An Open-label Study to Identify Molecular Markers of Steroid Resistance
Status:
Terminated
Trial end date:
2018-01-09
Target enrollment:
Participant gender:
Summary
Aim 1: To assess steroid sensitivity to mometasone furoate (MF) in cultured nasal polyp
explant tissue in vitro.
Aim 2: To assess steroid sensitivity in vivo in each subject by comparing symptom scores,
nasal endoscopic findings before and following 4 weeks of treatment with mometasone furoate
nasal spray (MFNS) and by comparing tissue immunohistology in NP biopsies pre- and
post-treatment withA MFNS.
Aim 3: To characterize the molecular signature of gene mRNA expression in "steroid-sensitive"
and "steroid-resistant" NP using microarray on NP tissue pre- and post-MFNS treatment.
Hypothesis 1: Genes that regulate apoptosis are dysregulated in nasal polyp (NP) inflammatory
cells, epithelial cells and smooth muscle actin myofibroblasts leading to persistence of
inflammatory cell infiltration and abnormal epithelial and myofibroblast cellular
proliferation. These can be corrected by mometasone. Apoptosis-regulating genes that cannot
be corrected by mometasone are upregulated in steroid-resistant NP.
Elucidation of this dysregulation may prove insightful in understanding the mechanism of
action of mometasone in NP and identifying potential molecular targets that will increase
steroid sensitivity or, conversely, overcome steroid resistance.
Hypothesis 2: There is a molecular signature of gene expression in NP that signifies steroid
sensitive NP (SS-NP). This signature is altered in steroid resistant NP (SR-NP).
Elucidation of differences in the molecular signature of SS-NP versus SR-NP before and after
treatment with mometasone furoate (MFNS) will provide novel insight into treatment of NP with
steroids.
Phase:
Phase 4
Details
Lead Sponsor:
Massachusetts General Hospital
Collaborators:
Massachusetts Eye and Ear Infirmary Merck Sharp & Dohme Corp.