engineered form of a substance normally produced by the body and is used to boost immune function. Patients 5 years of age and older with multiply drug-resistant tuberculosis may be eligible for this study. Participants will be admitted to either the NIH Clinical Center in Bethesda, Maryland, the Texas Center for Infectious Diseases in San Antonio or the South Texas Hospital or Valley Baptist Hospital, both in Harlingen, Texas. On admission, patients will have a medical history, physical examination, blood and urine tests, sputum culture, X-rays, pulmonary function tests and a computed tomography (CT) scan. CT produces 3-dimensional images of body tissues and organs in small sections. For the procedure, the patient lies still on a table surrounded by the scanner. All patients will continue treatment with anti-tuberculosis antibiotics during and after the study period and may elect whether or not to take gamma interferon in addition to the antibiotic. Five patients will receive only antibiotic treatment, and 5 each will receive one of 3 doses (0.025, 0.05 or 0.1 milligrams per square meter of body surface area) of interferon-gamma injected under the skin 3 times a week. The patient or caregiver will be taught to give the injections, which are similar to insulin injections for diabetes. Patients will be in isolation in the hospital from the start of therapy until sputum samples show no evidence of tuberculosis for 3 consecutive weeks. Following that, they will repeat the tests done on admission (except CT) during follow-up visits (1- to 2-day hospitalizations) at 3, 6, 9, 12, 15, 18 and 24 months after the start of therapy. Patients taking interferon gamma will have blood drawn more frequently (monthly) for the first 6 months, and patients with lung infection will have sputum samples collected more frequently-weekly for the first 3 months or until three consecutive negative samples are obtained and then monthly throughout the course of therapy. Patients with lung infection will also have repeat CT scans at 6 and 12 months while on interferon gamma. In one or two patients on the drug, blood will be drawn frequently following one injection of gamma interferon (just before the injection and again at 0.25, 0.5, 1, 6, 12, 18, 24 and 48 hours after it) to see if a difference in blood levels of the drug can be detected.
Background: -Tuberculosis (TB) is an infection of the lungs caused by bacteria. In Mali, TB is diagnosed with a test that is fast and inexpensive but not always accurate. The purpose of this study is to test a new method for diagnosing TB, called the microscopic-observation drug-susceptibility (MODS) test. The MODS test takes 7 days to show results. The test also gives information on which drugs will work best in each case. Objective: -To test a new method for diagnosing tuberculosis called the microscopic observation drug susceptibility test. Eligibility: * Participants must be 12 years of age or older. * They must have a diagnosis of TB from a sputum smear, or have symptoms of TB and an x-ray indicating that TB is present. Design: * Participants will take part in the study from 6 months to 21 months and be assigned to one of three groups, depending on what type of TB they have. * At the first visit, researchers ask questions about general health and symptoms of TB. They check vital signs, draw blood, and ask for a sputum sample. The blood is used to check for HIV infection and for the number of CD4 cells, which measures the severity of the HIV infection. * The 2-, 5-, and 6-month visits are similar to the first. Those who do not have multidrug-resistant (MDR) TB will end their participation after the 6-month visit. MDR TB is tuberculosis that has not responded to isoniazid and rifampicin. Participants with MDR TB will remain in the study for 21 months. * No treatment is provided as part of this study.