Position-Directed Budesonide Nasal Drops for CRS-associated Olfactory Dysfunction

N/ANot Yet RecruitingNCT07386873

Peking University Third Hospital78 enrolled

Overview

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: 1. Efficacy Comparison: Is olfactory improvement greater with olfactory cleft-targeted steroid nasal drops compared to standard nasal steroid sprays in CRS patients? 2. Mechanism Exploration: How do changes in inflammatory markers, obstruction severity, and olfactory test results explain the potential benefits of this treatment approach? 3. Disease Classification: Can post-treatment olfactory dysfunction be categorized as fully reversible, partially reversible, or non-responsive/irreversible using Week-12 TDI recovery?

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.

Interventions

Nasal DropsDEVICE

Participants will receive budesonide suspension (2 mL:1 mg) as nasal drops, 20 drops per nostril twice daily (morning and evening) for 12 weeks. The drops will be administered in the Wu's position (Wu's 45° Head-Hanging Reclination Position), with the head suspended and tilted backward approximately 45° and the nostrils facing upward. The position will be maintained for approximately 5 minutes after instillation.

Nasal SprayDEVICE

Participants will administer conventional budesonide nasal spray in the standard upright sitting position according to routine clinical practice, 2 actuations per nostril once daily. Participants will be instructed to sniff gently after each spray. Treatment will continue for 12 weeks.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Men and women aged 18-65 years old. 2. Diagnosis of CRS according to the EPOS 2020, with olfactory dysfunction lasting ≥ 12 weeks. 3. 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. 4. Confirmation of OD via Sniffin' Sticks test: TDI score \<30.75 (hyposmia: 16 \< TDI \< 30.75; anosmia: TDI ≤ 16). 5. Sinus CT scan confirming olfactory cleft abnormalities (e.g., mucosal thickening, polypoid changes, obstruction). 6. Willingness to participate in this study and sign the informed consent form (ICF). Exclusion Criteria: 1. 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. 2. Patients with severe deviation of the nasal septum, nasal tumors, acute upper respiratory tract infection or uncontrolled allergic rhinitis. 3. 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. 4. Patients with current pregnancy or plan to become pregnant during the study period. 5. Patients with known hypersensitivity or contraindication to budesonide or any study medication component. 6. 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).

Outcomes

Primary Outcomes

Proportion of Participants with Clinically Meaningful Improvement in the Sniffin' Sticks test

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.

Time frame: Baseline, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, and 12 weeks after the initiation of treatment.

Secondary Outcomes

Subjective Olfactory Improvement and Nasal Symptoms

Patient-reported olfactory improvement measured using the Olfactory-Visual Analogue Scale (VAS) , 4-item Concise Aging adults Smell Test (4-CAST), nasal symptoms assessed via the Sino-Nasal Outcome Test 22 (SNOT-22) questionnaire, olfactory-related quality of life assessed via the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS), and Nasal Obstruction Symptom Evaluation (NOSE). These measures evaluate treatment effects on self-perceived smell recovery and associated nasal complaints.

Time frame: 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

Structural assessment of the olfactory cleft, including mucosal thickening, polypoid change/obstruction, and the protocol-defined olfactory cleft CT score, with a maximum total score of 24.

Time frame: Baseline , 4 weeks and 12 weeks after the initiation of treatment.

CFD Outcome

CFD-derived olfactory cleft airflow parameters Measure Description: Patient-specific computational fluid dynamics models will be reconstructed from sinus CT images to quantify olfactory cleft airflow velocity (m/s), volumetric flow rate (L/min), and olfactory cleft airflow ratio. These measures will be used as exploratory mechanistic and predictive variables.

Time frame: Baseline, 4 weeks and 12 weeks after the initiation of treatment.

Inflammatory Marker Levels in Olfactory Mucosa

Analysis of inflammatory cytokines via ELISA and single-cell sequencing from olfactory mucosal brush samples, with concurrent serum inflammatory marker testing.

Time frame: Baseline and 4 weeks after the initiation of treatment.

Adverse Event

Documentation of local (nasal irritation, epistaxis) and systemic steroid-related adverse events using standardized case report forms during all follow-up visits.

Time frame: 1 week, and 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, and 12 weeks after the initiation of treatment.

Post-treatment Olfactory Reversibility Classification

At Week 12, participants will be categorized as: Fully reversible: final TDI score ≥30.75; Partially reversible: TDI score increases by ≥5.5 points from baseline but remains \<30.75; Non-responsive/irreversible: TDI score increases by \<5.5 points from baseline.

Time frame: 12 weeks after the initiation of treatment.