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

August 25, 2025 updated by: Yun-Ting Chao, Taipei Veterans General Hospital, Taiwan

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Dr. Yun-Ting Chao Principal Investigator (Attending Physician and Head of Dep.), PhD
  • Phone Number: 122 886-2-2875-7337
  • Email: yunting001@gmail.com

Study Locations

  • Taiwan
      • Taipei, Taiwan, 112201
        • Taipei Veterans General Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intranasal PRP injection
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.
Procedure: 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.
Combination product: 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 plasma (PRP). The centrifugation and PRP collection process takes about 5 minutes. Compared with traditional methods requiring manual identification and collection, this approach enhances the precision and safety of centrifugation-based preparation.
Device: 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 diary after every session.
Experimental: Topical PRP application arm
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.
Combination product: 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 plasma (PRP). The centrifugation and PRP collection process takes about 5 minutes. Compared with traditional methods requiring manual identification and collection, this approach enhances the precision and safety of centrifugation-based preparation.
Device: 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 diary after every session.
Procedure: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sniffin' Sticks Olfactory Test
Time Frame: 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.
pre-intervention and at 1 and 3 months (may extend to 6 and 12 months) post-intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Procedure-related pain evaluation
Time Frame: during the procedure and up to 2 weeks post-intervention
Visual analogue scale for pain (0-10) immediately after procedure.
during the procedure and up to 2 weeks post-intervention
Retronasal Olfactory Test
Time Frame: 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.
pre-intervention and at 3 months post-intervention
Visual Analogus Scale for olfaction
Time Frame: 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)
pre-intervention and at 1 and 3 months (may extend to 6 and 12 months) post-intervention
Questionnaire of Olfactory Disorders (QOD)
Time Frame: 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
pre-intervention and at 1 and 3 months (may extend to 6 and 12 months) post-intervention
Beck Depression Inventory (BDI)
Time Frame: 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.
pre-intervention and 3 months post-intervention
Montreal Cognitive Assessment (MoCA)
Time Frame: 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.
pre-intervention and post-3 month intervention
22-item Sinonasal Outcome Test (SNOT-22)
Time Frame: 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
pre-intervention and at 1 and 3 months (may extend to 6 and 12 months) post-intervention
Parosmia Questionnaire (PQ)
Time Frame: 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).
pre-intervention and at 1 and 3 months (may extend to 6 and 12 months) post-intervention
Sniffin' Sticks Parosmia Test
Time Frame: 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.
pre-intervention and 3 months post-intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Taipei Veterans General Hospital, Taiwan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2025

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

August 16, 2025

First Submitted That Met QC Criteria

August 25, 2025

First Posted (Estimated)

September 3, 2025

Study Record Updates

Last Update Posted (Estimated)

September 3, 2025

Last Update Submitted That Met QC Criteria

August 25, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-06-010C
  • after funding being approved (Other Grant/Funding Number: Taipei Veterans General Hospital)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

The decision regarding IPD sharing will be made upon completion of the study, pending institutional policies and ethical review board recommendations.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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