Topical Versus Injection PRP for Olfactory Dysfunction (TOP-IN)

Taipei Veterans General Hospital

Status and phase: Not yet enrolling; Phase 3

Conditions: Anosmia; Olfactory Dysfunction; Hyposmia

Treatments: Combination Product: platelet-rich plasma; Procedure: Carrier-Assisted Topical Application of Autologous PRP; Device: olfactory training; Procedure: Intranasal Injection of Autologous PRP

Study type: Interventional

Funder types: Other

Identifiers

NCT07151703

after funding being approved (Other Grant/Funding Number)

2025-06-010C

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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60 participants in 2 patient groups

Intranasal PRP injection

Experimental group

Description:

Participants in this arm will receive an intranasal injection of autologous platelet-rich plasma (PRP) into the olfactory cleft. The procedure will be conducted under local anesthesia using endoscopic guidance. All participants will also perform standardized daily olfactory training for three months following the intervention.

Treatment:

Procedure: Intranasal Injection of Autologous PRP

Device: olfactory training

Combination Product: platelet-rich plasma

Topical PRP application arm

Experimental group

Description:

Participants in this arm will receive a topical application of autologous PRP delivered via PRP-soaked absorbable material (Gelfoam) placed into the olfactory cleft. No needle will be used. The placement will be guided by nasal endoscopy under local anesthesia. Daily olfactory training will be continued for three months post-application.

Treatment:

Device: olfactory training

Combination Product: platelet-rich plasma

Procedure: Carrier-Assisted Topical Application of Autologous PRP