Clinical Research Directory

Effects of Food Intake on Biomarker Activity in Normal Humans Taking Immulina

The need for a generally available product that can safely and effectively increase antiviral resilience in susceptible populations became highly relevant during the recent COVID pandemic. The value continues with the endemic influenza season, which is now joined by COVID and, in susceptible adults, respiratory syncytial virus. The investigators recently completed a NIH-funded U19 project examining the immune potentiating effects of Immulina supplementation on biomarkers associated with antiviral resilience. Results showed robust NK responses in a substantial minority of participants. Further work has shown that the active compounds in Immulina (Braun-type lipoproteins) may be susceptible to degradation under GI conditions that are typically found during digestion after a meal (such as locally elevated intestinal pancreatic lipase and surfactant levels in the post meal state). In the investigators initial study, no instruction was given about when to take the investigational product in relationship to a meal or any restrictions on fat content indicating a possible spectrum of intestinal chemical conditions that could have affected the bioactivity of Immulina in different members of the study cohort. Because of the heterogeneous immune biomarker response in the investigators U19 study cohort, the investigators propose to explore the role of food presence when ingesting the supplement and its possible impact on the immunostimulatory properties of Immulina. The investigators will address this question by seeking to characterize and optimize the oral delivery of Immulina through evaluating product quality, bio accessibility, and stability under simulated GI conditions relevant to fasting and fed states. This will be accomplished through botanical authentication, bioassay-based standardization, and dissolution performance of the clinical encapsulated product to ensure consistency with previously characterized material. Additionally, investigators will perform in vitro studies to identify dietary conditions most likely to preserve Immulina activity. Further, an additional pharmacodynamic study will be performed with various Immulina doses over four weeks in individuals who will fast for 2 hours or have just completed a meal after taking daily dose of Immulina to compare the effects of fed vs 2 hr. fasting after ingesting Immulina on biomarkers of antiviral resilience. Finally, investigators will examine the effects of a 4-week pretreatment with Immulina vs. placebo on vaccine-specific antibody titers after routine influenza immunization by comparing vaccine-specific antibody titers immediately prior and 4 weeks after immunization. These studies will allow optimal design of future clinical trial protocols to assess impact of daily Immulina on antiviral resilience in susceptible populations with or without known immune compromise due to concomitant disease (e.g. cancer, transplant, etc.) or age (e.g., immune senescence).

Rechallenge With a Low Pathogenicity Avian H10N7 Influenza Virus in Healthy Human Volunteers Previously Challenged With H10N7 Influenza

Background: Influenza (flu) is a virus that can infect humans and animals. In humans, the flu can cause mild symptoms such as fever, cough, sore throat, runny nose, muscle aches, headaches, and fatigue. It can also cause sinus infections or pneumonia. Some flu strains, such as H5N1 and H7N9, which come from birds, can lead to more severe symptoms or death. Others, like H10N7, also come from birds but usually cause mild symptoms. Researchers want to study bird flu in humans to help develop new flu vaccines and treatments. Objective: To learn more about how bird flu viruses infect humans. Eligibility: Healthy people aged 18 to 55 years who were infected with the H10N7 bird flu strain as part of a previous study. Design: Participants who were infected with H10N7 in a previous study will be infected again with the same virus. The virus will be sprayed into their nostrils. Participants will stay in the hospital for at least 9 days. They will stay in an isolation unit. No outside visitors will be allowed. During their stay, participants will provide blood, urine, and nasal fluid samples. They will have tests of their heart and lung function. They will complete questionnaires about their symptoms. Participants will remain in the hospital until they test negative for the flu 2 days in a row. They will continue to complete questionnaires about their symptoms for 2 weeks after they were infected with the virus. Participants will have 2 follow-up visits, at 5 weeks and 9 weeks after they were infected. They will have a physical exam and provide samples of blood and nasal fluids. They will have a test of their heart function. ...

Host Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA. a Prospective Study Will Evaluate the Performance of Direct LS-TA in Triage Febrile Patients Into Major Categories of Infections: Viral, Bacterial or Active Tuberculosis.

Febrile illness is a common condition and it is crucial to have an early triage of patients according to various aetiologies to enable appropriate treatment. Currently, most screening/diagnostic tests target the detection of pathogens, while only a few assays aim to understand the host response, and they are mostly based on a measurement of serum proteins (e.g. CRP or procalcitonin). Recently, blood transcriptome has been explored to differentiate bacterial and viral infections. However, gene expression in blood represents a composite score of gene expression of all the component cell-types present in the sample. Here, we propose to develop a rapid test that can determine gene expressions of a specified single cell type in peripheral blood (e.g., monocytes or granulocytes) as a host response biomarker to differentiate three major categories of infections that are bacterial, viral, and tuberculosis The assay is called Direct Leukocyte Single cell-type transcript abundance (TA) assay (DIRECT LS-TA) as it can directly determine the gene expression of a specified single cell-type among various other leukocyte populations directly in a peripheral blood sample. Such results signify the nature of host response according to 3 or more axes (Type I or Type II interferon signaling response or pro-inflammatory cytokine signaling) And it can be used to indicate the type of underlying infection (viral, bacterial, or active tuberculosis).

Host Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA

Febrile illness is a common condition, particularly among young patients and it is crucial to have an early triage of patients according to various aetiologies to enable appropriate treatment. Most diagnostic tests are targeted towards the detection of pathogens while other assays are mostly related to serum proteins. Blood cells transcriptome has been explored to differentiate bacterial and viral infections. Here, we propose to develop a rapid test using the host responses in terms of gene expressions of single-cell populations of peripheral leukocytes (monocytes and granulocytes) to differentiate three major categories of infections that are bacterial, viral, and tuberculosis. The assay is called Direct leukocyte single cell-type transcript abundance (TA) assay (DIRECT LS-TA) as it can directly determine the gene expression of a specified single cell-type (e.g. monocytes and granulocytes) among various leukocyte cell populations directly in a peripheral blood sample. Such results signify the nature of host response and can be used to indicate the type of infection (viral, bacterial or active tuberculosis).