Clinical Research Directory

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.

Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES)

The Hyper IgE Syndromes (HIES) are primary immunodeficiencies resulting in eczema and recurrent skin and lung infections. Autosomal dominant Hyper IgE syndrome (AD-HIIES; Job's syndrome) is caused by STAT3 mutations, and is a multi-system disorder with skeletal, vascular, and connective tissue manifestations. Understanding how STAT3 mutations cause these diverse clinical manifestations is critical to our complete understanding of bone metabolism, bronchiectasis, dental maturation, and atherosclerosis. Bi-allelic mutations in DOCK8 cause a combined immunodeficiency previously described as autosomal-recessive Hyper IgE syndrome. These individuals suffer from extensive viral infections as well as have a high incidence of malignancy and mortality. The pathogenesis of this disease and long-term natural history is being investigated. Therefore, we seek to enroll patients and families with a confirmed or suspected diagnosis of HIES syndrome for extensive phenotypic and genotypic study as well as disease management. Patients will be carefully examined by a multidisciplinary team and followed longitudinally. Through these studies we hope to better characterize the clinical presentation of STAT3-mutated HIES, DOCK8 deficiency and other causes of the hyper IgE phenotype, and to be able to identify further genetic etiologies, as well as understand the pathogenesis of HIES. We seek to enroll 300 patients and 300 relatives....

Bevacizumab in Adults With Recurrent Respiratory Papillomatosis (RRP)

Background: Recurrent respiratory papillomatosis (RRP) is a rare disease that causes wart-like growths in the airways. These growths come back when removed; some people may need 2 or more surgeries per year to keep their airways clear. Better treatments are needed. Objective: To see if a drug called bevacizumab can reduce the number of surgeries needed in people with RRP. Eligibility: People aged 18 and older with recurrent RRP; they must need surgery to remove the growths in their airways. Design: Participants will be screened. Their ability to breathe and speak will be evaluated. They will have an endoscopy: a flexible tube with a light and camera will be inserted into their nose and throat. They will have a test of their heart function and imaging scans of their chest. Participants will have surgery to remove the growths in their airways. Bevacizumab is given through a small tube placed in a vein in the arm. After the surgery, participants will receive 11 doses of this drug: every 3 weeks for 3 doses, and then every 6 weeks for 8 more doses. They will come to the clinic for each dose; each visit will be about 8 hours. Tissue samples of the growths will be collected after the second treatment; this will be done under general anesthesia. Participants may undergo apheresis: Blood will be drawn from a needle in an arm. The blood will pass through a machine that separates out the cells needed for the study. The remaining blood will be returned to the body through a second needle. Follow-up will continue for 1 year after the last treatment....

A Phase I Study of Mozobil in the Treatment of Patients With WHIMS

Background: * WHIMS (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis Syndrome) is caused by various genetic changes that increase the activity of the chemokine receptor, CXCR4. Excessive function of this receptor causes mature neutrophils (part of the white blood cells) to be retained within the bone marrow rather than being released to the blood and is one of the causes of severe inherited neutropenia (low white blood counts). In neutropenia, the body is less able to fight off infection. Patients with WHIMS usually are at risk for skin, soft tissue, sinus, and lung infections, which can result in loss of hearing, teeth, and lung function. * Current treatment for WHIMS consists of regular injections of a white blood cell growth stimulating medication called granulocyte colony stimulating factor (G-CSF), and supplemental immunoglobulin (antibody). These therapies are expensive, nonspecific, have significant side effects and toxicities, and do not fully correct all problems, especially warts and cancers related to human papillomavirus (HPV). * A drug called Mozobil has been approved for use in combination with G-CSF to increase the number of stem cells that can be collected prior to bone marrow transplantation. Mozobil may offer a specific and well-tolerated new treatment for WHIMS and other syndromes characterized by neutropenia. Objectives: * To evaluate whether Mozobil is safe and effective to treat neutropenia (low white blood cell count) in patients with WHIMS. * To determine an appropriate treatment dose of Mozobil, within currently approved dosage levels. Eligibility: \- Individuals between 18 and 75 years of age who have been diagnosed with WHIMS and have a history of severe infections. Design: * Potential participants will undergo a screening with a medical history, physical examination, questionnaire, heart and lung function scans, and blood and urine samples. Tests will also be done for hepatitis B and C virus, and human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS), as well as to check neutrophil function. * Patients who are being treated with G-CSF will stop injections for 2 days before being admitted to the National Institutes of Health (NIH) Clinical Center. * Patients may participate in a Dose Escalation study and receive increasing doses of Mozobil over 5 days of treatment until their white blood cell count improves sufficiently or the maximum approved dose is reached. Blood samples will be taken regularly throughout the treatment process. Patients will then receive an additional dose of Mozobil at the maximum approved dose or the dose sufficient to cause improvement, before restarting the G-CSF injections. * Patients may also participate in a long-term Chronic Dosing study and receive Mozobil once or twice a day for up to a maximum of 60 months.

