Clinical Research Directory

Viromes in Infants Presenting With a Septic Syndrome

Fever in infants younger than 3 months is a common reason for emergency department visits and is associated with a significant risk of serious bacterial infections. Because it is difficult to distinguish bacterial from viral infections at presentation, management is often aggressive and includes invasive procedures, hospitalization, and empiric antibiotic therapy. Despite advances in molecular diagnostics, the etiology of fever remains unidentified in a substantial proportion of cases. This study aims to assess the presence of pathogenic viruses in respiratory and intestinal samples from febrile infants younger than 3 months compared with afebrile controls, and to explore associations with clinical, biological, environmental, and socio-economic factors

Trial of Scheduled Versus Treatment Administration of Donor-Derived Viral Specific T-cells for Viral Infections After Stem Cell Transplant

The purpose of this research study is to learn more about the use of viral specific T-lymphocytes (VSTs) to prevent or treat viral infections that may happen after allogeneic stem cell transplant. Allogeneic means the stem cells come from another person. VSTs are cells specially designed to fight viral infections that may happen after a stem cell transplant (SCT). Stem cell transplant reduces the body's ability to fight infections. Viral infections are a common problem after transplant and can cause significant complications. Moreover, treatment of viral infections is expensive and time consuming, with families often administering prolonged treatments with intravenous anti-viral medications, or patients requiring prolonged admissions to the hospital. The medicines can also have side effects like damage to the kidneys or reduction in the blood counts, so in this study the investigators are trying to find a better way to treat these infections.

Adoptive T Lymphocyte Administration for Chronic Norovirus Treatment in Immunocompromised Hosts

This is a Phase I dose-escalation study to evaluate the safety of norovirus -specific T-cell (NST) therapy for chronic norovirus infection in participants following hematopoietic stem cell transplantation (HSCT) or who are immunocompromised due to PID and have not undergone HSCT, or Solid Organ Transplant (SOT) recipients.

Effects of Mouthrinse on the Microbiome of the Oral Cavity and GI Tract

The purpose of this research study is to identify the effects of 2 over-the-counter mouthwashes on bacteria and 3 viruses in the participant's mouth and gut. The participant will be randomly allocated to rinse their mouth twice daily either with Listerine mouthwash, Lumineux Oral Essentials mouthwash, or water. The overall duration of the study will be approximately 180 days and will include approximately 5 visits and 15-30 minutes for each visit with a total of approximately 2.5 hours of your time. Additionally, fecal matter will also be collected in some subjects using a commercial collection kit.

Third Party Viral Specific T-cells (VSTs)

The purpose of this study is to demonstrate that viral specific T-cells (a type of white blood cell) can be generated from an unrelated donor and given safely to patients with viral infections.

Donor-Derived Viral Specific T-cells (VSTs)

In this research study, the investigators want to learn more about the use of donor-derived viral specific T-cells (VSTs) to treat viral infections that occur after allogeneic stem cell transplant. A viral specific T cell is a T lymphocyte (a type of white blood cell) that kills cells that are infected (particularly with viruses). Allogeneic means the stem cells come from another person. These VSTs are cells specially designed to fight the virus infections that can happen after a bone marrow transplant. The investigators are asking people who have undergone or will undergo an allogeneic stem cell transplant to enroll in this research study, because viral infections are a common problem after allogeneic stem cell transplant and can cause significant complications including death. Stem cell transplant reduces a person's ability to fight infections. There is an increased risk of getting new viral infections or reactivation of viral infections that the patient has had in the past, such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus (ADV), BK virus (BKV), and JC virus. There are anti-viral medicines available to treat these infections, though not all patients will respond to the standard treatments. Moreover, treatment of viral infections is expensive and time consuming, with families often administering prolonged treatments with intravenous anti-viral medications, or patients requiring prolonged admissions to the hospital. The medicines can also have side effects like damage to the kidneys or reduction in the blood counts, so in this study the investigators are trying to find an easier way to treat these infections.

