29 Clinical Trials for Various Conditions
This is a multi-dose study with RCT1100 and is designed to provide safety, tolerability and preliminary efficacy data for future clinical studies.
A Study to Assess the Effect of the HFO MDI Propellant on Mucociliary Clearance Compared to the HFA MDI Propellant in Healthy Participants
This study will provide important mechanistic information regarding the effect of inhaled mannitol (Bronchitol) in people with cystic fibrosis (PwCF) with moderate to severe disease who are already using elexacaftor/tezacaftor/ivacaftor (E/T/I). Many patients have already discontinued hypertonic saline and other pulmonary therapies because of the profound effect of E/T/I of their symptoms and lung function. Further, because both inhaled osmotic agents (i.e., Bronchitol, hypertonic saline \[HS\]) and E/T/I are believed to exert their beneficial effects through improvements in mucociliary clearance (MCC), it is unknown if the combination of these therapies might be additive or are redundant in a population with moderate to severe disease where bronchiectasis and chronic infection persists, and where eventual decline in lung function is expected over time. This study, therefore, will be the first to determine whether "add on" therapy with inhaled mannitol is able to further accelerate MCC in E/T/I patients. These data would provide some guidance regarding the use of these approved therapies in PwCF.
Single center, randomized, placebo- controlled study to assess change in mucociliary clearance of moderate to severe asthma patients after treatment with dupilumab or placebo.
This purpose of this study is to determine whether nasal delivery of heated and humidified air for a period of 4 hours will improve the clearance of mucus from the lungs of patients with chronic obstructive pulmonary disease (COPD). Mucus clearance will be measured using a nuclear medicine imaging procedure called a mucociliary clearance scan. Humidified air (with added oxygen if needed) will be delivered from the Fisher and Paykel myAirvo2 heater/humidifier through an Optiflow nasal cannula.
This study intends to evaluate the nasal mucociliary clearance (NMC) by determining the value obtained for saccharin transit time (STT) test over the course of 12 hours following a single cigarette use in adult smokers, to compare it relative to never smokers, and to examine the relationship between plasma nicotine levels and STT value in smokers and never smokers. Safety will also be monitored during the study. The planned maximum study duration for a single study participant from Screening through completion of study will be 33 days.
This study will assess the effect of inhaled AZD5634 on Mucociliary clearance (MCC) in patients with Cystic fibrosis (CF) after single-dose administration.
This is a randomized, double-blind, cross-over, vehicle-controlled study to determine whether GS-5737 in 2.8% saline accelerates mucociliary clearance (MCC) in healthy subjects, compared to vehicle of 2.8% saline alone.
The purpose of this research study is to examine the effects of two weeks of daily dosing of inhaled salt water mist (hypertonic saline - HS) on actual measurements of mucociliary and cough clearance in patients with the chronic bronchitis type of Chronic Obstructive Pulmonary Disease (COPD. Defective mucociliary clearance (MCC) is central to the development and/or worsening of several kinds of lung diseases, including COPD/chronic bronchitis (CB), cystic fibrosis (CF), and bronchiectasis. In each case, defective MCC leads to the development of lung infections and damage to the airways from ongoing inflammation caused by a person's inability to clear mucus from the lungs. The investigators' previous studies have shown that the administration of inhaled HS (hypertonic saline) not only acutely accelerates MCC in CF, but also that repetitive use "resets" the baseline rate of MCC within 2 weeks. It is likely that the sustained effect of HS on MCC was responsible for the \~60% reduction in the frequency of pulmonary disease exacerbations, reduced antibiotic use and improved lung function in a long-term study of HS in CF volunteers. As a result, HS has now become a standard therapy for CF lung disease and its success raises optimism that similar benefits might occur in patients with CB. In this study the investigators will use mildly radioactive particles, technetium bound to sulfur colloid, to measure and compare the sustained effects on mucus clearance of two weeks of daily dosing of 7% hypertonic saline versus a low salt control treatment for subjects with CB. We will also be collecting sputum and breath condensation to analyze for protein and inflammatory changes that might occur with exacerbations. Our long term goals are to improve our understanding of MCC in health and disease and to develop better therapies that support and/or restore MCC in patients with these diseases to reduce lung infections.