Single Versus Double Drains in the Axillary and Pectoral Regions After Modified Radical Mastectomy

Normally, after this surgery, skin is stitched in the usual simple way, with no quilting, and two drains are put in to remove serosa, one under the arm and one on the chest. In this study, the investigator will use a different type of stitch called a quilting stitch, which helps stick the skin to the chest muscle so there is less serosa collection. The investigator will compare two groups: * Group A: Quilting stitches with two drains (one under the arm and one on the chest). * Group B: Quilting stitches with one drain only (under the arm).

Evaluation and Assessment for Communicable Diseases in Migrants Hosted in Reception Centers

A single-centre, non-profit experimental clinical trial. The aim of the study is to estimate the prevalence of a range of infections and infectious diseases in a cohort of asylum seekers staying in initial reception centres, who have been in Italy for at least 2 months but no more than 36 months. The infections of interest are: latent tuberculosis and active tuberculosis, HIV, HBV, HCV, syphilis, strongyloidiasis, schistosomiasis, filariasis, and intestinal helminthiasis.

Analysis of the Virtual Acute Care at Home Experience

The purpose of this study is to examine the implementation, intervention effectiveness, and dissemination of a digital acute care delivery model for improving selected health outcomes in the Hospital at Home population.

Light-Activated Antimicrobial Therapy to Prevent Surgical Site Infections

This is a Phase 3 multi-center, group-randomized, crossover trial to compare nasal antimicrobial photodisinfection therapy (aPDT) with standard of care for prevention of surgical site infections in patients undergoing major elective, urgent, or emergent surgeries in a hospital setting. The main outcomes are to: 1. compare the efficacy, and 2. estimate the safety of applying nasal (aPDT) before surgery in reducing the incidence of SSIs within the initial 30 days after surgery compared to standard of care (SOC). Participants in the intervention group will receive aPDT prior to surgery on the day of surgery. Participants in the control group will receive standard of care surgical site prevention measures prior to surgery.

Healing Electroceutical Dressing for the Recovery of Open Wounds (HERO)

The goal of this clinical trial is to determine whether the wireless electroceutical dressing (WED) called PowerHeal™ Bioelectric Bandage, improves care of infected wounds by clearing the infection and helping the wound heal better. The main hypotheses it aims to answer are: 1. WED promotes wound closure, as determined by wound area measurement 2. WED manages wound infection in civilian and military wounds in Ukraine, as determined by clinical assessment of wound infection by measuring the numbers and types of relevant microbes. Researchers will compare to see if PowerHeal™ Bioelectric Bandage the dressing used in the SOC group Participants will get their dressings changed per the protocol, wound image and swab will be taken.

Light-Activated Antimicrobial Therapy to Prevent Surgical Site Infections - Canada

This is a Phase 4 multi-center, group-randomized, crossover trial to compare nasal antimicrobial photodisinfection therapy (aPDT) with standard of care for prevention of surgical site infections in patients undergoing major elective, urgent, or emergent surgeries in a hospital setting. The main outcomes are to: 1. compare the efficacy, and 2. estimate the safety of applying nasal (aPDT) before surgery in reducing the incidence of SSIs within the initial 30 days after surgery compared to standard of care (SOC). Participants in the intervention group will receive aPDT prior to surgery on the day of surgery. Participants in the control group will receive standard of care surgical site prevention measures prior to surgery.