School Inner City Air Study

The goal of this randomized clinical trial is to test the efficacy of high efficiency particulate air (HEPA) cleaners in reducing respiratory viral exposure and infections in elementary school classrooms. Classrooms will be randomized to active vs. sham HEPA cleaners. The main questions it aims to answer are: * Do classroom HEPA cleaners reduce exposure to viruses? * Do classroom HEPA cleaners reduce student and teacher infections? * Do classroom HEPA cleaners reduce infections in family members?

Rapid Diagnosis of Viral Acute Respiratory Infection to Decrease Unnecessary Antibiotic Utilization in the Emergency Department (RADIATE)

The study titled " The Effect of Definitive Identification of Viral Etiology in Emergency Department Patients with Acute Respiratory Infection on Antibiotic Utilization (RADIATE)" aims to investigate the effectiveness of a rapid diagnostic approach in reducing unnecessary antibiotic use in the emergency department (ED) for patients presenting with acute respiratory illness (ARI) due to a virus. Using a prospective design, eligible participants are individuals who visit the ED with complaints related to acute respiratory illness. The study will employ a single-arm consecutive enrollment approach. The intervention involves the implementation of a rapid point-of-care multiplex polymerase chain reaction (PCR) test to promptly identify the viral cause of the infection. By utilizing a rapid diagnostic tool to identify viral etiology, the study aims to provide healthcare professionals in the ED with more accurate information to guide treatment decisions. Ultimately, the goal is to decrease the unnecessary use of antibiotics for ARI's due to a virus, which has several negative outcomes including promotion of antibiotic resistance, exacerbating ED length of stay and encouraging unnecessary additional diagnostic tests.

Viral Specific T-cells for Treatment of Viral Infections After Solid Organ Transplant

The purpose of this research study is to learn more about the use of viral specific T-lymphocytes (VSTs) to treat viral infections that may happen after solid organ transplant (SOT). VSTs are cells specially designed to fight viral infections that may happen after a solid organ transplant. These cells are created from a blood sample collected from the study participant. Solid organ transplant and the use of immunosuppressive medications reduces the body's ability to fight infections. Viral infections are a common problem after transplant and can cause significant complications. Reduction of immunosuppression may put the organ at risk of rejection. Moreover, treatment of viral infections is expensive and time consuming, with families often administering prolonged treatments with intravenous anti-viral medications, or patients requiring prolonged admissions to the hospital. The medicines can also have side effects like damage to the kidneys or reduction in the blood counts, so in this study the investigators are trying to find a better way to treat these infections and minimize complications.

TETRAVI Multivirus CTL for Treatment of EBV, CMV, Adenovirus, and BK Infections Post Allogeneic SCT.

The purpose of this study is to use VSTs (virus-specific T cells) from a donor that is a partial HLA (human leukocyte antigen) match with the patient to treat viral infections after an allogeneic hematopoietic stem cell transplant (HSCT). These cells may also have value in CAR-T recipients who have received a product that depletes virus specific T cells. The patient must have had a myeloablative or non-myeloablative allogeneic HSCT using either bone marrow, single/double umbilical cord blood, or peripheral blood stem cells (PBSC) or CAR T cell product targeting an antigen expressed on virus specific T cells. After a transplant, while the immune system grows back, the patient is at risk for infection. Some viruses can stay in the body for life and are normally controlled by a healthy immune system, but if the immune system is weakened, like after a transplant, they can cause life threatening infections. He/she must have had an infection with one or more of the following viruses -Epstein Barr virus (EBV), cytomegalovirus (CMV), adenovirus (AdV), Human polyomavirus type I (BKV), and human polyomavirus type II (JCV)- that has persisted or recurred despite standard therapy. In this study, the investigators want to use white blood cells that have been trained to treat viral infections. In an earlier study the investigators showed that treatment with such specially trained T cells has been successful when the cells are made from the transplant donor. However as it takes 1-2 months to make the cells, that approach is not practical for patients who already have an infection. In a subsequent study, the investigators were able to create multivirus-specific T cells (VSTs) from the blood of healthy donors and created a bank of these cells. The investigators then successfully used these banked cells to treat virus infections after a stem cell transplant. In this study the investigators have further modified their production method to decrease the potential side effects and the investigators want to find out if they can use these banked VSTs to fight infections caused by the viruses mentioned above.

