8 Clinical Trials for Various Conditions
The investigators are doing this research study to find out if giving a drug called prasugrel, which is used to prevent blood clots, can reduce reactions to aspirin in people with aspirin exacerbated respiratory disease (AERD), and to learn why taking aspirin every day can work as a treatment for people with AERD. People with AERD have symptoms of asthma, severe runny nose, polyps in the nose, and develop allergic reactions if they take medications like aspirin. People with AERD can be desensitized to aspirin in order to be able to safely use it daily, but the investigators do not know if prasugrel may prevent reactions to aspirin and provide a safer way for people with AERD to tolerate aspirin. The investigators also want to understand what is different about the cells and urine from subjects who have AERD, in comparison to subjects who have asthma but do not have AERD and subjects who have allergic rhinitis but do not have asthma. Lastly, the investigators want to understand how aspirin acts differently in subjects who have AERD, in comparison to subjects who have asthma but do not have AERD.
The overall aim of the study is to determine the clinical efficacy and mechanisms of action of anti-IL-4a (dupilumab) as treatment for patients with Aspirin-Exacerbated Respiratory Disease (AERD).
Aspirin Exacerbated Respiratory Disease (AERD) is a relatively homogeneous disease characterized by adult-onset severe asthma, development of non-cancerous growths in the nasal canal (i.e. nasal polyps) and aspirin allergy. The cause of AERD is unknown, although likely results from environmental insults in combination with genetic susceptibility. AERD disease homogeneity increases the possibility of discovering narrowly-defined genetic contributors, and makes it an ideal population to study the genetic and epigenetic changes that cause asthma. Researchers recently discovered that gene expression of epithelial growth and repair (EGR) genes are substantially decreased in bronchial airway epithelial cells of severe asthmatics compared to less severe asthmatics and healthy controls. This new finding indicates that epithelial integrity and related processes may be of primary importance to the development of severe asthma, and potentially the severe asthma subtype, AERD. This finding was later supported in a subsequent lab model, which showed that blocking a central epithelial repair and differentiation gene, human epidermal growth factor receptor 2 (ERBB2), decreased healing time of bronchial epithelial cells after injury. Thus, the objective of the proposed study is to determine whether EGR gene are also down-regulated in AERD, a homogeneous severe asthma subtype. As an extension, the researchers will also determine whether genetic mutations and/or epigenetic changes relate to and potentially explain this down-regulation of EGR genes. Specifically, the researchers plan to obtain gene expression of freshly brushed nasal airway epithelial cells of 140 AERD patients, 70 non-aspirin sensitive asthma patients, and 35 healthy controls, noting that nasal epithelial gene expression has recently been shown to mirror lung epithelial changes in asthmatic airways. Swabbing the nasal canal for epithelial cells allows to evaluate airway epithelial cell gene expression non-invasively. Our experimental design contrasts AERD gene expression profiles against healthy controls, and determines whether EGR genes are depressed in AERD relative to health controls. As a corollary, the researchers look to discover an AERD-specific gene expression profile which may one-day aid in diagnosis and expand current knowledge of disease mechanisms. As an extension, the researchers will correlate gene expression changes, specifically any finding of down-regulated EGR genes, with methylation changes (i.e. epigenetic changes) and genetic mutations.
The overall aim of the study is to determine the efficacy of oral ifetroban, a novel antagonist of T prostanoid (TP) receptors, as a treatment for patients with aspirin-exacerbated respiratory disease (AERD).
The purpose of this phase 2 study is to assess the safety and efficacy of oral ifetroban for the treatment of aspirin-exacerbated respiratory disease (AERD). AERD is a disease that involves asthma, recurring nasal polyps, and respiratory reactions to aspirin and other nonsteroidal anti-inflammatory drugs.
The primary objective of the study is to determine the safety of oral ifetroban compared to placebo as measured by a \> 20% decrease in FEV1 compared to baseline following a dose of Investigational Medicinal Product (IMP) (Study Day 1 or 2) prior to initiation of the aspirin challenge.
The purpose of this trial is to test the hypothesis that a treatment diet low in omega-6 fatty acids and high in omega-3 fatty acids can cause improvement in asthma symptoms, nasal symptoms, and pulmonary function in patients with aspirin-exacerbated respiratory disease (AERD).
To diagnose aspirin hypersensitivity in asthmatics by using and safe, low-dose aspirin oral challenge. Hypothesis 1: A low dose of oral ASA (20 or 40 mg) will induce significantly different concentrations of arachidonic acid metabolites in ASA-sensitive asthmatics as compared to ASA-tolerant asthmatics. Hypothesis 2: The low dose (20 or 40 mg) ASA challenge will be well tolerated by ASA-sensitive asthmatics.