Collection of Blood Samples for New Diagnostic Devices 2

To research and develop new state of the art diagnostic biomarkers on the LumiraDx Platform that are comparable to the approved gold standard reference methods and will radically enhance clinicians and patients ability to monitor health conditions and improve outcomes by delivering the results near patient at the point of care.

L-citrulline to Improve Adverse Outcomes in Admitted Children (EChiLiBRiST, Clinical Trial 2, Inpatients)

In low and middle-income countries, children admitted to hospital are not similarly ill, and do not all have a comparable prognosis. In fact, understanding at first encounter their risk of developing adverse outcomes (including mortality) could allow a more focused management and the tailoring of specific interventions to decrease in hospital mortality, and post discharge adverse longer-term outcomes. This clinical trial, part of the EChiLiBRiST larger project ("Development and validation of a quantitative point-of-care test for the measurement of severity biomarkers to improve risk stratification of fever syndromes and enhance child survival") has the two-fold objective of: 1. Assessing whether a POINT-OF-CARE rapid triaging test (PoC RTT) based on the quantitative measurement at the bedside of the "prognostic" biomarker sTREM-1 (soluble-triggering receptor expressed on myeloid cells 1) can reliably identify those admitted children with a higher risk of adverse outcomes; and 2. Assessing whether the therapeutic intervention (the L-arginine precursor, L-Citrulline, key in the nitric oxide biosynthesis), administered orally for 28 days to those children aged 1-\<60 months identified as "moderate-to-high risk" by the prognostic biomarker can improve outcomes as compared to those receiving an indistinguishable placebo. This second objective will be assessed in a prospective multi-country, multi-site, individually randomised, two-arm, placebo-controlled, double blind clinical trial involving \~888 children 1-\<60m of age admitted to hospital and determined to be at high risk of adverse outcomes by their baseline sTREM-1 levels. The trial will compare the efficacy of a twice-daily dose of L-citrulline syrup vs placebo (200-300mg/kg/day depending on weight-band; for 28 days) in reducing adverse outcomes in children with severe disease. The trial will be running independently but in parallel in two high-mortality settings in Mozambique and in Ethiopia.

A Cohort Study on Anti-microbial Stewardship in PICU

Appropriate antimicrobial therapy is essential to ensuring positive patient outcomes. Inappropriate or suboptimal utilization of antibiotics can lead to increased length of stay, multidrug-resistant infections, and mortality. Critically ill intensive care patients are at risk of antibiotic failure and secondary infections associated with incorrect antibiotic use. Initiating effective therapy for infections based upon patients' risk factors, collection of appropriate cultures, daily evaluation of clinical status, and laboratory data, including antibiotic time outs, and shortened duration of therapy are ways to improve patients outcomes. Antimicrobial stewardship teams can assist ICU providers in managing and implementing these tactics. ICUs would benefit from employing empiric guidelines for antibiotic use, collecting appropriate specimens and implementing molecular diagnostics, optimizing the dosing of antibiotics, and reducing the duration of total therapy.

Bern, Get Ready (BEready) Cohort Study for Pandemic Preparedness

The BEready project aims to find out how people in the Canton of Bern can be helped to be more prepared for the next pandemic. BEready wants to understand how infections spread among people as well as between people and animals. BEready wants to find out how social and environmental factors can influence the transmission or catching of infectious diseases. BEready wants to better understand how households and their pets in the Canton of Bern were and continue to be affected by the coronavirus disease 2019 (COVID-19).

PO vs IV Antibiotics for the Treatment of Infected Nonunion of Fractures After Fixation

This is a Phase III clinical randomized control trial to investigate differences between patient with an infected nonunion treated by PO vs. IV antibiotics. The study population will be 250 patients, 18 years or older, being treated for infected nonunion after internal fixation of a fracture with a segmental defect less than one centimeter. Patients will be randomly assigned to either the treatment (group 1) PO antibiotics for 6 weeks or the control group (group 2) IV antibiotics for 6 weeks. The primary hypothesis is that the effectiveness of oral antibiotic therapy is equivalent to traditional intravenous antibiotic therapy for the treatment of infected nonunion after fracture internal fixation, when such therapy is combined with appropriate surgical management. Clinical effectiveness will be measured as the primary outcome as the number of secondary re-admissions related to injury and secondary outcomes of treatment failure (re-infection, nonunion, antibiotic complications) within the first one year of follow-up, as defined by specified criteria and determined by a blinded data assessment panel. In addition, treatment compliance, the cost of treatment, the number of surgeries required, the type and incidence of complications, and the duration of hospitalization will be measured.

