Thermosensitive Gel Nasal Spray With Exosomes, Azelastine, and Interferon for Acute Phase of Chronic Sinusitis

Официальное название

A Single-Centre, Randomised, Double-Blind, Placebo-Controlled Exploratory Clinical Study of a Thermosensitive Gel Nasal Spray Containing Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes, Azelastine and Recombinant Human Interferon α-2b for the Treatment of Chronic Rhinosinusitis (Acute Phase)

Обзор

This study tests a new nasal spray for adults (18-65 years) with chronic sinusitis experiencing an acute phase. The spray contains a temperature-sensitive gel that turns into a soft gel inside the nose to slowly release three active ingredients: stem cell exosomes (to repair nasal lining), azelastine (an antihistamine and anti-inflammatory drug), and interferon alpha-2b (an antiviral agent). The study aims to evaluate safety and see if the spray can reduce symptoms, fight viruses, and improve quality of life. Participants will be randomly assigned to one of three groups: triple spray, dual spray (without exosomes), or placebo (gel only). Treatment is twice daily for 4 weeks, with follow-up visits up to day 90.

Подробное описание

This exploratory, single-centre, randomised, double-blind, placebo-controlled study enrolls 108 participants (allowing 20% dropout) in a 1:1:1 ratio. Group A receives thermosensitive gel + exosomes (1×10\^10 particles/mL) + azelastine (0.1%) + interferon α-2b (1×10\^5 IU/mL). Group B receives gel + azelastine + interferon (without exosomes). Group C receives blank gel. The gel matrix (Poloxamer 407 18% + chitosan hydrochloride 0.5%) is liquid at room temperature and gels at nasal temperature (33-35°C). Treatment duration is 28 days (twice daily, 2 sprays per nostril). Single-spray doses: exosomes 2×10\^9 particles, azelastine 0.2 mg, interferon 2000 IU. Follow-up at day 42 and day 90. Primary outcome: safety (adverse events, CTCAE v5.0). Secondary outcomes: Lund-Kennedy score, SNOT-22, VAS, response rate, SF-36. Exploratory: viral clearance, inflammatory cytokines, bacterial load, mucosal barrier markers. The study is conducted at The First Affiliated Hospital of Xinxiang Medical College. Ethics approval obtained. Results will be published.

Вмешательства

• Препарат Exosomes, Azelastine, and Interferon alpha-2b
  Thermosensitive gel nasal spray containing hUC-MSC-Exos (1×10\^10 particles/mL), azelastine hydrochloride 0.1%, and interferon α-2b 1×10\^5 IU/mL.
• Препарат Azelastine and Interferon alpha-2b
  Thermosensitive gel nasal spray containing azelastine hydrochloride 0.1% and interferon α-2b 1×10\^5 IU/mL.
• Препарат Placebo Gel Matrix
  Thermosensitive gel matrix (Poloxamer 407 18% + chitosan hydrochloride 0.5% in PBS) only.

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 (5)

• 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]
• Change in VAS Symptom Score (nasal congestion, rhinorrhoea, facial pressure, smell loss) [Срок оценки: Daily during treatment (Days 1-28) and follow-up up to Day 90]
• Response Rate (SNOT-22 improvement ≥15 points or ≥50%) [Срок оценки: Day 29]
• Change in Quality of Life (SF-36) [Срок оценки: Baseline and Day 29]

Критерии участия

Критерии включения

• Age 18 to 65 years, both genders
• Diagnosis of chronic rhinosinusitis according to Chinese guidelines (2018) or EPOS 2020, duration >12 weeks
• Lund-Kennedy endoscopic score ≥4
• SNOT-22 score ≥30
• Nasal symptoms stable in past month, or acute flare-ups not requiring systemic antibiotics/steroids
• Voluntary signed informed consent

Критерии исключения

• Sinus surgery within past 6 months or anatomical abnormalities requiring reoperation
• Allergic fungal rhinosinusitis, odontogenic rhinosinusitis, or nasal polyps
• Primary ciliary dyskinesia, cystic fibrosis, or severe immunodeficiency
• Use of systemic glucocorticoids, immunosuppressants, or antibiotics within past 4 weeks
• Use of intranasal glucocorticoids, antihistamines, or leukotriene receptor antagonists within past 2 weeks
• Hypersensitivity to poloxamer, chitosan, azelastine, or interferon
• Pregnant, breastfeeding, or planning to become pregnant
• 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

• 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.
• Gurwitz D. Human interferon alpha-2b: a topical antiviral for the treatment of COVID-19 and other respiratory viral infections. Drug Development Research. 2020;81(7):783-785. doi: 10.1002/ddr.21718.
• Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020 Feb 7;367(6478):eaau6977. doi: 10.1126/science.aau6977. PMID 32029601
• Buzas EI. The roles of extracellular vesicles in the immune system. Nat Rev Immunol. 2023 Apr;23(4):236-250. doi: 10.1038/s41577-022-00763-8. Epub 2022 Aug 4. PMID 35927511
• 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: NCT07635459 · HAHMU-CRS-AP-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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