Clinical Research Directory

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 Comparison of Static and Dynamic PET/CT (HYPOTHESIS Generation Study)

The general purpose of this initial study is to evaluate whether parametric PET/CT improves diagnosis and treatment monitoring in select diseases. The specific aim of the HYPOTHESIS GENERATION study is: 1\. To obtain and compare parametric as well as traditional static PET/CT images and determine the number of lesions identified on each type of scan.

Supporting Weak Immune System During Autoimmune Therapy: Testing Panzyga to Prevent Infections

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Panzyga for Prevention of Major Infection in Patients with Hypogammaglobulinemia and Autoimmune or Rheumatic Conditions Receiving Treatment with B-cell Depletion Therapy

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.

Rhu-pGSN for Acute Respiratory Distress Syndrome (ARDS)

BTI-203 is a randomized, double-blind, placebo-controlled, multicenter, Phase 2 proof-of-concept (POC) study to evaluate the efficacy and safety of rhu-pGSN plus standard of care (SOC) in subjects with moderate-to-severe ARDS (P/F ratio ≤150) due to pneumonia or other infections. Potential subjects hospitalized with pneumonia or other infections are to be screened within 24 hours of diagnosis of ARDS.

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. ...

Immune Biomarkers for Predicting Complications After Liver Transplantation

This multicenter prospective observational study will evaluate immune biomarkers in adults undergoing liver transplantation. The study aims to describe how immune markers change before and after transplantation and to assess whether these changes are associated with complications such as infections, acute cellular rejection, and viral reactivation during the first year after transplantation. Blood samples will be collected before transplantation, on days 0, 3, and 7 after transplantation, and at months 1, 3, 6, and 12. Biomarkers evaluated will include cytokines, interferons, immunoglobulins, lymphocyte populations, monocyte HLA-DR, neutrophil CD64, functional immune assays, checkpoint molecules, and Torque Teno Virus. Clinical outcomes will be recorded prospectively. Biomarker results will be used for research purposes only and will not modify immunosuppressive treatment or other clinical decisions.

Comparing the Diagnostic Sensitivity and Specificity of Pleural Fluid N-Terminal Pro B-type Natriuretic Peptide (NT-proBNP) and Other Biochemical Gradient Criteria in Distinguishing Heart Failure and Non-heart Failure Related Pleural Effusions (CENTRE Study)

To assess the discriminative properties of pleural fluid (PF) N-terminal-proB-type-natriuretic-peptide (NTproBNP) levels in identifying heart failure (HF)-associated pleural effusions (PE).

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.

TriVerity™ for Improved Management of Emergency Department (ED) Patients With Suspected Infections

A pre/post interventional use trial, with ED patients who are initially triaged to locations other than a dedicated patient room in the main ED (e.g., waiting room, hallway bed, and/or the staging area/fast track area) with suspected infection and tachycardia or fever will be enrolled. Study conduct will be performed under an Investigational Device Exemption (IDE) from the Food and Drug Administration (FDA). Participants in the pre-phase, treated with standard of care, will be gathered from a retrospective database using propensity matching, whereas participants in the post-phase will be managed incorporating the TriVerity™ Acute Infection and Sepsis Test results with standardized guidance for interpretation and resulting management actions. Many outcomes will be captured and compared between the pre- and post-phase phases including sepsis bundle compliance, patient disposition, appropriate use of antimicrobials (antibiotics and antivirals) and health economic findings. Safety measures for participants in the post-phase will include patient follow-up at predefined time points. The objective is to demonstrate improvement of patient management when incorporating the TriVerity Test result compared to standard of care. Improvements based on diagnostic (bacterial vs viral vs non-infectious inflammation) and prognostic (need for 7-day ICU level care) readouts of the TriVerity Test result will be tracked.

Pharmacokinetics of Ertapenem in Patients Aged Over 75

In geriatric departments, physicians are faced with two difficulties, first the increasing number of infections caused by multiresistant bacteria, especially extended spectrum β-lactamase (ESBL) producing enterobacteria strains and second, the poor venous access frequently encountered in elderly population. Giving antibiotics subcutaneously would be an interesting alternative, all the more as intramuscular injection is contraindicated in case the of anticoagulant therapy. Unfortunately, few data are available about subcutaneous (SC) administration. Ertapenem is a recent long-acting parenteral carbapenem indicated especially in the treatment of ESBL infection. Its subcutaneously administration has been tested in several studies in Intensive Care Units (ICU) and internal medicine wards with promising results regarding clinical and pharmacokinetics data. An alternative to the IV Ertapenem administration is needed because of poor venous access and behavioural abnormalities commonly present in infected elderly population. Ertapenem is currently SC administrated in geriatric departments if no other option is available. Moreover elderly patients often present several comorbdities, polymedication, renal insufficiency, cachexia which may disturb antibiotics pharmacokinetics. The aim of the study is to obtain pharmacokinetic data of SC and IV Ertapenem administration in elderly population, obtain PK/PD parameters adapted to time-dependent antibiotics (T%\>MIC) and descriptive data of occurrence of adverse effects and evolution of signs of infection.