A Rhinovirus Challenge Study to Investigate Exacerbations and Immune Responses in Bronchiectasis

The goal of this study is to determine if viral infection with the common cold leads to an exacerbation in participants with bronchiectasis. The investigators will compare the participants with bronchiectasis to a group of healthy participants. The main questions it aims to answer are: * Does viral infection with the common cold lead to an exacerbation in bronchiectasis? * Does the immune response differ to that of a healthy participant? Participants will attend for a screening visit to see if they are eligible. All participants who are eligible and have consented to take part will have baseline investigations done including blood tests and a bronchoscopy. They will be given a spray of a virus that causes the common cold into their nose. They will then be followed up over the next 6 weeks with some of the following procedures at each study visit; spirometry, nasosorption, nasal lavage, nasal brushing, blood test, sputum collection and a bronchoscopy. Participants will be asked to keep a daily record of their symptoms throughout the study.

REVIVe: Frailty, Rehabilitation, and Outcomes in Critically Ill Adult and Pediatric Survivors of COVID-19 or ARI

Background: Many adults and some children with COVID-19 or acute respiratory infection become critically ill and need advanced life support in the Intensive Care Unit (ICU). Frailty is a medical condition of reduced function and health. Adults with frailty have a lower chance of surviving critical illness. The investigators are still learning about critically ill adults with COVID-19 or acute respiratory infection, and do not have much information on how frailty affects outcomes in critically ill children, with or without COVID-19 or acute respiratory infection. Rehabilitation can help survivors of COVID-19 or acute respiratory infection by improving strength and improve quality of life (QOL). Objectives: The main goal of this research study is to see if patients with frailty have a lower chance of surviving COVID-19 or acute respiratory infection critical illness and more health problems after survival than patients without frailty. The investigators will also study the types of rehabilitation received by patients with COVID-19 or acute respiratory infection. Methods: The investigators will include adults and children with COVID-19 or acute respiratory infection who are admitted to the ICUs that participate in the study. The investigators will gather data about each patient, including before and during their illness. Outcomes: The investigators will collect level of frailty, function, and types of therapy, or rehabilitation received by patients. In adults, the investigators are most interested in learning if frailty influences mortality, or death. In children, the investigators are most interested in whether children with COVID-19 or acute respiratory infection critical illness are more likely to develop frailty. The investigators will also study post-hospital discharge location in survivors (e.g., home, rehabilitation). Relevance: The COVID-19 pandemic is a global public health crisis. It is critical to understand how COVID-19 and other acute respiratory infection critical illness affects groups of people who are at higher risk, and the impact on outcomes that are important to patients, like functioning and QOL. The results will help policy makers plan post-hospital services for survivors, help healthcare workers understand the importance of rehabilitation practice for patients with COVID-19 or acute respiratory infection, and help researchers develop treatments to improve QOL after COVID-19 or acute respiratory infection.

Adoptive Cord Blood Immunotherapy for EBV, CMV, BKV and Adenovirus Reactivation/Infection or Prophylaxis

This Phase I-II dose-finding trial to determine the optimal dose of intravenous (IV) injection dose of donor-derived cytotoxic T lymphocytes (CTLs) specific for CMV, EBV, BKV and Adenovirus. A maximum of 36 patients will be treated in up to 18 cohorts each of size 2, with the first cohort treated at the lowest dose level 1, all successive doses chosen by the EffTox method, and no untried dose level skipped when escalating. The scientific goal of the trial is to determine an optimal IV-CTL cell dose level among the three doses 1.0x107cells/m2, 2 x107cells/m2 and 5x107cells/m2., hereafter dose levels 1, 2, 3. Dose-finding will be done using the sequentially adaptive EffTox trade-off-based design of Thall et al.

