Clinical Research Directory

Longitudinal Deep Phenotyping of Central Mechanisms in Dysosmia: A Pilot Study Using Electrobulbogram (EBG), Functional MRI (fMRI), and Diffusion-Weighted Imaging (DWI)

Background: Loss of the sense of smell can seriously affect a person's quality of life. The ability to smell can be damaged by many factors, including illnesses, injuries, and exposure to toxic chemicals. The effects can vary, including complete loss of smell, partial loss, and parosomia, which is when things smell differently than they should. Objective: To study how brain function changes in people with different types of smell disorders. Also, to look at how smell loss affects quality of life over time. Eligibility: People aged 18 years or older with a disorder that affects their sense of smell. Healthy volunteers are also needed. Design: Participants will have 5 study visits over 1 year. They will have various tests and procedures: Smell tests. They will have several tests that involve smelling different items and answering questions. Questionnaires. They will answer questions about their health, mood, sense of smell, and daily habits. Magnetic resonance imaging (MRI) scans. They will lie on a bed that slides into a tube. Padding will hold their head still. They will smell different odors while in the scanner. Electrobulbogram (EBG). They will wear a soft cap with sensors that measure brain activity. They will smell different odors while wearing the cap. Nasal endoscopy. A flexible tube will be inserted into a nostril to view the inside of the nose. Biopsy. A numbing substance will be sprayed into the nose. Then a scissor-like tool will be used to collect a sample of tissue from one or both nasal passages. Samples of blood, urine, and nasal fluid will be taken.

Observational Digital Biomarker Discovery in Respiratory Virus Challenge Studies

Background: Respiratory viruses circulate throughout the year and around the globe. Wearable and sensor devices, like smartwatches, may be able to help monitor infectious diseases. Researchers want to use them to learn how respiratory viruses affect people in different ways. Objective: To use digital devices to collect data from participants in challenge studies that could indicate subtle changes in health during an infection that might otherwise go unnoticed. Eligibility: Healthy adults who have enrolled, were recently enrolled, or are scheduled to enroll in a challenge study. Design: Participants will stay at NIH for the duration of the challenge study (at least 9 days) and then will have outpatient follow-up visits (2-4). While at NIH, participants will wear a smartwatch at all times. It will record data like temperature, heart rate, breathing rate, and movements. Participants will have a smartphone that records at all times to listen for coughing and changes in voice. Participants will perform tasks every 4 hours during the daytime. They will record themselves coughing, breathing in deeply, and reading aloud. They will take videos of their face. They will play a game to test their reflexes and focus. They will measure their head temperature with their smartwatch. For outpatient visits, participants will use one smartphone and the smartwatch to complete the above tasks. Participants will be sent a smartwatch to wear at home at night to collect additional healthy data. Participation will last the duration of each challenge study, and may range from 10 weeks to 2 years.

Light-based Immunomodulation for Guarding Against Human Respiratory Tract Infections

The purpose of trial is to determine if daily usage of a photobiomodulation device will decrease the incidence of upper respiratory tract infections (URI) due to COVID, influenza or other viruses.The RD-X10 device is handheld, can be self-administered, and has been shown to be safe in invivo studies.

A Study to Evaluate the Safety and Efficacy of CD388 for Prevention of Influenza

The purpose of this study is to evaluate how well CD388 works in preventing symptomatic laboratory-confirmed influenza infections, as compared to placebo, when given as a single dose via 3 subcutaneous (SQ) injections to adult and adolescent participants who are at higher risk of developing influenza complications, and to evaluate the safety and tolerability of CD388, as compared to placebo.

