An Open-label Study to Identify Molecular Markers of Steroid Resistance
Condition: Nasal Polyps
MeSH terms: Nasal Polyps
Intervention: mometasone furoate
Intervention description: 2 sprays/nostril BID
Intervention MeSH terms: Mometasone Furoate
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 21 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Nasal polyps

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.
    

Eligibility criteria:

        Inclusion Criteria:

        - The subject must fulfill all of the following conditions or characteristics to be
        considered for enrollment:

          1. Male or female between ages 21 - 70 years residing in the Boston area

          2. History of chronic rhinosinusitis (symptoms for at least 3 months). Subject must have
             two or more of the following:

               -  Facial pain/pressure or headache

               -  Nasal congestion

               -  Anterior or posterior nasal drainage

               -  Hyposmia/anosmia

          3. Abnormal CT scan in at least 2 sinuses areas within 3 months

          4. Evidence of bilateral polyps or polypoid mucosa (on nasal endoscopy) with minimum
             polyp/polypoid score of 4 (see scoring system below).

             Exclusion Criteria:

               -  4. History of suggestive of immunodeficiency (i.e. those who have had > one
                  pneumonia in the past 12 months or those with known immune deficiency).

          5. History of cystic fibrosis, Kartagener's syndrome, immotile cilia syndrome,
             hypogammaglobulinemia or bleeding disorder

          6. URI within six weeks prior to enrollment

          7. Intranasal cocaine use

          8. Pregnancy (if applicable

          9. History of fainting

             MEDICATION EXCLUSIONS prior to NP biopsies:

         10. Use of prescription blood thinners

         11. Use of systemic glucocorticoids for two weeks prior to enrollment

         12. Use of intranasal corticosteroids and anticholinergics for three days prior to
             enrollment

         13. Use of an antibiotic for three days prior to enrollment

         14. Use of antihistamines for one week prior to enrollment