Study to Evaluate Immunogenicity, Safety and Tolerability of Adjuvanted and Non-Adjuvanted H2N3 Influenza Vaccines in Adults

This Phase 1, randomized, observer-blind, dose-ranging clinical study is evaluating 6 different formulations of MF59-adjuvanted and non-adjuvanted H2N3 influenza vaccine. Approximately 600 healthy adult subjects are to be randomized into 1 of 6 possible treatment groups with 100 subjects per group, stratified by age group (born after or before 1968). Each subject will receive an influenza vaccine injection on Day 1 and Day 22. Subjects will be followed up for approximately 12 months after the second vaccine injection. The primary immunogenicity analysis is based on the Day 1, Day 8, Day 22, Day 29, and Day 43 serology data. The primary safety analysis is based on solicited local and systemic adverse events (AEs) reported within 10 days after each vaccination, unsolicited AEs reported within 3 weeks after each vaccination, and serious AEs (SAEs), medically attended AEs (MAAEs), AEs leading to withdrawal from the study, and AEs of special interest (AESIs) reported throughout the study.

Exactech Shoulder Post Market Clinical Follow-up Study

The objective of this study is to collect and evaluate long-term clinical and radiographic outcomes data in order to better understand the safety and performance of the shoulder arthroplasty over time. This study will follow subjects long-term for a minimum of 10-years, without an early-term restriction on the amount of time they will be followed.

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.

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.

Infectious Complications After Esophagectomy

Infectious complications represent the most common postoperative adverse events following esophagectomy for cancer, such as pneumonia (15% of cases). These complications increase immediate risks, lengthen hospital stays, and worsen patient quality of life. The population includes patients admitted to intensive care after esophagectomy for cancer between January 1, 2017, and December 31, 2024. The study focuses on this population due to the increasing incidence of esophageal cancer, the increased use of surgery for these indications, and the importance of postoperative infections in these complex procedures, despite their understudied nature in the current literature. Identifying modifiable risk factors could lead to corrective measures and thus improve the prognosis of postoperative patients. The research focuses primarily on the incidence, types, factors, and prognosis associated with the occurrence of infections after esophagectomy for cancer. It also includes an analysis of the pathogens involved, their resistance profiles, and the antibiotic therapies used in first-line probabilistic treatment.

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.

Human Neutrophil Lipocalin as an Aid in the Diagnosis of Bacterial Infection in the Emergency Department

The aim of this study is to improve the medical care of patients with infections for which the cause cannot be clearly identified as bacterial or viral. To achieve this, we are investigating a new inflammatory marker in the blood that may help identify severe bacterial infections more quickly. Early detection is important to prevent complications and ensure that patients receive the most appropriate treatment as soon as possible. This is an observational study. The knowledge gained from this study may help improve the care of patients with infections of unclear origin by supporting faster diagnosis, earlier treatment, improved risk assessment, and better planning of follow-up care.

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.

Effect of Synapse Medicine Decision Support on Inpatient Pharmacist Efficacy and Efficiency

Adverse drug events (ADE) are common and dangerous in the hospital and following discharge to the ambulatory setting. One cause of ADEs in both settings is medication regimen inappropriateness, including polypharmacy, drug-drug interactions, and medications that are inappropriate or inappropriately dosed given patients' age, renal, and hepatic function. Hospitalization provides a good opportunity to investigate medication appropriateness given new or worsening conditions and available expertise. Inpatient pharmacists are medication experts and often round with medical teams, but they may not always have all the information available at their fingertips to make optimal recommendations regarding medication appropriateness for each patient. Clinical decision support to pharmacists at the point of care has potential to improve the speed, quantity, and quality of medication recommendations to inpatient teams; any subsequent improvements to medication regimen appropriateness have the potential to reduce ADEs in the hospital and after discharge. Specific Aims and Objectives Aim 1: Implement real-time decision support regarding medication regimen appropriateness among pharmacists who round with inpatient medical teams. Aim 2: Determine the effects of this intervention on the number of medication regimen recommendations and time spent per recommendation Aim 3: Evaluate the use and usability of the decision support tool and develop strategies to mitigate barriers and promote facilitators of implementation using mixed methods implementation science approaches.

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.

Remote Sputum Collection in Cystic Fibrosis

Elexacaftor/Tezacaftor/Ivacaftor or Trikafta improves lung health in people with cystic fibrosis (CF), including decreased cough and mucous production. Diagnosing lung infections has become more challenging due to the decrease in sputum and rise of telehealth services. While the option of collecting sputum samples at home and sending them by mail may be feasible, uncertainty remains about how the collection of samples outside of clinic and delays in testing while in the mail impact infection detection. This study will compare bacterial cultures using sputum samples collected at home versus samples collected in clinic (saline-induced sputum and throat swab). This study seeks to shed light on how valuable home collected samples can be and help us better understand the usefulness of home-collected sputum samples for both clinical and research purposes.

Large Algorithm Setting and Validation Study

In this pilot study, prospectively acquired clinician-collected and participant-collected vaginal swab specimens will be obtained from up to 1000 individuals with signs and symptoms of vaginitis to develop and validate a bacterial vaginosis diagnostic algorithm and evaluate the performance of the Nanopath assay. The Nanopath assay is an amplification-free molecular test that detects pathogens associated with vaginitis. The performance of the Nanopath assay will be assessed by comparing Nanopath assay results to previously FDA-cleared commercial tests and yeast culture.