Screening for LID Clinical Studies Unit Healthy Volunteer Protocols

Background: * The Laboratory of Infectious Diseases (LID) Clinical Studies Unit (CSU) enrolls healthy volunteers into clinical studies to study infectious diseases. * Viruses can be highly infectious and contagious. They cause considerable illness in the United States each year and a good example of this is influenza (the flu). The LID CSU performs clinical studies to learn about these viral infections and assist in the development of vaccines and treatments for the infections. These clinical studies include influenza "challenge studies" as well as natural history studies and phase I trials involving vaccines for viruses carried by mosquitos such as Zika or Dengue virus. * In influenza challenge studies studies, doctors expose a person to a flu virus. Then they study the flu through the body's natural healing process. This information will help to find better ways to prevent the flu and may also improve treatments for the flu. * Natural history studies and phase I trials of new vaccines are performed so the researchers can learn how some viral infections occur and if new vaccines are safe and potentially effective in preventing the infections. In some of these studies, participants experience insect bites with special clean (non-infected) insects (such as mosquitos) to better understand the role of insects in these infections. Objectives: \- To screen healthy volunteers for future CSU studies. Eligibility: \- Healthy people between the ages of 18 and 65 Design: * The 3- to 5-hour screening exam includes the following: * Medical history and physical exam * Standard blood tests including pregnancy, Hepatitis B and C, and HIV tests * Standard urine drug testing * Electrocardiogram (ECG) to test heart rhythm and function * Chest x-ray * Eligible volunteers are enrolled in the study for up to 1 year, until they take part in a CSU study or are found to be ineligible to participate. * Volunteers may withdraw from the study pool at any time.

Virological Surveillance of Acute Respiratory Infection in Primary Health Care in Metropolitan France

Every year in the fall and winter, numerous respiratory viruses (such as influenza viruses, SARS-CoV-2 (COVID-19), RSV, rhinovirus, and metapneumovirus) circulate in mainland France, causing acute respiratory infections (ARIs). These viruses can cause epidemics of varying severity, requiring close monitoring to determine their circulation levels and adapt public health measures accordingly. In France, ARI surveillance relies on two networks: the Sentinelles network in primary care and the RENAL network in hospitals. The Sentinelles surveillance is conducted in collaboration with Santé publique France, the National Reference Center for Respiratory Infection Viruses (Institut Pasteur and Hospices Civils de Lyon), and the University of Corsica. As part of the virological surveillance of ARIs, Sentinelles physicians are asked to collect nasopharyngeal swabs or saliva samples from a sample of patients presenting with an ARI during their clinic visits. This surveillance makes it possible to identify respiratory viruses circulating in primary care (general practice and pediatrics), to describe confirmed cases for each of the circulating viruses, and to estimate the impact of each on general practice. This surveillance also allows for the evaluation of the effectiveness of vaccines against influenza and COVID-19.

Clinical Trial to Evaluate the Immunogenicity of an Adjuvanted Influenza Vaccine Among HCP

This randomized, double-blinded trial will assess humoral immune responses to adjuvanted, egg-based quadrivalent influenza vaccines compared to standard dose, egg-based quadrivalent influenza vaccines among healthcare personnel (HCP). The trial will be conducted at two sites in Lima, Peru during 2022 and 2023.

The Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE III) Study

This study will provide novel insight into the effects of repeat influenza vaccination with Flublok and FluMist on the strength and breadth of immune responses to influenza, the mechanisms underlying heterogeneity in vaccine response and vaccine failure, and biological factors that could explain variation in influenza vaccine effectiveness.

B Cell and Antibody Response to Seasonal Influenza Vaccines in Younger and Older Adults

This study will examine how various FDA-approved seasonal influenza vaccine types, used in a manner consistent with their approved use, impact the characteristics of influenza specific antibodies in humans, and how these responses differ based on age and prior immunization history.

Taxifolin/Ergothioneine and Immune Biomarkers in Healthy Volunteers (TaxEr)

The complexities of the immune system make measuring the impact of dietary interventions upon its function challenging. The immune system is highly responsive to environmental influences, including the diet. An individual's diet provides the energy required to mount a strong and protective immune response, the building blocks required for synthesis of immune mediators such as antibodies and cytokines, and can also indirectly affect immune function via changes in the gut microbiome. Immune function varies across the lifecourse, with a well understood decline in immune function with age, resulting in impaired vaccination responses and an increased risk of infections and of severe complications and mortality arising from common communicable diseases such as influenza. This impaired immunity with ageing is known as immunosenescence and this affects both innate and acquired arms of the immune system.

