Investigating Sinonasal Inflammatory Profiles, Histopathological Features, and Remodeling Factors in Chronic Rhinosinusitis Patients With Nasal Polyposis
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Change in sinonasal inflammatory cytokine concentrations measured in nasal secretions using multiplex immunoassay
研究概览
简要总结
This study aims to examine three key aspects of chronic rhinosinusitis with nasal polyps (CRSwNP): inflammation, tissue structure (histopathology), and remodeling.
详细描述
By analyzing these tissue samples before and after treatment with intranasal corticosteroids (INCS), investiagtors hope to better understand how the nasal tissue changes and whether those changes are linked to improvements in symptoms. This information could help doctors create more personalized treatment plans for people with CRSwNP in the future.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be ≥19 of age at the time of signing the informed consent form
- •Capable of giving signed informed consent.
- •Having CRSwNP based on clinical symptoms and/or radiographic or endoscopic evidence of inflammation in their upper airways (Diagnosis consistent with EPOS 2020)2 and nasal polyp score (NPS) of at least 2 on each side
- •Not expecting to have surgery within the next 7 months
排除标准
- •A history of organ transplantation such as lung transplantation
- •Previously or currently using immunomodulator or allergy medications or (including The allergy medications such as: a) First and second generations of Antihistamines (H1 blockers); b) Oral/Topical Decongestants; c) Oral or systemic corticosteroids; d) Leukotriene Receptor Antagonists; e) Mast Cell Stabilizers.
- •Autoimmune medications such as: a) Systemic Steroids, b) Disease-modifying antirheumatic drugs (DMARDs) (non-biologic); c) Biologics such as anti-TNF, anti-IL, anti-B cell, anti-T cell; and d) Small molecules.
- •A history of auto-immune diseases such as Rheumatoid arthritis and Systemic lupus erythematosus,
- •Current or past sinonasal or bronchial tumors
- •Currently using systemic or oral corticosteroids (such as Prednisone, Methylprednisolone)
- •Current participation in any interventional treatment trials
- •Diagnosed or suspected malignant or premalignant nasal disease (e.g. Schniderian Papilloma, unilateral nasal polyposis)
- •Fungal rhinosinusitis (CT/Histology), positive Aspergillus skin prick testing and/or positive Aspergillus IgE RAST (Radioallergosorbent) testing
- •Malignant neoplasm within 5 years (from screening) excluding basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the uterinecervix treated locally and without metastatic disease for 3 years.
- •Active bleeding disorders, and/or inability to support interruption to anticoagulant or anti-platelet therapies for nasal biopsy.
- •Severe nasal deformity precluding endoscopic assessment/biopsy of postnasal space
- •Have an acute or chronic infection (excluding that related to CRS) requiring management as follows:
- •Currently on any treatment for a chronic infection such as pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria
- •Hospitalization solely for the treatment of proven infection requiring parenteral (IV or IM) antibiotics (antibacterial, antiviral, antifungal, or anti-parasitic agents) within 60 days of Day 1
- •Proven severe infection requiring outpatient treatment with parenteral (IV or IM) antibiotics (antibacterial, antiviral, antifungal, or anti-parasitic agents) within 60 days of Day
- •Prophylactic anti-infective treatment is allowed.
- •Known positive human immunodeficiency virus (HIV)** status
- •Known positive Hepatitis B (HB) or Hepatitis C* status
- •Having clinical evidence of significant unstable or uncontrolled acute or chronic diseases, in the opinion of the principal investigator, could confound the results of the study or put the participant at undue risk
- •Have a planned surgical procedure, laboratory abnormality, or condition that, in the opinion of the principal investigator, makes the participant unsuitable for the study.
- •Have received any investigational agent (that is not approved for sale in Canada) within 60 days of Day 1(Baseline visit)
- •Smoking history; current or former smokers with a smoke history of packs year >15
- •Subjects with parasitic (helminthic) infection Note: If there is any interested patient who is pregnant, breast-feeding or planning to get pregnant during the study period, and is interested in participation, the principal investigator will share the potential risks with them, as the drug crosses the placenta and is present in breast milk, before they decide to enroll in this study.
- •As these infectious diseases induce significant and distinct changes to the immune system and inflammatory profile.
研究组 & 干预措施
Budesonide
Participants will use budesonide for 6 months to treat CRSwNP
干预措施: Budesonide (Drug)
结局指标
主要结局
Change in sinonasal inflammatory cytokine concentrations measured in nasal secretions using multiplex immunoassay
时间窗: Baseline to 6 months
Sinonasal secretions will be collected via endoscopy-guided intranasal brushing using nasosorption sponges. Samples will be analyzed using the Luminex Bio-Plex Pro Human Cytokine Multiplex Assay and Luminex Human Magnetic Assay. Concentrations of inflammatory biomarkers will be quantified in pg/mL. The panel includes, but is not limited to: Interleukins (e.g., IL-4, IL-5, IL-6, IL-13) Interferon-gamma (IFN-γ) Transforming growth factor beta-1 (TGF-β1) Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) Monocyte chemoattractant protein (MCP) Macrophage inflammatory proteins (MIP) Chemokine ligands (CCLs) Granulocyte colony-stimulating factor (G-CSF) Granulocyte-macrophage colony-stimulating factor (GM-CSF) Myeloperoxidase (MPO) will be measured separately using enzyme-linked immunosorbent assay (ELISA)
Change in sinonasal histopathological score assessed using semi-quantitative histopathological evaluation of nasal biopsy specimens
时间窗: Baseline to 6 months
Nasal biopsy specimens will be analyzed using standard histopathological techniques, including hematoxylin and eosin (H\&E) staining. Histopathological features will be evaluated by a qualified pathologist using a predefined semi-quantitative scoring system. The following parameters will be assessed: inflammatory cell infiltration (eosinophils, neutrophils, lymphocytes), epithelial integrity and damage, goblet cell hyperplasia, basement membrane thickening, subepithelial fibrosis, and edema. Each parameter will be scored on a scale from 0 to 3 (0 = absent, 1 = mild, 2 = moderate, 3 = severe). Individual parameter scores will be summed to generate a total histopathological score, with higher scores indicating greater inflammation and tissue remodeling.
Remodeling features
时间窗: 6 months
Sinonasal remodeling features will be evaluated using nasal endoscopy and the Modified Lund-Kennedy (MLK) scoring system. The MLK scale assesses endoscopic findings including edema, discharge, crusting, and scarring. Each parameter is scored from 0 to 2 (0 = absent, 1 = mild, 2 = severe), with a total score ranging from 0 to 8. Higher scores indicate worse sinonasal disease severity and greater remodeling.
次要结局
- SNOT-22(6 months)
- Smell test(6 months)
研究者
Dr. Andrew Thamboo, MD
MD
St. Paul's Sinus Centre