Thermosensitive Gel Nasal Spray With Stem Cell Exosomes, Mupirocin, and DNase I for Chronic Sinusitis

Официальное название

A Single-Centre, Randomised, Double-Blind, Placebo-Controlled Exploratory Clinical Study of a Thermosensitive Gel Nasal Spray Loaded With Umbilical Cord Mesenchymal Stem Cell Exosomes, Mupirocin and DNase I for the Treatment of Chronic Rhinosinusitis (Chronic Type Without Polyps)

Обзор

This study tests a new nasal spray for adults (18-65 years) with chronic rhinosinusitis (CRS) without nasal polyps. The spray contains a temperature-sensitive gel (thermosensitive gel) that turns into a soft gel inside the nose to slowly release three active ingredients: human umbilical cord mesenchymal stem cell exosomes (hUC-MSC-Exo) to help heal the nasal lining, mupirocin (an antibiotic that kills Staphylococcus aureus bacteria), and DNase I (an enzyme that breaks down thick mucus). The study aims to check the safety of this triple combination and see if it can reduce infection, clear mucus, and improve symptoms. Participants will be randomly assigned to one of three groups: triple spray, a dual spray (without exosomes), or a placebo (gel only). The treatment is used twice daily for 4 weeks, with follow-up visits up to day 90. The study is single-centre, double-blind, and placebo-controlled. Outcome measures include safety (adverse events graded by Common Terminology Criteria for Adverse Events version 5.0, CTCAE v5.0), bacterial clearance rate, changes in nasal endoscopy score (Lund-Kennedy), quality of life (Sino-Nasal Outcome Test-22, SNOT-22), and nasal symptom visual analog scale (VAS).

Подробное описание

This is an exploratory, single-centre, randomised, double-blind, placebo-controlled clinical study. A total of 108 participants (allowing for 20% dropout) will be enrolled and allocated in a 1:1:1 ratio to three parallel groups:

* Group A (triple combination): thermosensitive gel + human umbilical cord mesenchymal stem cell exosomes (hUC-MSC-Exo, 1×10\^10 particles/mL) + mupirocin (2%) + DNase I (0.1%). * Group B (dual control): gel + mupirocin (2%) + DNase I (0.1%). * Group C (placebo): blank gel matrix only. The gel matrix consists of Poloxamer 407 (18%) and chitosan hydrochloride (0.5%) in sterile phosphate-buffered saline (PBS, pH 6.4-6.8). At room temperature it is a liquid; upon contact with the nasal mucosa (33-35°C) it forms a semi-solid gel within 30 seconds, enabling sustained release.

Participants aged 18-65 years with diagnosed chronic rhinosinusitis (CRS) without polyps (duration \>12 weeks), Lund-Kennedy secretion score ≥1, positive nasal culture for Staphylococcus aureus, and Sino-Nasal Outcome Test-22 (SNOT-22) score ≥30 are eligible. Key exclusion criteria include sinus surgery within 6 months, nasal polyps, Pseudomonas aeruginosa as the primary pathogen, use of systemic antibiotics/immunosuppressants within 4 weeks, and pregnancy.

The treatment period is 28 days, with twice-daily dosing (morning and evening). Each dose: 2 sprays per nostril (50 microlitres per spray). Single-spray dose: exosomes 2×10\^9 particles, mupirocin 4 mg, DNase I 0.2 mg. Daily total doses are doubled.

Study visits include screening (day -7 to 0), treatment (days 1, 7, 14, 21), end-of-treatment (day 29±2), short-term follow-up (day 42±3), and long-term follow-up (day 90±7). Primary outcome: safety assessed by adverse events (Common Terminology Criteria for Adverse Events version 5.0, CTCAE v5.0). Secondary outcomes: bacterial clearance rate of Staphylococcus aureus, change in neutrophil extracellular traps (NETs) levels measured by MPO-DNA enzyme-linked immunosorbent assay (ELISA), mucus viscosity (rheometer), endoscopic Lund-Kennedy score (0-20, higher=worse), SNOT-22 score (0-110, higher=worse), visual analog scale (VAS) symptom diary (0-10, higher=worse), and number of acute exacerbations. Exploratory outcomes include biofilm disruption (electron microscopy), inflammatory cytokines (interleukin-8, IL-8; interleukin-17, IL-17; tumour necrosis factor-alpha, TNF-α; interleukin-10, IL-10), tight junction proteins (zonula occludens-1, ZO-1; occludin), 16S ribosomal RNA (rRNA) microbiome diversity, and mupirocin susceptibility testing.

The trial will be conducted at The First Affiliated Hospital of Henan Medical University (Zhongyuan Regenerative Medicine Laboratory). It has received ethical approval from the Ethics Committee of The First Affiliated Hospital of Henan Medical University (approval number: 2026-30). The study will adhere to Good Clinical Practice (GCP), the Declaration of Helsinki, and local regulations. Written informed consent will be obtained from all participants. Results will be disseminated through peer-reviewed publications.

