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

NCT01616160 | Terminated Phase 4 Results DMC

• 1 other identifier: 2012P000387
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Nasal Polyps

Keywords

Nasal polyps

Outcome Measures

Primary Outcomes (2)

• Change in Steroid Sensitivity in Vivo Symptom Scores - Trouble With Sense of Smell

  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.

  Change between pre- and post-treatment symptom score after 4 weeks of treatment

• Change in Steroid Sensitivity in Vivo Nasal Endoscopy Polyp Scores

  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.

  Change between pre- and post-treatment symptom score after 4 weeks of treatment

Study Arms (1)

Nasal polyps subjects

EXPERIMENTAL

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

Interventions

mometasone furoate DRUG

2 sprays/nostril BID

Also known as: Nasonex

Nasal polyps subjects

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- The subject must fulfill all of the following conditions or characteristics to be considered for enrollment:
• Male or female between ages 21 - 70 years residing in the Boston area
• 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
• Abnormal CT scan in at least 2 sinuses areas within 3 months
• Evidence of bilateral polyps or polypoid mucosa (on nasal endoscopy) with minimum polyp/polypoid score of 4 (see scoring system below).

You may not qualify if:

• \. History of suggestive of immunodeficiency (i.e. those who have had \> one pneumonia in the past 12 months or those with known immune deficiency).
• History of cystic fibrosis, Kartagener's syndrome, immotile cilia syndrome, hypogammaglobulinemia or bleeding disorder
• URI within six weeks prior to enrollment
• Intranasal cocaine use
• Pregnancy (if applicable
• History of fainting
• Use of prescription blood thinners
• Use of systemic glucocorticoids for two weeks prior to enrollment
• Use of intranasal corticosteroids and anticholinergics for three days prior to enrollment
• Use of an antibiotic for three days prior to enrollment
• Use of antihistamines for one week prior to enrollment

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Merck Sharp & Dohme LLC: collaborator
• Massachusetts Eye and Ear Infirmary: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Nasal Polyps

Interventions

Mometasone Furoate

Condition Hierarchy (Ancestors)

Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Daniel L. Hamilos, M.D.
• Organization: Massachusetts General Hospital

dhamilos@partners.org

617-726-5090

Study Officials

• Daniel Hamilos, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: May 30, 2012
• First Posted: June 11, 2012
• Study Start: July 1, 2013
• Primary Completion: January 1, 2017
• Study Completion: January 9, 2018
• Last Updated: June 12, 2018
• Results First Posted: June 12, 2018

Record last verified: 2018-05

Locations

US (1)