The purpose of this research study is to learn about how long hypertonic saline (HS) works in healthy subjects. Inhaled hypertonic saline is one of the medications used to treat Cystic Fibrosis (CF). In CF and more common lung diseases like chronic bronchitis, mucus builds up in the lungs. Hypertonic saline and other medications currently being developed may help patients with these lung diseases by speeding up mucus clearance from the lung. For these treatments to be effective, they likely need to be able to act for at lease several hours. Investigators are able to measure how lung treatments like hypertonic saline work by conducting a Mucociliary Clearance (MCC) scan. Currently, the investigators do not know how long hypertonic saline works in people who do not have CF. Investigators plan to use this information to improve the design and testing of new treatments for patients with chronic bronchitis. Objectives: 1. The investigators will use MCC measurements to determine the durability of action of hypertonic saline in healthy (i.e. non-CF) subjects. 2. The investigators will determine the intra- and inter-individual variability of baseline MCC measurements using a slow inhalation/large particle protocol in healthy subjects to guide future sample size calculations.
Direct measurement of mucociliary and cough clearance (MCC/CC) has been used as a biomarker in cystic fibrosis (CF). Additional knowledge of the performance of this biomarker is needed to inform exploratory clinical trial design in support of programs to develop new inhaled therapies for CF. We hypothesize that MCC/CC measurements can be used to determine the durability of action of agents like hypertonic saline (HS) which increase epithelial lining fluid height.
The investigators are looking at the effects of baby shampoo nasal irrigation on the movement of mucous in the nose in patients who have undergone sinus surgery for chronic sinus problems.
The purpose of this Phase 1 research study is to identify a dose of inhaled endotoxin that is safe (does not cause prolonged cough, shortness of breath or other problems), but causes changes in sputum cell samples that the scientists can measure. The investigators are also interested in seeing if the exposure to the endotoxin decreases the body's natural ability to clear mucus from the lungs.
Healthy volunteers and patients with diseases that involve problems clearing mucus from the lungs will be examined and tested to better understand the reasons for recurring lung infections in these patients and to try to develop better ways to diagnose and treat them. The study will also try to identify the genes responsible for these diseases. Healthy volunteers 18 years of age and older and patients 2 years of age or older with suspected primary ciliary dyskinesia (PCD), variant cystic fibrosis (CF) or pseudohypoaldosteronism (PHA) may be eligible for this study. Patients enrolled in the Natural History Study of Nontuberculous Mycobacteria at NIH or other NIH natural history protocols may also be enrolled. Participants undergo the following tests and procedures during a 1-day visit at the NIH Clinical Center, as follows: All patients and normal volunteers have the following procedures: * Physical examination and review of medical and genetic history and family genetic history. * Lung function test and measurement of oxygen saturation level. * Nitric oxide measurement to measure the amount of nitric oxide production in the nose: A small tube is placed in the nose while the subject breathes through the mouth into a cardboard tube. All patients have the following additional procedures: * Blood tests for liver and kidney function, blood count, immunoglobulins and pregnancy test (where appropriate). * Blood test or buccal scrape (brushing the inside of the cheek) to obtain DNA to look for gene mutations that cause PCD, CF or PHA. * Scrape biopsy of cell lining the inside of the nose: A small toothpick-sized plastic stick with a tiny cup on the end is used to get nasal lining cells to look at the cilia (hair-like structures that move mucus). * Semen analysis (in some men) to test sperm tail function or structure. Patients suspected of having a variant of CF or PHA, including nontuberculous mycobacterial lung disease, have the following additional procedures: * Sweat chloride test: A medicine is placed on the arm to produce sweat; then, a very low level of electric current is applied for 5 to 12 minutes. Sweat is collected in a plastic tube and tested for salt content. * Blood draw for CF genetic testing, if necessary, and to measure levels of the enzyme trypsin. * Saliva collection to measure sodium and chloride content. * Nasal potential difference to measure the electrical activity of the cells lining the inside of the nose: A soft plastic tube filled with a salt solution is passed into the nasal passage and a sterile needle is placed under the skin of the arm. This test provides information about how the lining of the nose is able to get used to changes in temperature and humidity. (Normal volunteers also have this test.)
The purpose of this study is to determine whether lung mucociliary clearance (MCC) can be significantly enhanced in healthy subjects by one week of inhalation of nebulized levalbuterol aerosol, as compared to racemic albuterol or placebo. Subjects will inhale one week of levalbuterol, one week of racemic albuterol, and one week of placebo, in a randomized order.