A Follow-up Trial of GBS-NN/NN2 Vaccine in Healthy Pregnant Women

The main objective of the study is to evaluate the persistence of the immunoglobulin G (IgG) antibody responses, specific to Alpha-like protein CN (AlpCN), Ribosomal Protein N (RibN), Alpha-like protein 1N (Alp1N), and Alpha-like protein 2 and 3 (Alp2-3N), after a primary vaccination with GBS-NN/NN2 in all participants.

Personalized Immunological Score for the Prediction of Severe Infectious Events in Immunocompromised Patients and Tailored Management (PERISCOPE)

Transplants have improved clinical conditions for many patients with haematological diseases and end-stage organ diseases. However, immunosuppressive therapies that are necessary for avoiding organ rejection have a crucial impact in the occurrence of opportunistic infections. Despite the development of effective antimicrobial agents, infectious diseases are still related to mortality and morbidity in immunocompromised patients. Immune function assays can be adopted for monitoring T-cell function and eventually modify immunosuppression. Given the inverse relationship between cellular immune reconstitution and risk of infection, many transplant centers prospectively monitor immune recovery post-transplant. Some basic methods are useful, including white blood cells and T-lymphocyte subsets count. Given the complexity of immune responses required to resolve infections, functional assays are necessary and the only available FDA-approved one is Cyclex-Immuknow. Viral infections are common in patients with T-cell deficiencies and are of particular concern in those receiving high dose steroids. Opportunistic infections are common during the period of highest immunosuppression while community acquired infections, including fungal and respiratory viruses infections, have to be considered in the long-term period. Reduced CD4+ and CD8+ T-lymphocyte counts correlate with risk of opportunistic infection, including human cytomegalovirus (HCMV). Moreover, a decrease in human Rhinovirus (HRV) load in pediatric hematopoietic stem cell transplant recipients (HSCTRs) was associated with a significant increase in T-CD4+, T-CD8+ and NK lymphocytes, suggesting that cellular immunity have a crucial role in viral clearance and infectious control. A recent study showed that poor NK-cell cytotoxic activity is associated with increased risk for severe infections in kidney-graft recipients, suggesting that assessment of NK-cell function may be used as a predictor of infection in immunocompromised patients. Moreover, it has been recently reported that NKG2C genotype influences receptor function and NKG2C+ NK cell number in HCMV seropositive subjects. In detail, NKG2C genotype is significantly associated with HCMV viremia frequency and related disease after lung transplant and with symptomatic CMV infection after kidney transplant. Beside the use of non-specific immunological markers, the lack of standardized quantitative measures of protective immune functions specific for different opportunistic pathogens represents a challenge for clinicians. Overall, a comprehensive approach based on the use of combined non-specific and pathogen-specific immune assays may help in the definition of a composite immune risk profile of immunocompromised patients. The ultimate goal of this research is the definition of algorithms of infectious risk in immunocompromised patients, leading to a more adherent administration of immunosuppressive and antimicrobial therapies as well as to a personalized strategy of patients' management. Moreover, the design of new immunological assays that can be standardized and used in the clinical practice will be obtained. Currently, even if an immunological monitoring of immunocompromised patients is recommended, no standardized assays and protocols are available, especially for the use of antigen-specific or functional assays. The introduction of diagnostics algorithms will be useful for the stratification of patients at high risk of infections that will be monitored more frequently in order to prevent severe infections. Similarly, the administration of immunosuppressive drugs or ad hoc therapies might be tailored according to the risk of infections or complications. Objective is to identify a composite immune score measured either before or one month after transplant/chemotherapy able to define the risk for clinically significant infections (e.g. infections requiring antimicrobial therapy or hospitalization) during the following three months. Primary endpoint: To identify a composite immune score measured either before or one month after transplant/chemotherapy able to define the risk for clinically significant infections (e.g. infections requiring antimicrobial therapy or hospitalization) during the following three months. Secondary endpoints: * To evaluate the prognostic effect of the immunological score measured before or at first month after transplant/chemotherapy on the risk of severe infection during the following 6-12 months * To compare the role of the composite immunological score with specific assays against each pathogen. * To develop simple and rapid assays using whole blood to evaluate specific pathogen responses