First-in-Human Study of VNT-101: Safety, Tolerability, and Pharmacokinetics

A randomized, double-blind, placebo-controlled Phase 1 study conducted at a single center with approximately 78 healthy adults aged 18-59 years. Part 1 Single Ascending Dose (SAD) will enroll 48 participants into six cohorts (S1-S6) to receive single oral doses of VNT-101 (100-1500 mg) or placebo under fasting or fed (S5 only) conditions. Part 2 Multiple Ascending Dose (MAD) will enroll 30 participants into three cohorts (M1-M3) to receive multiple oral doses of VNT-101 (250-750 mg BID Days 1-5, QD Day 6) or placebo under fasting conditions. Dose escalation in both parts will proceed after Protocol Safety Review Team (PSRT) review. The primary objective for Part 1 is to evaluate the safety and tolerability of single ascending oral (SAD) doses of VNT-101 in healthy adult participants under either fasting or fed conditions. The primary objective for part 2 is to evaluate the safety and tolerability of multiple ascending oral (MAD) doses of VNT-101 in healthy adult participants.

Comparative Immunogenicity of Respiratory Virus Vaccines (CIRV2) Study

CIRV2 is a Phase IV randomized, open-label, trial of FDA-approved COVID-19 and/or influenza vaccines (no more than minimal risk) with longitudinal follow-up. In 2025 CIRV2 will compare immunogenicity and reactogenicity of the recombinant Novavax COVID-19 vaccine and the mRNA Pfizer-BioNTech COVID-19 vaccine.

A Surveillance Study of Susceptibility to Baloxavir Marboxil in Pediatric Participants With Influenza and Transmission of Influenza to Household Contacts

This study consists of two parts: Part A Surveillance and Part B Transmission. The main purpose of Part A is to evaluate the prevalence of pre-dose and treatment-emergent amino acid substitutions in pediatric participants' \<12 years with influenza treated with baloxavir marboxil. Part B will include a subset of Part A participants who have household contacts (HHCs) recruited to the study. Part B will evaluate the incidence of onward influenza transmission from pediatric index participants (IPs) under 5 years of age and those aged 5 to under 12 years, treated with baloxavir marboxil, to their HHCs. Participants will no longer be enrolled to Part B Transmission as per protocol version 3.

CARE-ID: Dynamics of Respiratory Infections in Children and Transmission in Households and Schools

Viral respiratory tract infections are very common in children. They contribute to missed time in school, work disruption for caregivers and can also cause severe illness requiring hospitalization and rarely death. In the 2022-2023, influenza, RSV and SARS-CoV-2 viruses infected a large number of children which strained the pediatric healthcare system in many jurisdictions. Unfortunately, there continues to be limited data on duration of infectiousness and transmission risk of these viruses to inform public health decisions during times when there is significant circulation of these viruses.

Enhancing Maternal Vaccine Knowledge and Uptake: The InTroDuce-Programme Trial

The goal of this InTroDuce-Programme interventional trial aims to test whether a web-based educational program can improve pregnant women's knowledge about Influenza and Tdap vaccinations and increase their intention to get vaccinated in the future. The main questions it aims to answer are: Does the InTroDuce-Programme increase knowledge and future intention of pregnant mothers to get vaccinated against Influenza and Tdap? How does demographic factors, attitudes and barriers affect vaccination decisions among pregnant mothers? Researchers will compare InTroDuce-Programme to standard care (routine antenatal care) to see if InTroDuce-Programme works to improve knowledge and future intention of pregnant mothers to be vaccinated against Influenza and Tdap. Participants will: Receive the web-based educational module (InTroDuce-Programme), which covers the importance, safety, and effectiveness of vaccinations, as well as addressing common concerns. Be followed up one month after the intervention. Answer questionnaires before and after the intervention to measure changes in vaccination knowledge and future intention to get vaccinated

Post-exposure Influenza Prophylaxis in a Hospital Setting

The purpose of this study is to compare the efficacy of 5-day versus 10-day oseltamivir prophylactic treatment in patients who had been exposed to influenza in a hospital setting.