The objective of this study is to determine the effect of airway surface liquid (ASL) volume on mucociliary clearance in cystic fibrosis (CF). A two-isotope nuclear medicine technique will be utilized. This pilot trial will include the imaging of n=7 CF subjects and n=7 healthy subjects. The trial will include one study visit per subject that will take approximately 3 hours. Hypothesis: The simultaneous imaging of both a "floating" and a "penetrating" radioisotope tag will allow the relative effect of airway surface liquid volume on mucociliary clearance to be determined when evaluated in CF and normal subjects.
The purpose of this research study is to test the ability of Mucinex, an oral, over-the-counter, FDA approved expectorant) to stimulate the clearance of inhaled particles from the subject's lungs (called "mucociliary clearance"). The study will also monitor the metabolism of the drug by the subject's body.
Cystic Fibrosis (CF) is an autosomal recessive disease cause by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) manifesting in multiple organs, the most common cause of morbidity and mortality continues to be the pulmonary manifestation. CFTR dysfunction leads to reduced mucociliary clearance, impaired innate immune system function in the lungs (within the airway surface liquid \[ASL\] lining the epithelial barrier of the lungs) and reduced ASL hydration (stickier mucus). To try and help correct this underlying defect patients have been performing airway clearance for decades using different techniques (Percussion and postural drainage \[P\&PD\], Positive expiratory pressure \[PEP\], Oscillatory positive expiratory pressure \[OPEP\], High-frequency chest compression \[HFCC\], exercise), inhaled mucolytics (Hypertonic Saline, Pulmozyme) and inhaled antibiotics. However, performing daily airway clearance can be a large burden on patients and their families with a median number of daily therapies around 7 and average time spent on therapies at almost 2 hours daily. This high treatment burden leads many patients to have reduced adherence to their regimens and multiple studies have shown around 20% of patients performing no daily airway clearance. Since the release of highly effective CFTR modulator therapy patients have experienced improvements in lung function measurements and imaging-based ventilation measurements, reduction in pulmonary exacerbations, and improvement in daily symptom scores. Over 80% of patients and their families and over 95% of clinicians in the United States support the idea of trials looking into the simplification of airway clearance regimens. Combining the inability of most patients to complete their daily regimens, patient and clinician interest in treatment simplification research, and the overwhelming cost of most inhaled medications in cystic fibrosis with the improvement in mucociliary transport and symptoms with highly effective modulator therapy suggests a research program aimed at reducing the treatment burden of daily airway clearance should be considered. The investigators propose the following: determine if there is additional benefit in continuous airway clearance regimens after starting Elexacaftor-Tezacaftor-Ivacaftor (ETI) and if so, is this benefit noticeable on pulmonary function testing and imaging.
This is a pilot study investigating the effectiveness and clinical efficacy of airway clearance therapy (ACT) in cystic fibrosis (CF). Enrolled subjects will undergo measurements of mucociliary clearance (MCC) and exhaled biomarkers at baseline and after 3 different forms of ACT: high frequency chest wall oscillatory vest, oscillatory positive expiratory pressure device, and whole-body vibration.
The purpose of this single arm clinical trial is to evaluate the effects of 7% hypertonic saline (HS) delivered by nebulizer on clearance of mucus from the lungs in people with bronchiectasis (dilated airways) not due to cystic fibrosis. Mucociliary clearance (MCC) to measure the rate at which a person's lungs can clear inhaled particles will be assessed at baseline, and after acute (single dose) HS treatment, as well as after two weeks of treatment with HS. The study has two main questions: 1. Evaluate the repeatability MCC measures in people with non-CF bronchiectasis 2. Compare MCC at baseline (before treatment with HS), after a single dose of HS (acute effect of HS), and after two weeks of treatment with HS twice a day (sustained effect of HS). Participants will participate in up to 5 study visits if completing both Aim 1 and Aim 2: 1 screening/enrollment visit, 2 baseline visits (1 baseline visit if only participating in Aim 2), 1 visit during which first dose of HS would be administered and assessed, and 1 visit after 2 weeks of treatment with HS.
