Topical Versus Injection PRP for Olfactory Dysfunction

Официальное название

Carrier-Assisted Topical Application Versus Intranasal Injection of Autologous Platelet-Rich Plasma for Olfactory Dysfunction: A Randomized Controlled Trial

Обзор

The goal of this clinical trial is to determine whether two different delivery methods of autologous platelet-rich plasma (PRP) can improve olfactory function in adults with persistent olfactory dysfunction lasting more than three months. The main questions it aims to answer are: 1. Does carrier-assisted topical application of PRP lead to comparable or better improvement in smell function than intranasal injection of PRP? 2. Which method provides greater patient comfort and fewer adverse effects? Researchers will compare carrier-assisted topical PRP application to intranasal PRP injection to see if one approach is more effective in restoring olfactory function. Participants will: 1. Receive a single PRP treatment delivered either by injection or via a PRP-soaked carrier placed into the olfactory cleft. 2. Continue daily olfactory training for three months following the intervention. 3. Undergo smell testing (Sniffin' Sticks) before and after treatment and complete quality-of-life questionnaires.

Подробное описание

Persistent olfactory dysfunction (OD) is a common sequela of viral upper respiratory tract infections, including COVID-19, and can significantly affect patients' quality of life, nutrition, and safety. Current treatment options are limited, with olfactory training being the primary evidence-based non-pharmacological therapy. Autologous platelet-rich plasma (PRP) is a concentration of platelets obtained from a patient's own blood, rich in growth factors and cytokines that promote neuronal regeneration, tissue repair, and neuroplasticity. Early clinical studies suggest PRP may improve olfactory function, but the optimal method for delivering PRP to the olfactory cleft remains unknown.

This randomized controlled trial will include a total of 60 adult patients aged 18-80 years old with olfactory loss (hyposmia or anosmia) persisting for more than 3 months despite standardized olfactory training, confirmed by a reduced Sniffin' Sticks TDI score.

PRP will be prepared on-site immediately before application using a standardized centrifugation protocol to achieve a platelet concentration 2-3 times above baseline. efficacy and safety of two PRP delivery methods will be compared:

Intranasal Injection Group: Autologous PRP will be injected directly into the mucosa of the olfactory cleft under endoscopic guidance. After topical anesthesia with lidocaine spray and decongestion with oxymetazoline, a 25-gauge needle will be used to deliver approximately 1 mL of PRP into multiple sites along the superior nasal cavity bilaterally.

Carrier-Assisted Topical Application Group: Four pieces of sterile, bioabsorbable carrier (Gelfoam sponge) will be soaked with approximately 5 mL of autologous PRP. Under endoscopic guidance, two pieces of PRP-soaked carrier will be placed gently into each side of olfactory cleft, ensuring contact with the olfactory mucosa. Carriers will remain in place for a short duration to allow diffusion of PRP before dissolving naturally or being removed.

Primary Outcome: Change in TDI score from baseline to 3 months post-treatment.

Secondary Outcomes: Patient-reported olfactory-related quality of life (QOD, SNOT-22, PQ), subjective improvement ratings, 20-item retronasal olfactory test, SSParoT, procedure tolerability, and adverse event rates.

Post-intervention care: All participants will continue standardized daily olfactory training for at least 12 weeks after PRP administration. Follow-up visits at 2 weeks, 1 month and 3 months will assess smell function, symptom changes, and safety.

This study aims to determine whether carrier-assisted topical PRP application is as effective or superior to intranasal PRP injection for improving olfactory function, while potentially offering a less invasive and more tolerable treatment approach. Results will help define optimal PRP delivery strategies for olfactory rehabilitation in clinical practice.

Вмешательства

• Процедура Intranasal Injection of Autologous PRP
  Under topical anesthesia and decongestion, approximately 1 mL of freshly prepared autologous platelet-rich plasma will be injected into multiple sites of the olfactory cleft mucosa bilaterally using a 25-gauge needle under endoscopic guidance. Single treatment session.
• Процедура Carrier-Assisted Topical Application of Autologous PRP
  Four pieces of sterile, bioabsorbable carrier (Gelfoam sponge) will be soaked with approximately 5 mL of freshly prepared autologous platelet-rich plasma. Under endoscopic guidance, two pieces will be placed gently into each olfactory cleft, ensuring contact with the olfactory mucosa. Carriers will remain briefly to allow PRP diffusion before dissolving naturally or being removed. Single treatment session.
• Комбинированный продукт platelet-rich plasma
  This study adopts a fully automated, closed-system PRP preparation technique to ensure the stability of the blood product. A total of 60 mL of whole blood is drawn and processed using the Phoenix Q1 centrifuge (TFDA Medical Device Manufacturing License No. 004461) for blood component separation in a closed, sterile environment. An optical sensor identifies and automatically collects the buffy coat layer (rich in platelets and monocytes), yielding approximately 6 mL of autologous platelet-rich pl
• Устройство olfactory training
  Participants will perform olfactory training for 12 weeks following the PRP intervention. Training is conducted twice daily using four odor bottles containing standardized odorants from Sigma-Aldrich (Germany): lemon (citronellal, #27470), rose (phenylethanol, #77861), clove (eugenol, #W246700), and eucalyptus (eucalyptol, #C80601). Each odor is sniffed gently for about 20 seconds, with a 20-second pause between bottles. Participants will record the perceived intensity of each odor in a training

