Topical Versus Injection PRP for Olfactory Dysfunction

Not Applicable

Not yet recruiting

• Conditions: Olfactory Dysfunction; Anosmia; Hyposmia

• Registration Number: NCT07151703
• Lead Sponsor: Taipei Veterans General Hospital, Taiwan

Brief Summary

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.

Detailed 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.

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-16
• Study First Submitted QC: 2025-08-25
• Last Update Submitted: 2025-08-25
• Study First Posted: 2025-09-03
• Last Update Posted: 2025-09-03
• Study Start: 2025-10-01
• Primary Completion: 2027-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Sniffin' Sticks Olfactory Test	pre-intervention and at 1 and 3 months (may extend to 6 and 12 months) post-intervention	The Sniffin' Sticks test (Burghart Messtechnik GmbH, Holm, Germany) comprises three subtests for odor detection threshold (T), odor discrimination (D), and odor identification (I). This test employs odor-containing felt-tip pens, which are presented to participants to evaluate their olfactory performance.; In the detection threshold subtest, we employed an adaptive staircase procedure based on a three-alternative forced-choice format. Participants were tasked with differentiating a stick with a rose-like aroma (phenylethyl alcohol) from two blank sticks. Odor discrimination was assessed using 16 pen triplets, two of which contained identical odors and one stick contained a different odor. Participants were tasked with identifying the odd one out. In the odor identification subtest, participants were tasked with naming 16 common odors by selecting appropriate terms from a set of four descriptors per odor. The scores from each subtest were combined into a composite TDI score.

Secondary Outcome Measures

Name	Time	Method
Procedure-related pain evaluation	during the procedure and up to 2 weeks post-intervention	Visual analogue scale for pain (0-10) immediately after procedure.
Retronasal Olfactory Test	pre-intervention and at 3 months post-intervention	Retronasal olfactory testing was performed using standardized odorized powders/capsules presented in the oral cavity, with participants instructed to exhale through the nose and rate the perceived odor. It specifically evaluates olfactory function via the retronasal route.
Visual Analogus Scale for olfaction	pre-intervention and at 1 and 3 months (may extend to 6 and 12 months) post-intervention	Visual Analogus Scale for olfactory function from 0 to 10. (0 means inability of smelling and 10 means super good smell function)
Questionnaire of Olfactory Disorders (QOD)	pre-intervention and at 1 and 3 months (may extend to 6 and 12 months) post-intervention	A questionnaire on olfaction-related quality of life status
Beck Depression Inventory (BDI)	pre-intervention and 3 months post-intervention	The Beck Depression Inventory (BDI) is a standardized self-report questionnaire measuring the severity of depressive symptoms. Olfactory loss, resulting from viral infections or other etiologies, has been associated with mood disturbances and reduced emotional well-being.
Montreal Cognitive Assessment (MoCA)	pre-intervention and post-3 month intervention	The Montreal Cognitive Assessment (MoCA) is a widely used screening tool for mild cognitive impairment. Olfactory loss has been shown to diminish sensory stimulation to the brain, potentially affecting neural processing and cognitive function.
22-item Sinonasal Outcome Test (SNOT-22)	pre-intervention and at 1 and 3 months (may extend to 6 and 12 months) post-intervention	A questionaire reflecting the severity of symptoms and the impact of sinonasal diseases
Parosmia Questionnaire (PQ)	pre-intervention and at 1 and 3 months (may extend to 6 and 12 months) post-intervention	A 4-item questionnaire to evaluate the presence, severity, and qualitative characteristics of odor distortions (parosmia).
Sniffin' Sticks Parosmia Test	pre-intervention and 3 months post-intervention	SSParoT (Sniffin' Sticks Parosmia Test) is a specialized assessment tool to evaluate qualitative olfactory function, particularly for the objective quantification of parosmia. It presents a series of well-characterized odorants and asks participants to rate each odor's pleasantness. From these ratings, the range of hedonic ratings and the hedonic orientation are calculated, providing quantitative measures of the breadth and direction of the participant's odor preference profile. This approach enables clinicians to identify patterns of altered odor perception and monitor changes following therapeutic interventions. The SSParoT (Sniffin' Sticks Parosmia Test) was additionally administered to participants with parosmia to calculate the range of hedonic ratings and the hedonic orientation.

Trial Locations

Locations (1)

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan