Position-Directed Budesonide Nasal Drops for Olfactory Dysfunction in Eosinophilic Chronic Rhinosinusitis: A Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Proportion of Participants with Clinically Meaningful Improvement in the Sniffin' Sticks test
研究概览
简要总结
This single-center randomized controlled trial evaluates whether budesonide nasal drops delivered in the Wu's position (Wu's 45° Head-Hanging Reclination Position) improve olfactory function more effectively than conventional budesonide nasal spray in adults with type 2 chronic rhinosinusitis (CRS)-related olfactory dysfunction.
The study also evaluates patient-reported symptoms and quality of life, olfactory cleft structural abnormalities on sinus CT, computational fluid dynamics (CFD)-derived airflow parameters, safety, and whether baseline peripheral blood eosinophil count and clinical phenotype predict treatment response.
The main questions this clinical trial aims to answer are:
- Efficacy Comparison: Is olfactory improvement greater with olfactory cleft-targeted steroid nasal drops compared to standard nasal steroid sprays in CRS patients?
- Mechanism Exploration: How do changes in inflammatory markers, obstruction severity, and olfactory test results explain the potential benefits of this treatment approach?
- Disease Classification: Can post-treatment olfactory dysfunction be categorized as fully reversible, partially reversible, or non-responsive/irreversible using Week-12 TDI recovery?
详细描述
Chronic rhinosinusitis (CRS)-related olfactory dysfunction may result from both obstruction of the olfactory cleft and persistent local inflammation. Conventional intranasal corticosteroid sprays may have limited and variable drug deposition in the olfactory cleft. This randomized controlled trial is designed to evaluate whether targeted delivery of budesonide nasal drops using the Wu's position (Wu's 45° Head-Hanging Reclination Position) provides greater olfactory improvement than conventional budesonide nasal spray in patients with eosinophilic/type 2 CRS-related olfactory dysfunction.
A total of 78 adults aged 18-65 years will be randomized 1:1 to receive either budesonide nasal drops administered in the Wu's position or conventional budesonide nasal spray for 12 weeks. Participants in the nasal-drop group will receive budesonide suspension, 20 drops per nostril twice daily, and will maintain the Wu's position for approximately 5 minutes after administration. Participants in the control group will receive conventional budesonide nasal spray, 2 actuations per nostril once daily in the upright sitting position.
Olfactory function will be assessed using Sniffin' Sticks, including odor threshold, discrimination, identification, and the composite TDI score. The primary outcome is the proportion of participants achieving a clinically meaningful TDI improvement of ≥5.5 points at Week 12. Additional assessments will include the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS), Olfactory-Visual Analogue Scale (VAS), the Sino-Nasal Outcome Test 22 (SNOT-22), Nasal Obstruction Symptom Evaluation (NOSE), and 4-item Concise Aging adults Smell Test (4-CAST). Sinus CT will be used to evaluate olfactory cleft structural abnormalities, while computational fluid dynamics (CFD) analysis will characterize olfactory cleft airflow.
At Week 12, olfactory recovery will also be classified as fully reversible, partially reversible, or non-responsive/irreversible according to the magnitude and completeness of TDI improvement. Baseline olfactory cleft CT findings, CFD-derived airflow parameters, peripheral blood eosinophil count, nasal polyp status, olfactory severity, and other clinical assessment scores will be explored as potential predictors of treatment response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women aged 18-65 years old.
- •Diagnosis of CRS according to the EPOS 2020, with olfactory dysfunction lasting ≥ 12 weeks.
- •Evidence of eosinophilic/type 2 inflammatory CRS, defined by at least one of the following: JESREC score ≥11, peripheral blood eosinophils ≥5%, absolute blood eosinophil count ≥ 0.25 × 10⁹/L.
- •Confirmation of OD via Sniffin' Sticks test: TDI score <30.75 (hyposmia: 16 < TDI < 30.75; anosmia: TDI ≤ 16).
- •Sinus CT scan confirming olfactory cleft abnormalities (e.g., mucosal thickening, polypoid changes, obstruction).
- •Willingness to participate in this study and sign the informed consent form (ICF).
排除标准
- •Patients who have used systemic corticosteroids within the past 4 weeks or who have used intranasal corticosteroids within the past 2 weeks, or biologic therapy targeting type 2 inflammation within 6 months before enrolment.
- •Patients with severe deviation of the nasal septum, nasal tumors, acute upper respiratory tract infection or uncontrolled allergic rhinitis.
- •Patients with severe cardiovascular diseases, liver or kidney dysfunction, uncontrolled diabetes, or immune system disorders or other systemic disease that may interfere with study participation or safety.
- •Patients with current pregnancy or plan to become pregnant during the study period.
- •Patients with known hypersensitivity or contraindication to budesonide or any study medication component.
- •Patients who are unable to complete the study or are unable to comply with the requirements of the study (including inability to tolerate olfactory function testing and treatment, memory or behavioral abnormalities, depression, smoking, heavy alcohol use or prior non-compliance, specifically early withdrawal from a study).
研究组 & 干预措施
Nasal Drops Group
干预措施: Nasal Drops (Device)
Standard Nasal Spray Group
干预措施: Nasal Spray (Device)
结局指标
主要结局
Proportion of Participants with Clinically Meaningful Improvement in the Sniffin' Sticks test
时间窗: Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, and 12 weeks after the initiation of treatment.
Proportion of participants achieving a clinically meaningful improvement in Sniffin' Sticks TDI score at Week 12. A responder is defined as a participant with an increase in the composite TDI score of ≥5.5 points from baseline. The TDI score is calculated as the sum of odor Threshold (T), Discrimination (D), and Identification (I) scores.
The Sniffin' Sticks test
时间窗: Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, and 12 weeks after the initiation of treatment.
A clinically significant olfactory improvement as measured by Sniffin' Sticks threshold, discrimination, and identification(TDI)
次要结局
- Subjective Olfactory Improvement and Nasal Symptoms(Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, and 12 weeks after the initiation of treatment.)
- CT Evaluation of Olfactory Cleft Blockage(Baseline , 4 weeks and 12 weeks after the initiation of treatment.)
- CFD Outcome(Baseline, 4 weeks and 12 weeks after the initiation of treatment.)
- Post-treatment Olfactory Reversibility Classification(12 weeks after the initiation of treatment.)
- Subjective Olfactory Improvement and Nasal Symptoms(1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, and 12 weeks after the initiation of treatment.)
- CT Evaluation of Olfactory Cleft Blockage(Baseline and 4 weeks after the initiation of treatment.)
- Inflammatory Marker Levels in Olfactory Mucosa(Baseline and 4 weeks after the initiation of treatment.)
- Adverse Event(1 week, and 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, and 12 weeks after the initiation of treatment.)
研究者
Dawei Wu
Associate Researcher
Peking University Third Hospital