Interleukin-4Ra Blockade by Dupilumab Decreases Staphylococcus Colonization and Increases Microbial Diversity in CRSwNP
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-65
SponsorUniversity of Virginia
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
History of CRSwNP including subjects with AERD
Sinonasal culture demonstrating staph aureus at visit 1
History of FESS with patent sinus ostia sufficient to obtain culture and tissue samples from the middle meatus
Asthma, if present, should be well controlled
Disqualifiers
Concurrent serious medical problem
Uncontrolled asthma (ACT <20 at screening visit)
Recent (within 60 days) use of oral corticosteroids
Recent (within 60 days) urgent care, ED visit, or hospitalization for asthma
Trial design
Design model
Single group
Treatments tested in this trial
Dupilumab Prefilled Syringe
DrugDupilumab 300 mg
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: Dupilumab treatmentExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
To demonstrate that dupilumab reduces staphylococcus aureus
To demonstrate that dupilumab reduces staphylococcus aureus (phyla firmicutes) abundance. The abundance of Staph aureus will be determined using qPCR of the femA gene and compared at baseline and after 16 weeks of dupilumab treatment. Statistical differences in the quantity of staph aureus (as ascertained by qPCR) will be determined utilizing data obtained from all subjects comparing data obtained at the end of the study in comparison to the beginning of the study.
Time frame
16 weeksSecondary outcomes
1
To correlate reduction in Staph aureus with improvements in clinical status
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. These parameters will be determined using quantitative PCR. In addition, we 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. These will be determined using proximity extension assays (for cytokines/chemokines) and enzyme immunoassays for eosinophil products. Statistical significance of data obtained at end of study will be determined in comparison to baseline samples.
Time frame
16 weeks2
To demonstrate that dupilumab increases microbial diversity
To demonstrate that increases microbial diversity in CRSwNPs who are culture positive for staph aureus at enrollment. Microbial ß-diversity will be quantified via the Shannon Index and compared between baseline and 16-week samples. Microbial diversity (as ascertained by Shannon diversity) will be determined utilizing data obtained from all subjects comparing data obtained at the end of the study in comparison to the beginning of the study.
Time frame
16 weeksSponsors and contacts
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University of Virginia
Lead sponsor
Regeneron Pharmaceuticals
Collaborator
Source ClinicalTrials.gov