Human Infection Study of H3N2 Influenza in Healthy Adults

This study will examine how the immune system responds to a flu virus (H3N2) during and after infection in health adults aged between 18 and 50 while in an inpatient facility. The study uses a specific flu virus called the H3N2 influenza challenge virus, that was produced specifically for use in clinical research in controlled conditions. From a previous study, mild to moderate symptoms are expected. This is the first time that a flu challenge study has been undertaken in Australia.

A Study on Mucosal Specific IgA Immunokinetics After Administration of Nasal Spray Live Attenuated Influenza Vaccine

Mucosal-specific sIgA antibody GMT;Evaluate the achievement of 2-fold and 4-fold increases in the geometric mean titer (GMT) of specific nasal mucosal sIgA antibodies after vaccination

High vs.Standard Dose Influenza Vaccine in Pediatric Solid Organ Transplant (SOT) Recipients

Influenza virus is a significant pathogen in pediatric solid organ transplant (SOT) recipients. However, these individuals respond poorly to standard-dose (SD) inactivated influenza vaccine (IIV). Recent studies have investigated two strategies to overcome poor immune responses in SOT recipients: (1) administration of high-dose (HD)-IIV compared to SD-IIV and (2) two doses of SD-IIV compared to one dose of SD-IIV in the same influenza season. One study compared HD-IIV vs. SD-IIV in adult SOT recipients and noted that HD-IIV was safe and more immunogenic; however, the median post-transplant period was 38 months. A phase I pediatric study comparing a single dose of HD-IIV vs. SD-IIV was safe with higher immunogenicity, but the study was limited by small sample size and median post-transplant vaccine administration was 26 months. In another phase II trial of adult SOT recipients, two doses of SD-IIV one month apart compared to one-dose of SD-IIV revealed modestly increased immunogenicity when given at a median of 18 months post-transplant. Therefore, these studies lack both evaluation in the early post-transplant period and substantive pediatric populations. Additionally, the administration of two-doses of HD-IIV in the same influenza season has not been evaluated in pediatric SOT recipients. Thus, the optimal immunization strategy for pediatric SOT recipients less than 24 months post-transplant is unknown. In addition, immunologic predictors and correlates of influenza vaccine immunogenicity in pediatric SOT recipients have not been well-defined. The central hypothesis of our proposal is that pediatric SOT recipients 1-23 months post-transplant who receive two doses of HD-quadrivalent inactivated influenza vaccine (QIV) will have similar safety but higher Hemagglutination Inhibition (HAI) geometric mean titers (GMTs) to influenza antigens compared to pediatric SOT recipients receiving two doses of SD-QIV.

GEneRating Mucosal Immunity After INfluenzA Infection and Vaccination in Lung and Lymphoid TissuE

This experimental medicine study aims to compare immune responses in healthy adult volunteers aged 18-55 years against influenza vaccination and infection in the upper and lower respiratory tract, following administration of a live-attenuated influenza vaccine delivered by nasal spray versus influenza A (H3N2) viral challenge.

A Study to Evaluate the Safety and Immunogenicity of Two Doses of DCVC H1 HA mRNA-LNP in Healthy Adults

