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

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ClinicalTrials.gov Identifier: NCT01616160
Recruitment Status : Terminated (Inability to recruit additional subjects.)
First Posted : June 11, 2012
Results First Posted : June 12, 2018
Last Update Posted : June 12, 2018
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Massachusetts Eye and Ear Infirmary
Information provided by (Responsible Party):
Daniel Hamilos MD, Massachusetts General Hospital

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

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 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
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 9, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nasal polyps subjects
24 subjects with nasal polyps. Intervention: Each subject will receive Nasonex (mometasone furoate) 2 spray per nostril twice daily for 4 weeks.
Drug: mometasone furoate
2 sprays/nostril BID
Other Name: Nasonex




Primary Outcome Measures :
  1. Change in Steroid Sensitivity in Vivo Symptom Scores - Trouble With Sense of Smell [ Time Frame: Change between pre- and post-treatment symptom score after 4 weeks of treatment ]
    To assess steroid sensitivity in subjects comparing Trouble with sense of smell symptom scores before and following 4 weeks treatment with mometasone furoate nasal spray (MFNS). Trouble with sense of smell measured on 0 to 4 scale ( 0 = no trouble with smell; 4 = severe trouble with smell). The outcome is the difference in mean score (Post - Pre). A negative difference would indicate patients had less trouble with sense of smell at the end of the study.

  2. Change in Steroid Sensitivity in Vivo Nasal Endoscopy Polyp Scores [ Time Frame: Change between pre- and post-treatment symptom score after 4 weeks of treatment ]
    To assess steroid sensitivity in subjects comparing nasal endoscopy polyp score before and following 4 weeks treatment with mometasone furoate nasal spray (MFNS). Nasal endoscopic polyp score measured on 0 to 4 scale ( 0 = no nasal polyp; 1 = polyp in the middle meatus, not below the inferior border of the middle turbinate (MT); 2 = polyp below the inferior border of the MT but not touching the inferior turbinate (IT); 3 = polyp below the inferior border of the MT and touching the IT; 4 = polyp to or below the lower border of the IT). The outcome is the difference in mean score (Post - Pre). A negative difference would indicate that patients had a reduction in nasal polyp size at the end of the study.



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Ages Eligible for Study:   21 Years to 70 Years   (Adult, Older Adult)
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

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


Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Merck Sharp & Dohme Corp.
Massachusetts Eye and Ear Infirmary
Investigators
Principal Investigator: Daniel Hamilos, MD Mass General Hospital

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
Results First Posted: June 12, 2018
Last Update Posted: June 12, 2018
Last Verified: May 2018

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