Effects of an Infant Formula and follow-on Formula Containing Bio-active Ingredients on Growth, Tolerance and Infections

In this clinical trial, the growth (weight for age), product tolerance (product intake, comfort) and infection-related symptoms of healthy infants consuming an IF and FOF containing bio-active ingredients will be evaluated and compared to a group of infants consuming a standard IF and FOF.

Bacillus Cereus Invasive Infections in Preterm Neonates Hospitalized in French Hospitals

Background. Bacillus cereus group (Bc) comprises twenty-six closely related species of spore-forming environmental bacteria. Recently, increased sepsis and septic shock caused by Bc were reported in preterm neonates (PN), and the mortality rate can reach up to 30%. Using Whole Genome Sequencing (WGS) increasingly used to characterize Bc strains, The team aimed to determine an accurate identification to the species level of the strains involved in Bc invasive infections in preterm neonates in France and study their virulome profile.Methods. The team performed WGS for 40 neonate clinical strains responsible for invasive infections in PN. A screening of virulence genes was performed to characterize strains associated with poor prognosis. Clinical data were collected and all clinical and genomic findings were analyzed for risk factors for death. "

Advancing Health Information Exchange (HIE) During Inter-hospital Transfer (IHT) to Improve Patient Outcomes

Sub-optimal transfer of clinical information during inter-hospital transfer (IHT, the transfer of patients between acute care hospitals) is common and can lead to patient harm. To address this problem, the investigators will use key stakeholder input to refine and implement an interoperable health information exchange platform that integrates with the electronic health record and improves the reliability of and access to necessary clinical information in three use cases involving transfer of patients between sending and receiving hospitals with varying levels of affiliation and health record integration. The investigators will assess the effect of this intervention on frequency of medical errors, evaluate the use and usability of this platform from the perspective of those that interact with it, and use these results to develop a dissemination plan to spread implementation and use of this platform across other similar institutions.

EnCoRe MoMS: Engaging Communities to Reduce Morbidity From Maternal Sepsis (Aim 2)

Sepsis is the second leading cause of maternal death in the U.S. For racial and ethnic minoritized birthing people, especially those who are Black, living in poverty, and from underserved communities, labor and postpartum are particularly vulnerable risk periods. The goal of this multi-center, multidisciplinary observational study is to optimize risk prediction accounting for the social determinants of health, and establish a novel maternal care continuity model to reduce sepsis- related death and disability and increase maternal health equity.

EnCoRe MoMS: Engaging Communities to Reduce Morbidity From Maternal Sepsis (Aim 1)

Sepsis is the second leading cause of maternal death in the U.S. Labor and postpartum are particularly vulnerable risk periods. The goal of this multi-center, multidisciplinary study is to evaluate a maternal sepsis safety bundle.

EnCoRe MoMS: Engaging Communities to Reduce Morbidity From Maternal Sepsis (Aim 3)

Sepsis is the second leading cause of maternal death in the U.S. For racial and ethnic minoritized birthing people, especially those who are Black, living in poverty, and from underserved communities, labor and postpartum are particularly vulnerable risk periods. The goal of this multi-center, multidisciplinary observational study is to establish a novel maternal care continuity model to reduce sepsis- related death and disability and increase maternal health equity.

Head-Only Draping in Pediatric Tonsillectomy

This single-center, interventional study will compare 30-day postoperative infection rates in pediatric tonsillectomy performed with either head-only draping or traditional full-body draping. Secondary analyses will evaluate differences in waste production, material and disposal costs, and provider attitudes between the two draping techniques. This study will randomize participants 1:1 to either the head-only draping cohort (intervention) or the full-body draping cohort (control).