Clinical Research Directory

Biologics in Chronic Rhinosinusitis With Nasal Polyposis

The prevalence of Chronic Sinusitis with Nasal Polyps (CRSwNP) in the United States is estimated at roughly 4%, which equates to over 13 million Americans. Until recently, the only medical treatment options available for patients with CRSwNP were corticosteroids, with surgery reserved for medical failure. The development of biologic medications over the last 5 years has revolutionized the treatment of CRSwNP. Three biologic medications have been FDA approved and available for the treatment of CRSwNP: dupilumab, omalizumab, and mepolizumab. However, data from the clinical trials for these drugs do not show universal improvement across all patients with CRSwNP. In fact, there is a wide range of outcomes for patients in these trials. The result is that clinicians have no way of knowing which specific biologic would be the best option for any given patient, nor do they know whether biomarkers can be used to predict response to biologics. It is hoped that findings from this study will inform whether any one biologic has superior outcomes to another and whether clinicians can identify patients at baseline who are most likely to improve on biologic therapy.

In-clinic Endoscopic Polypectomy for Chronic Sinusitis With Nasal Polyps

Chronic rhinosinusitis, also called chronic sinusitis, is a very common life-long disease affecting over 5% of the Canadian population. Its symptoms, including daily facial pain and headache, an inability to breath through the nose and complete smell loss, regularly impair one's ability to work and to enjoy and participate in daily activities. The annual cost of chronic sinusitis to Canada is estimated at $1.3 billion while the government pays an estimated $860 million yearly for chronic sinusitis treatment. Chronic sinusitis with polyps, the most common type of chronic sinusitis, is usually treated with a combination of medications and surgery. Until now, surgical treatment has only been performed in the operating room, at a cost of about $3500 per procedure. But, recent studies have shown that a new procedure, "in-clinic polyp removal", can provide an improvement in patient symptoms to levels equal to those for sinus surgery performed in a hospital operating room. Moreover, in clinic polyp removal has additional advantages including a shorter procedure recovery time, a significantly lower cost to the health care system (about one-tenth the cost or $450), and a shorter wait time for treatment. With the proposed pragmatic trial, the investigators will determine whether the in clinic polyp removal procedure is as good as sinus surgery in the operating room at controlling patient symptoms of chronic sinusitis. The investigators will also determine the cost and health-benefits for a patient, the healthcare system and for society of in clinic polyp removal in comparison to sinus surgery done in a hospital operating room. The investigators will then know if this new treatment, in clinic polyp removal, can replace sinus surgery as the standard of care for these patients.

Pilot Study of The EPIC Trial

Chronic sinusitis is one of the most common chronic diseases in North America, with over 5% of the Canadian population affected by the disease. Until now, treatment with surgery has been performed only in the operating room. Recently a smaller surgical procedure that is done in the clinic for some patients with chronic sinusitis with polyps has been found to result in symptom control that appears to be similar to that which occurs with sinus surgery. Performing the smaller clinical procedure has advantages including a shorter recovery time for the patient, a much lower cost to the health care system for the procedure, and a shorter patient wait time for the procedure to be done in comparison to sinus surgery performed in the operating room. To know with greater certainty that the procedure performed in the clinic is as good as the operating room sinus surgery, a large multiple investigator randomised clinical trial has been designed. However, before carrying out that trial, a practice run or internal pilot study of that trial is required to ensure that the trial can recruit patients at the rate that is anticipated and that the procedures to obtain the measurements being used for the larger study are adequate.

Complete Remission After Treatment With Biologics for Nasal Polyps

In this RCT the investigators randomize patients who are treated with biologic treatment (Nucala or Dupixent) due to nasal polyps and have controlled disease within the last year to either stop treatment og continue as a control group.

A Study to Evaluate 611 in Patients With Chronic Rhinosinusitis With Nasal Polyps

This study will evaluate the effect and safety of 611 in patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)

Effect of Full-House ESS With Nasopharyngeal Lymphoid Tissue Ablation on Nasal Polyps

This study is designed to evaluate whether the addition of nasopharyngeal lymphoid tissue ablation to full-house endoscopic sinus surgery (ESS) provides superior control of nasal mucosa inflammation compared to full-house ESS alone in patients with nasal polyps. Thirty-two adult participants will be randomly assigned to undergo either full-house ESS only or full-house ESS combined with nasopharyngeal lymphoid tissue ablation. The primary outcome will be assessed through changes in inflammatory cell profiles at 1, 3, and 6 months postoperatively. Secondary outcomes include inflammatory cytokine levels, symptom scores, endoscopic findings, polyp recurrence rates, and safety measures.