The purpose of this study is to measure mucociliary clearance (MCC) in groups of subjects with the disease Primary Ciliary Dyskinesia (PCD) caused by mutations in different genes, and compare to healthy subjects. Some of these genes are associated with a milder clinical phenotype. This study seeks to determine if the milder phenotype is a result of mutations in a set of specific genes. The hypothesis is that subjects with PCD caused by mutations in the milder group will maintain a low, but significant rate of mucociliary clearance, while patients with mutations in genes in the more severe group will have a complete absence of mucociliary clearance. These studies will help inform future treatment strategies.
When developing new medications for lung diseases like Cystic Fibrosis (CF), scientists perform lab experiments using cells from the airways, physiology studies of how the lungs change when a drug is given, and clinical studies to determine how drugs affect overall health. The investigators of this study are seeking to develop computer models that will predict how patients will respond to drugs by just doing lab studies on cell samples from their noses. Such models would allow for medications to be developed more rapidly for all patients and allow treatments to be personalized as well. In order to develop these computer models a series of tests will be performed on patients who have CF. Tests will include sampling cells from the nose and measuring lung physiology using a combination of different imaging, breathing, and other studies performed both before and after participants take a therapy. Similar tests will be performed on people who do not have CF, and on the parents of the CF participants who carry a single CF gene because this will provide information on how specific genes might affect CF lung disease.
The investigators are developing a new nuclear medicine imaging technique for measuring liquid absorption in the airways that can be applied to screen new medications being developed to treat cystic fibrosis (CF). The investigators believe that the absorption of the small molecule radiopharmaceutical Indium 111 diethylene triamine pentaacetic acid (In-DTPA) will indicate changes in liquid absorption in the airways and demonstrate whether new CF medications will be effective. In this study the investigators will determine whether the imaging technique will demonstrate similar results when it is repeated on different days. They will also determine how their results change when subjects utilize several common CF medications.
The investigators are developing a new nuclear medicine imaging technique for measuring liquid absorption in the airways that can be applied to screen new medications being developed to treat cystic fibrosis (CF). The investigators believe that the absorption of the small molecule radiopharmaceutical Indium 111-diethylenetriaminepentaacetic acid (In-DTPA) will indicate changes in liquid absorption in the airways and demonstrate whether new CF medications will be effective. In this study the investigators will further develop this technique through testing involving pediatric CF patients and healthy control subjects.
Previous work demonstrated that inhaled hypertonic saline (HS) reduces exacerbation frequency and improves lung function in adults with cystic fibrosis (CF). It is unclear, however, whether HS will benefit young patients suffering from CF. The investigators propose to further support the concept that HS can benefit children with mild CF lung disease by performing a relatively short, placebo controlled study of HS in 5-12 year olds, using lung function and mucociliary clearance as key outcome measures.
The overall short-term goals of this project include the following: 1) identify the genes that are key to the function of respiratory cilia to protect the normal lung; and 2) the effects of genetic mutations that adversely affect ciliary function and cause primary ciliary dyskinesia (PCD), which results in life-shortening lung disease. The long-term goal of this project is to develop better understanding of the underlying genetic variability that adversely modifies ciliary function, and predisposes to common airway diseases, such as asthma and chronic obstructive pulmonary disease.
The research plan proposes translational studies in relevant animal models and human subjects in order to identify host (genetic) susceptibility factors that confer vulnerability to the prototypal air pollutant, ozone. The results will have significant impact upon, and aid in, understanding mechanisms regulating pro-oxidant lung injury, production and secretion of airway mucins, and clearance of respiratory mucus, and adverse health effects, that occur during and following exposure to airborne respiratory irritants.
The objective of this overall project is to develop a new aerosol-based technique for quantifying liquid absorption in the airways of subjects with cystic fibrosis(CF) that can be used to help develop new therapies. In CF, mutations in the CF gene result in dysfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) ion channel on the cells that line the airway epithelium, causing improper fluxes of ions such as sodium, chloride, and bicarbonate. The so called "low volume" hypothesis of CF pathogenesis contends that abnormal absorption of ions from the airways causes excessive absorption of liquid, resulting in an airway surface liquid layer that is dehydrated and difficult to clear. Here we are measuring the absorption rate of a radiolabeled small molecule (DTPA) from the lungs of cystic fibrosis patients and healthy controls. We hypothesize that the molecule will absorb more quickly in cystic fibrosis patients. Further studies will be performed to determine if DTPA absorption is related to liquid absorption in the airways.
The purpose of this research study is to explore the mechanism of action of Mucinex, an oral, over-the-counter, FDA approved expectorant in patients with acute respiratory tract infections.