We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01616160
Recruitment Status : Unknown
Verified January 2014 by Daniel Hamilos MD, Massachusetts General Hospital.
Recruitment status was:  Recruiting
First Posted : June 11, 2012
Last Update Posted : January 22, 2014
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
Brief 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.


Condition or disease Intervention/treatment Phase
Nasal Polyps Drug: mometasone furoate Phase 4

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (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.
Study Start Date : July 2013
Estimated Primary Completion Date : December 2014
Estimated Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Nasal polyps subjects
24 subjects with nasal polyps
Drug: mometasone furoate
2 sprays/nostril BID
Other Name: Nasonex


Outcome Measures

Primary Outcome Measures :
  1. Steroid Sensitivity in vivo [ Time Frame: Change from pre-treatment symptom scores and nasal endoscopic findings after 4 weeks of treatment ]
    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.

  2. Molecular Signature of mRNA [ Time Frame: 1 week ]
    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

  3. Steroid sensitivity in vitro [ Time Frame: 24 hours ]
    To assess steroid sensitivity to mometasone furoate (MF) in cultured nasal polyp explant tissue in vitro.


Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   21 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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 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 Sharp & Dohme Corp.
Massachusetts Eye and Ear Infirmary
Investigators
Principal Investigator: Daniel Hamilos, MD Mass General Hospital
More Information

Responsible Party: Daniel Hamilos MD, Principle Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01616160     History of Changes
Other Study ID Numbers: 2012P000387
First Posted: June 11, 2012    Key Record Dates
Last Update Posted: January 22, 2014
Last Verified: January 2014

Keywords provided by Daniel Hamilos MD, Massachusetts General Hospital:
Nasal polyps

Additional relevant MeSH terms:
Nasal Polyps
Nose Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Polyps
Pathological Conditions, Anatomical
Mometasone Furoate
Anti-Inflammatory Agents
Dermatologic Agents
Anti-Allergic Agents