Mechanisms of Benefit of IL4RA Inhibition in Aspirin-Exacerbated Respiratory Disease

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 Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) and Aspirin-Exacerbated Respiratory Disease (AERD).

Moving Towards Precision Medicine in United Airways Disease: Unraveling Inflammatory Patterns in Asthmatic Patients With or Without Nasal Polyps

Asthma and chronic rhinosinusitis (CRS) are inflammatory diseases of the respiratory tract, asthma from the lower part, and CRS, from the upper part. In theory, these parts are correlated as if they are one single organ, namely "united airways", which means that if one is affected by any condition, the other might be impacted as well. However, this relationship has not yet been described down to the cellular and molecular levels. By investigating patients that have (1) asthma and CRS with nasal polyp, (2) asthma and CRS without nasal polyp, and (3) just CRS with nasal polyp, we aim to determine the correlation of the upper and lower part of the respiratory tract. At first, the characterization of disease will be determined by established clinical criteria, such as lung function, blood analysis for the presence of eosinophils (a type of white cells), and nasal polyp score. To continue, in-depth analysis of nose, oropharynx, and lung samples will help gain information about the inflammatory profile and local microbiome of the three different groups of patients through molecular and cellular assays. The results of this study will help to describe the hypothesis of the united airways which will provide better guidance for medical treatment of asthma and CRS with or without polyp, thus improving the life quality of patients.

Interleukin-4Ra Blockade by Dupilumab Decreases Staphylococcus Colonization and Increases Microbial Diversity in CRSwNP

Hypothesis: The investigators hypothesize that in patients with CRSwNP who demonstrate sinus colonization with staphylococcus aureus, the administration of dupilumab will be associated with decreased staph colonization and an increase in microbial diversity. Primary Objective will be to demonstrate that dupilumab reduces staphylococcus aureus (phyla firmicutes) abundance while increasing microbial diversity in patients with CRSwNPs who are culture positive for staph aureus at enrollment. Secondary Objectives will be to correlate reduction in Staph aureus abundance and improved bacterial diversity with increased expression of anti-microbial proteins (ß-defensins1-4) and cathelicidin LL-37. In addition, the investigators will correlate improvements in microbial diversity/decreased staph abundance with clinical improvements as assessed via questionnaires and objective/subjective smell function and also as improvements in cellular/immune T2 inflammation as assessed by reduced expression of T2 cytokines/chemokines and eosinophil/eosinophil-derived proteins.

Dupixent Study for Alternate Administration

Investigators will investigate an alternate Dupilumab administration schedule in patients with recurrent chronic rhinosinusitis with nasal polyposis, who have a history of full endoscopic sinus surgery and are on appropriate topical medical therapies. Specifically, investigators will investigate if the alternate schedule of drug administration is non-inferior in both subjective and objective outcomes.

Does Batten Grafting Improve Nasal Outcomes in Septoplasty and Turbinate Reduction?

The objective of this study is to compare the effectiveness of batten grafts plus septoplasty and turbinate reduction (intervention arm) compared to septoplasty and turbinate reduction alone (control arm), both in terms of subjective and objective assessments.

BIOlogics in Severe Nasal POlyposis SurvEy.: a French Registry

With a prevalence of 2-4% in western countries, Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is of major concern regarding its substantial impact on the social and physical quality of life. So far, endoscopic sinus surgery remains the treatment of choice when the first line of medical treatment with corticosteroid has failed. During the last 15 years, several studies have shown that CRSwNP is associated with a T helper 2 (T2) immune response leading to B cell release of IgE, mucosal recruitment of eosinophils from bone marrow via Interleukin (IL)-5, IL-4 and IL-13 mediated chemoattractant production. New biologic agents capable of blocking T2 cytokines have been developed in the field of eosinophil-associated diseases, shifting the paradigm of treatment for patients with CRSwNP. In the near future, endotype profiling with accurate biomarkers will be mandatory to tailor the treatment of nasal polyposis with specific biologic therapies. Herein the investigators propose a prospective study monitoring medical records of CRSwNP patients who undergo biologic treatments. The objectives are to assess treatment efficacy on quality of life, to report clinical and biological criteria for prescription and to measure tolerance and compliance.Patient-reported outcomes will be addressed according to their initial clinical profile (allergy, asthma, NSAID, gastroesophageal reflux disease, obstructive apnea, otologic disorder, smoke habit).