An Open-label Study to Identify Molecular Markers of Steroid Resistance

• Status: Terminated
• Trial end date: 2018-01-09
• Target enrollment: 0
• Participant gender: All

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
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Collaborators: Massachusetts Eye and Ear Infirmary; Merck Sharp & Dohme Corp.
• Treatments: Mometasone Furoate

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