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

This study is not yet open for participant recruitment.
Verified May 2013 by Massachusetts General Hospital
Sponsor:
Collaborators:
Merck
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: May 15, 2013
Last verified: May 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Nasal Polyps
 Drug: mometasone furoate
 Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: 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.

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 24
Study Start Date: July 2013
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nasal polyps subjects
24 subjects with nasal polyps
 Drug: mometasone furoate
2 sprays/nostril BID
Other Name: Nasonex

  Eligibility

Ages Eligible for Study:   21 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01616160

Contacts
Contact: Lauren Tracy, BA 617-643-2262 letracy@partners.org
Contact: Daniel Hamilos, MD dhamilos@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Lauren Tracy, BA     617-643-2262     letracy@partners.org    
Principal Investigator: Daniel Hamilos, MD            
Sponsors and Collaborators
Massachusetts General Hospital
Merck
Massachusetts Eye and Ear Infirmary
Investigators
Principal Investigator: Daniel Hamilos, MD Mass General Hospital
  More Information

No publications provided

Responsible Party: Daniel Hamilos MD, Principle Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01616160     History of Changes
Other Study ID Numbers: 2012P000387
Study First Received: May 30, 2012
Last Updated: May 15, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Nasal polyps

Additional relevant MeSH terms:
Nasal Polyps
Polyps
Nose Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Pathological Conditions, Anatomical
 Mometasone furoate
Anti-Allergic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on May 19, 2013