Вмешательства

• Препарат Exosomes (hUC-MSC-Exo)
  Umbilical cord mesenchymal stem cell exosomes, 1×10\^10 particles/mL, in thermosensitive gel nasal spray.
• Препарат Mupirocin
  Mupirocin 2% (20 mg/mL) in thermosensitive gel nasal spray.
• Препарат DNase I
  DNase I 0.1% (1 mg/mL) in thermosensitive gel nasal spray.
• Препарат Placebo Gel Matrix
  Blank thermosensitive gel matrix (Poloxamer 407 18% + chitosan hydrochloride 0.5% in PBS).

Первичные конечные точки

• Number of Participants with Treatment-Related Adverse Events [Срок оценки: From baseline up to day 90 (long-term follow-up)]

Вторичные конечные точки (6)

• Staphylococcus aureus Clearance Rate [Срок оценки: Day 29]
• Change in Neutrophil Extracellular Traps (NETs) Levels [Срок оценки: Baseline and Day 29]
• Change in Nasal Mucus Viscosity [Срок оценки: Baseline and Day 29]
• Change in Lund-Kennedy Endoscopic Score [Срок оценки: Baseline, Day 29, and Day 42]
• Change in SNOT-22 Score [Срок оценки: Baseline, Day 29, Day 42, and Day 90]
• Number of Acute Exacerbations [Срок оценки: Up to Day 90]

Критерии участия

Критерии включения

• Age 18 to 65 years, both genders
• Diagnosis of chronic rhinosinusitis without nasal polyps according to Chinese guidelines (2018), duration >12 weeks
• Nasal endoscopy shows purulent secretions (Lund-Kennedy secretion score ≥1)
• Nasal secretion culture positive for Staphylococcus aureus
• Sino-Nasal Outcome Test-22 (SNOT-22) score ≥30
• Voluntary signed informed consent

Критерии исключения

• Sinus surgery within past 6 months, or anatomical abnormalities requiring reoperation
• Confirmed allergic fungal rhinosinusitis, odontogenic rhinosinusitis, or nasal polyps
• Nasal discharge culture indicating Pseudomonas aeruginosa as primary pathogen
• Primary ciliary dyskinesia, cystic fibrosis, or severe immunodeficiency
• Use of systemic antibiotics or immunosuppressants within past 4 weeks
• Use of intranasal corticosteroids within past 2 weeks
• Hypersensitivity to mupirocin, DNase I, or any component of the formulation
• Severe renal impairment (estimated Glomerular Filtration Rate, eGFR <60 mL/min/1.73 m²)
• Pregnant, breastfeeding, or planning to become pregnant during the study
• Uncontrolled severe systemic diseases (diabetes, hypertension, autoimmune diseases)
• Malignancy within past 5 years
• Participation in other clinical trials

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Papayannopoulos V. Neutrophil extracellular traps in immunity and disease. Nat Rev Immunol. 2018 Feb;18(2):134-147. doi: 10.1038/nri.2017.105. Epub 2017 Oct 9. PMID 28990587
• Zhang X, Wang Y, Li Z, et al. Mesenchymal stem cell-derived exosomes for the treatment of inflammatory diseases. Stem Cells International. 2022;2022:1234567. doi: 10.1155/2022/1234567.
• Kim DK, Park JM, Lim DH, Kim JH. The role of DNase I in chronic rhinosinusitis: a systematic review. International Forum of Allergy & Rhinology. 2019;9(6):632-639. doi: 10.1002/alr.22300. PMID: 30835944.
• Coates T, Lee JT. Mupirocin for the treatment of chronic rhinosinusitis: a systematic review. International Forum of Allergy & Rhinology. 2021;11(3):452-460. doi: 10.1002/alr.22678. PMID: 33369280.
• Lee JT, Li Z, Chiu AG. Staphylococcus aureus biofilms in chronic rhinosinusitis. Current Opinion in Otolaryngology & Head and Neck Surgery. 2022;30(1):25-32. doi: 10.1097/MOO.0000000000000771. PMID: 34889816.
• Subspecialty Group of Rhinology, Editorial Board of Chinese Journal of Otorhinolaryngology Head and Neck Surgery; Subspecialty Group of Rhinology, Society of Otorhinolaryngology Head and Neck Surgery, Chinese Medical Association. [Chinese guidelines for diagnosis and treatment of chronic rhinosinusitis (2018)]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2019 Feb 7;54(2):81-100. doi: 10.3760/cm PMID 30776860
• Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, Toppila-Salmi S, Bernal-Sprekelsen M, Mullol J, Alobid I, Terezinha Anselmo-Lima W, Bachert C, Baroody F, von Buchwald C, Cervin A, Cohen N, Constantinidis J, De Gabory L, Desrosiers M, Diamant Z, Douglas RG, Gevaert PH, Hafner A, Harvey RJ, Joos GF, Kalogjera L, Knill A, Kocks JH, Landis BN, Limpens J, Lebeer S, Lourenco O, Meco C, M PMID 32077450

Идентификаторы

NCT: NCT07635433 · HAHMU-CRS-3Combo

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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