Thermosensitive Gel Nasal Spray With Stem Cell Exosomes, Mupirocin, and DNase I for Chronic Sinusitis
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)
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).
調査の概要
状態
まだ募集していません
詳細な説明
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.
研究の種類
介入
入学 (推定)
108
段階
- 初期フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Wenfa Yu, MD, PhD
- 電話番号：86+15516510606
- メール：yuwenfa197288@aliyun.com
研究連絡先のバックアップ
- 名前：Wenjie Ren, MD, PhD
- 電話番号：86+13937354075
- メール：13937354075@163.com
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
説明
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Triple Combination (Exosomes + Azelastine + Interferon)
Participants receive the thermosensitive gel nasal spray containing human umbilical cord mesenchymal stem cell exosomes (hUC-MSC-Exo, 1×10^10 particles/mL), mupirocin (2%), and DNase I (0.1%).
Two sprays per nostril, twice daily for 28 days.
|
Umbilical cord mesenchymal stem cell exosomes, 1×10^10 particles/mL, in thermosensitive gel nasal spray.
Mupirocin 2% (20 mg/mL) in thermosensitive gel nasal spray.
DNase I 0.1% (1 mg/mL) in thermosensitive gel nasal spray.
|
|
アクティブコンパレータ：Triple Combination (Exosomes + Mupirocin + DNase I)
Participants receive the thermosensitive gel nasal spray containing mupirocin (2%) and DNase I (0.1%).
Two sprays per nostril, twice daily for 28 days.
|
Mupirocin 2% (20 mg/mL) in thermosensitive gel nasal spray.
DNase I 0.1% (1 mg/mL) in thermosensitive gel nasal spray.
|
|
プラセボコンパレーター：Placebo (Gel Matrix Only)
Participants receive the blank thermosensitive gel matrix (Poloxamer 407 18% + chitosan hydrochloride 0.5% in PBS) without active ingredients.
Two sprays per nostril, twice daily for 28 days.
|
Blank thermosensitive gel matrix (Poloxamer 407 18% + chitosan hydrochloride 0.5% in PBS).
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Number of Participants with Treatment-Related Adverse Events
時間枠：From baseline up to day 90 (long-term follow-up)
|
Local adverse events (epistaxis, nasal irritation, burning sensation, dryness), systemic adverse events (headache, nausea, allergic reactions), and changes in laboratory parameters (complete blood count, liver function, kidney function) graded according to CTCAE Version 5.0.
|
From baseline up to day 90 (long-term follow-up)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Staphylococcus aureus Clearance Rate
時間枠：Day 29
|
Proportion of participants with negative nasal culture for Staphylococcus aureus at end of treatment.
|
Day 29
|
|
Change in Neutrophil Extracellular Traps (NETs) Levels
時間枠：Baseline and Day 29
|
Measured by MPO-DNA complex ELISA in nasal lavage fluid.
|
Baseline and Day 29
|
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Change in Nasal Mucus Viscosity
時間枠：Baseline and Day 29
|
Assessed by rotational rheometer.
|
Baseline and Day 29
|
|
Change in Lund-Kennedy Endoscopic Score
時間枠：Baseline, Day 29, and Day 42
|
Lund-Kennedy Endoscopic Score.
Minimum value 0 (normal), maximum value 20 (most severe inflammation).
Higher scores mean a worse outcome.
This scale assesses polyps, oedema, discharge, scarring, and crusting.
The score is used to evaluate nasal mucosal inflammation.
|
Baseline, Day 29, and Day 42
|
|
Change in SNOT-22 Score
時間枠：Baseline, Day 29, Day 42, and Day 90
|
Sino-Nasal Outcome Test-22 (SNOT-22) Score.
Minimum value 0 (no symptoms), maximum value 110 (worst possible symptoms).
Higher scores mean a worse outcome.
It measures symptom severity and quality of life in patients with chronic rhinosinusitis.
|
Baseline, Day 29, Day 42, and Day 90
|
|
Number of Acute Exacerbations
時間枠：Up to Day 90
|
Number of acute exacerbations requiring antibiotic or steroid treatment within 3 months of follow-up.
|
Up to Day 90
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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, Matricardi PM, O'Mahony L, Philpott CM, Ryan D, Schlosser R, Senior B, Smith TL, Teeling T, Tomazic PV, Wang DY, Wang D, Zhang L, Agius AM, Ahlstrom-Emanuelsson C, Alabri R, Albu S, Alhabash S, Aleksic A, Aloulah M, Al-Qudah M, Alsaleh S, Baban MA, Baudoin T, Balvers T, Battaglia P, Bedoya JD, Beule A, Bofares KM, Braverman I, Brozek-Madry E, Richard B, Callejas C, Carrie S, Caulley L, Chussi D, de Corso E, Coste A, El Hadi U, Elfarouk A, Eloy PH, Farrokhi S, Felisati G, Ferrari MD, Fishchuk R, Grayson W, Goncalves PM, Grdinic B, Grgic V, Hamizan AW, Heinichen JV, Husain S, Ping TI, Ivaska J, Jakimovska F, Jovancevic L, Kakande E, Kamel R, Karpischenko S, Kariyawasam HH, Kawauchi H, Kjeldsen A, Klimek L, Krzeski A, Kopacheva Barsova G, Kim SW, Lal D, Letort JJ, Lopatin A, Mahdjoubi A, Mesbahi A, Netkovski J, Nyenbue Tshipukane D, Obando-Valverde A, Okano M, Onerci M, Ong YK, Orlandi R, Otori N, Ouennoughy K, Ozkan M, Peric A, Plzak J, Prokopakis E, Prepageran N, Psaltis A, Pugin B, Raftopulos M, Rombaux P, Riechelmann H, Sahtout S, Sarafoleanu CC, Searyoh K, Rhee CS, Shi J, Shkoukani M, Shukuryan AK, Sicak M, Smyth D, Sindvongs K, Soklic Kosak T, Stjarne P, Sutikno B, Steinsvag S, Tantilipikorn P, Thanaviratananich S, Tran T, Urbancic J, Valiulius A, Vasquez de Aparicio C, Vicheva D, Virkkula PM, Vicente G, Voegels R, Wagenmann MM, Wardani RS, Welge-Lussen A, Witterick I, Wright E, Zabolotniy D, Zsolt B, Zwetsloot CP. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020 Feb 20;58(Suppl S29):1-464. doi: 10.4193/Rhin20.600.
- 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/cma.j.issn.1673-0860.2019.02.001. No abstract available. Chinese.
- 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.
- 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.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年7月1日
一次修了 (推定)
2027年6月30日
研究の完了 (推定)
2027年6月30日
試験登録日
最初に提出
2026年5月30日
QC基準を満たした最初の提出物
2026年6月7日
最初の投稿 (実際)
2026年6月9日
学習記録の更新
投稿された最後の更新 (実際)
2026年6月9日
QC基準を満たした最後の更新が送信されました
2026年6月7日
最終確認日
2026年6月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- HAHMU-CRS-3Combo
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
いいえ
IPD プランの説明
This is a single-centre exploratory study with a small sample size (N=108).
The data contain sensitive participant information and are subject to local privacy regulations.
No formal data sharing agreement is planned.
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
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