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.
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Change in Steroid Sensitivity in Vivo Symptom Scores - Trouble With Sense of Smell
研究概览
简要总结
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.
详细描述
Visit 1: Baseline evaluation and nasal endoscopy
At this visit, each subject will sign an informed consent, the subject's eligibility for the study will be confirmed, a medical history will be obtained, the subject will undergo a physical examination and nasal endoscopy. A urine pregnancy test will be performed on all females of childbearing potential. NP size will be recorded using the NP scoring system (see below).
Allergy skin testing will only be performed if it has not been done in the past 3 years.
Visit 2: Pre-treatment nasal polyp (NP) biopsies
At this visit, each subject will undergo the pre-treatment NP biopsies. The biopsies will be obtained by Dr. Eric Holbrook at Massachusetts Eye & Ear Infirmary, located adjacent to MGH.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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
- •MEDICATION EXCLUSIONS prior to NP biopsies:
- •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
研究组 & 干预措施
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.
干预措施: mometasone furoate (Drug)
结局指标
主要结局
Change in Steroid Sensitivity in Vivo Symptom Scores - Trouble With Sense of Smell
时间窗: 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.
Change in Steroid Sensitivity in Vivo Nasal Endoscopy Polyp Scores
时间窗: 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.
次要结局
未报告次要终点
研究者
Daniel Hamilos MD
Principle Investigator
Massachusetts General Hospital