This is a Phase 1, single-site, comparator-controlled, dosage-escalating study of an intramuscularly administered mRNA-LNP vaccine encoding for DCVC H1 HA in up to 50 adult volunteers aged 18 to 49 years, inclusive. This study is designed to assess the safety and immunogenicity of two doses of DCVC H1 HA mRNA vaccine administered 28 days apart. Eligible participants will be sequentially enrolled into dosage escalation groups (10 mcg, 25 mcg, and 50 mcg). A separate group of 10 participants will receive one dose of the licensed quadrivalent influenza vaccine (IIV4). Enrollment of participants into the IIV4 group is limited to when the vaccine is available for a given year. Concurrent enrollment of the IIV4 group and any pre-specified study product group or groups may present logistical challenges due to the availability of the IIV4 vaccine and may preclude enrollment of all study participants prior to the subsequent off-season. Participants receiving IIV4 will be followed for safety but only their immune responses will be compared to those of participants receiving DCVC H1 HA mRNA vaccine. Dosing of DCVC H1 HA mRNA vaccine will commence at the lowest dose (10 mcg) and only escalate to the next highest dose if safety concerns are not identified. For each DCVC H1 HA mRNA vaccine dosing group, the first two participants enrolled will be considered the sentinel subgroup. After the two participants in the Low Dose sentinel subgroup are enrolled and given their first vaccination, enrollment and subsequent vaccinations in that dosing group will then be stopped until Day 3. This review will be conducted by a Safety Review Committee (SRC). If no halting criteria are met, the SRC will allow administration of the second dose for the sentinel subgroup and continued enrollment of the remaining 8 Low Dose Group participants (expanded subgroup) to complete enrollment of 10 participants. In order for a timely receipt of a second dose of study product on Day 29, SRC review and approval must occur prior to Study Day 28 for the first sentinel participant in the Low Dose Group. After the Low Dose Group enrollment is completed and both doses have been administered, enrollment will be stopped pending SRC review. After all participants in the Low Dose Group have completed the Day 36 visit, the SRC will review the clinical laboratory, reactogenicity, and adverse event information through the Day 36 visit for all Low Dose Group participants that received two doses. Approval by the SRC will allow dose escalation and initiation of enrollment of the Medium Dose Group sentinel subgroup. The Medium and High Dose sentinel and expanded groups will be enrolled as described above for the Low Dose sentinel and expanded groups, respectively, with the High Dose expanded subgroup enrolling up to 18 individuals. The primary objective of this study is to assess the safety of two doses of DCVC H1 HA mRNA Vaccine administered intramuscularly in healthy adults (18-49 yrs) at dosage levels of 10 mcg, 25 mcg, and 50 mcg.

First-in-human Study to Assess the Safety, Tolerability and Immunogenicity of the Adjuvanted Universal Influenza Vaccine fH1/DSP-0546LP

This study is a single center, randomized, double-blind, placebo-controlled, dose-finding, FIH, Phase 1 study to assess the safety, tolerability, and immunogenicity of the adjuvanted Universal Influenza Vaccine (fH1/DSP-0546LP) after IM administrations in healthy adults.

The Interaction Between Mucosal Microbiota Colonization and the Immune Response to an Intranasal Influenza Live Attenuated Vaccine

This is a single-center, randomized, open-label trial designed to explore the interaction between mucosal microbiota colonization in the nasal cavity and gut and the immune response to an intranasal live attenuated influenza vaccine (LAIV). The study plans to enroll 200 children and adolescents aged 6-17 years, with approximately 50% in the 6-11 years age group and 50% in the 12-17 years age group. Participants and their guardians must be able and willing to comply with the clinical trial protocol and provide informed consent. Eligible participants will be randomly assigned in a 1:1 ratio, stratified by age groups, to either the immediate vaccination group or the delayed vaccination group. Nasal swabs will be collected for all participants of both the immediate vaccination group or the delayed vaccination group after randomization for the detection of nasal and gut microbiota. Then, the immediate vaccination group will receive one dose of 0.2 mL of LAIV 28 days after randomization, while the delayed vaccination group will receive one dose of 0.2 mL of LAIV 56 days after randomization. Blood and mucosal samples (nasal stool) will be collected on the day before vaccination and on 28 days after vaccination for humoral and mucosal immunogenicity analysis. Moreover, the occurrence of adverse events within 28 days after vaccination will be collected.

H5N1 Milk Detection Study

The purpose of this study is to determine whether drinking pasteurized milk (milk heated to kill harmful germs) that contains inactive particles of a flu virus called A(H5) could lead to the detection of the virus in the nose or throat. Inactive particles are not capable of causing disease. The results will help the Centers for Disease Control and Prevention (CDC) better understand how milk consumption could affect flu surveillance. Investigators also want to see if the body produces antibodies in response to this milk consumption.