Lung Immune Challenge Study: Controlled Exposure to Inhaled Resiquimod (R848)

Respiratory viral infections can be a cause of significant illness, particularly in vulnerable individuals as seen in the COVID-19 pandemic. An underactive or overactive immune response can lead to ineffective resolution of inflammation after an infection, especially in people with airway diseases such as asthma. A better understanding of immune responses to infection that does not rely on cell or animal models is crucial to help develop better treatments for lung inflammation. An established method of studying inflammation in humans is through careful and controlled exposure (or "challenge") with a mimic of a virus to simulate an infection in a similar manner to that of a virus, but with the advantage of not causing an infection. The investigators have already developed a well-tolerated mimic of human viral infection using a sterile substance called Resiquimod (or R848). Since it does not contain living organisms there is no possibility of being infected. This has been used previously as a nasal spray to cause a mild short-lived inflammation that mimics a mild cold. This has been used safely in a range of people of different ages including those who have asthma. There are differences however in how the nose and lungs respond to viral infections. This is particularly true in those with airway diseases such as asthma, who have cells in the airways of their lungs that respond in a different way to inflammatory triggers (such as viruses). The current study aims to build on previous research by developing a new approach of studying inflammation in the lungs using a small volume of Resiquimod. This will be done by gently inhaling a fine mist through a mouthpiece into the lungs. Blood and phlegm samples would then be collected to assess inflammation and how well people tolerate the procedure.

Treatment of Refractory BK Infections With Related Donor BK Specific Cytotoxic T-cells (CTLs)

BK cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine Capture System will be safe and effective in decreasing specific viral load in children, adolescents and young adults (CAYA) with refractory BK infection post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT) or with primary immunodeficiencies (PID).

Retrospective Observational Study on Infective Complications and Outcome of Patients With ALL Treated With INO

The goal of this observational study is to learn about infectious complications in patients affected by B-cell acute lymphoblastic leukemia treated with inotuzumab-ozogamicin (INO). The main question it aims to answer is: • incidence of infectious complications (bacterial, fungal, viral) in patients receiving inotuzumab ozogamicin up to 60 days after the end of treatment

COMPArative Study of the Consequence on innaTe Immune Response du to Bacterial or Viral Infection in Patients Admitted to Intensive Care Unit

Patient admitted in intensive care unit (ICU) for acute infection whether it be viral or bacterial had major impairment of the immune response. One hallmark of the immune impairment is presence of immature granulocyte (IG) in blood. Depend of initial trigger (virus or bacteria) concentration, phenotype and function of IG seems to be different. In this prospective trial, immature granulocytes will be analyzed in depth in immunocompetent patients hospitalized in the intensive care unit for an acute viral or bacterial infection.

Isotonic Saline for Children With Bronchiolitis

The goal of this randomized clinical trial is to investigate the optimal supportive treatment of bronchiolitis in infants from 0-12 months of age. The main question\[s\] it aims to answer are: * To investigate whether isotonic saline should be used as supportive treatment for children with bronchiolitis, and if so, identify the optimal route of administration. The primary outcome is duration of hospitalization. * To investigate the current epidemiology of the viral pathogens causing bronchitis in children in Denmark, and to assess whether children infected with specific pathogens might benefit from treatment with isotonic saline. The children are randomized after inclusion through computer randomization to one of the 3 arms in the study: 1. Nebulized isotonic saline 2. Nasal irrigation with isotonic saline 3. No treatment with saline The investigators will compare treatment with saline (both methods) with no treatment, and the investigators will also compare the two methods of delivery of saline (nebulized vs. nasal irrigation).