Первичные конечные точки

• Sniffin' Sticks Olfactory Test [Срок оценки: pre-intervention and at 1 and 3 months (may extend to 6 and 12 months) post-intervention]

Вторичные конечные точки (9)

• Procedure-related pain evaluation [Срок оценки: during the procedure and up to 2 weeks post-intervention]
• Retronasal Olfactory Test [Срок оценки: pre-intervention and at 3 months post-intervention]
• Visual Analogus Scale for olfaction [Срок оценки: pre-intervention and at 1 and 3 months (may extend to 6 and 12 months) post-intervention]
• Questionnaire of Olfactory Disorders (QOD) [Срок оценки: pre-intervention and at 1 and 3 months (may extend to 6 and 12 months) post-intervention]
• Beck Depression Inventory (BDI) [Срок оценки: pre-intervention and 3 months post-intervention]
• Montreal Cognitive Assessment (MoCA) [Срок оценки: pre-intervention and post-3 month intervention]
• 22-item Sinonasal Outcome Test (SNOT-22) [Срок оценки: pre-intervention and at 1 and 3 months (may extend to 6 and 12 months) post-intervention]
• Parosmia Questionnaire (PQ) [Срок оценки: pre-intervention and at 1 and 3 months (may extend to 6 and 12 months) post-intervention]
• Sniffin' Sticks Parosmia Test [Срок оценки: pre-intervention and 3 months post-intervention]

Критерии участия

Критерии включения

• Aged between 18 and 80 years, regardless of sex
• Subjective complaint of olfactory dysfunction with confirmed hyposmia or anosmia based on standardized olfactory testing
• History of at least 3 months of prior olfactory training but with persistent olfactory complaints

Критерии исключения

• Congenital anosmia
• Diagnosed neurological or structural brain abnormalities (e.g., brain tumor, major head trauma, stroke) with low likelihood of olfactory recovery
• Inability or unwillingness to comply with study procedures or follow-up assessments

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

Двойное слепое

Основная цель

Лечение

Центры проведения

Тайвань · 1 центр

• Taipei Veterans General Hospital — Taipei

Публикации

• Bae AY, Kim DH, Hwang SH. Efficacy of Platelet-Rich Plasma in the Treatment of Persistent Olfactory Impairment After COVID-19: A Systematic Review and Meta-Analysis. J Rhinol. 2024 Mar;31(1):1-7. doi: 10.18787/jr.2024.00006. Epub 2024 Mar 31. PMID 39664044
• Duffy A, Naimi B, Garvey E, Hunter S, Kumar A, Kahn C, Farquhar D, D'Souza G, Rawson N, Dalton P, Toskala E, Rabinowitz M, Rosen M, Nyquist G, Rosen D. Topical platelet-rich plasma as a possible treatment for olfactory dysfunction-A randomized controlled trial. Int Forum Allergy Rhinol. 2024 Sep;14(9):1455-1464. doi: 10.1002/alr.23363. Epub 2024 May 9. PMID 38722276
• Jiang RS, Chiang YF. The Effect of Platelet-Rich Plasma and Hyaluronic Acid Nasal Injections in the Treatment of Traumatic Olfactory Dysfunction. Ear Nose Throat J. 2024 Oct 15:1455613241291710. doi: 10.1177/01455613241291710. Online ahead of print. PMID 39404838
• Lechien JR, Le Bon SD, Saussez S. Platelet-rich plasma injection in the olfactory clefts of COVID-19 patients with long-term olfactory dysfunction. Eur Arch Otorhinolaryngol. 2023 May;280(5):2351-2358. doi: 10.1007/s00405-022-07788-8. Epub 2022 Dec 15. PMID 36520209
• Yan CH, Mundy DC, Patel ZM. The use of platelet-rich plasma in treatment of olfactory dysfunction: A pilot study. Laryngoscope Investig Otolaryngol. 2020 Feb 21;5(2):187-193. doi: 10.1002/lio2.357. eCollection 2020 Apr. PMID 32337347

Идентификаторы

NCT: NCT07151703 · 2025-06-010C · after funding being approved

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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