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An Open-label Study to Identify Molecular Markers of Steroid Resistance (MERK2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Massachusetts General Hospital
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Massachusetts Eye and Ear Infirmary
Information provided by (Responsible Party):
Daniel Hamilos MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01616160
First received: May 30, 2012
Last updated: January 17, 2014
Last verified: January 2014

May 30, 2012
January 17, 2014
July 2013
December 2014   (final data collection date for primary outcome measure)
  • Steroid Sensitivity in vivo [ Time Frame: Change from pre-treatment symptom scores and nasal endoscopic findings after 4 weeks of treatment ] [ Designated as safety issue: No ]
    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 with MFNS.
  • Molecular Signature of mRNA [ Time Frame: 1 week ] [ Designated as safety issue: No ]
    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
  • Steroid sensitivity in vitro [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    To assess steroid sensitivity to mometasone furoate (MF) in cultured nasal polyp explant tissue in vitro.
Same as current
Complete list of historical versions of study NCT01616160 on ClinicalTrials.gov Archive Site
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An Open-label Study to Identify Molecular Markers of Steroid Resistance
An Open-label Study to Identify Molecular Markers of Steroid Resistance in Nasal Polyposis Before and Following Treatment With Mometasone Furoate (MFNS) 2 Sprays/Nostril (100 Mcg/Nostril) Twice Daily for 4 Weeks.

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.

Not Provided
Interventional
Phase 4
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Nasal Polyps
Drug: mometasone furoate
2 sprays/nostril BID
Other Name: Nasonex
Experimental: Nasal polyps subjects
24 subjects with nasal polyps
Intervention: Drug: mometasone furoate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
24
July 2015
December 2014   (final data collection date for primary outcome measure)

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
Both
21 Years to 70 Years
No
Contact: Lauren Tracy, BA 617-643-2262 letracy@partners.org
Contact: Daniel Hamilos, MD dhamilos@partners.org
United States
 
NCT01616160
2012P000387
Yes
Daniel Hamilos MD, Massachusetts General Hospital
Massachusetts General Hospital
  • Merck Sharp & Dohme Corp.
  • Massachusetts Eye and Ear Infirmary
Principal Investigator: Daniel Hamilos, MD Mass General Hospital
Massachusetts General Hospital
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP