<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04406584</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-55353</org_study_id>
    <nct_id>NCT04406584</nct_id>
  </id_info>
  <brief_title>Intranasal Injection of PRP Versus Saline for Treatment of Olfactory Dysfunction</brief_title>
  <official_title>Intranasal Injection of Platelet-rich Plasma Versus Saline for Treatment of Olfactory Dysfunction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized clinical trial will evaluate the benefit of platelet-rich plasma (PrP) in the&#xD;
      treatment of olfactory dysfunction. PrP can be isolated from a patient's own blood and has&#xD;
      been found in previous studies to have anti-inflammatory and pro-regenerative properties. It&#xD;
      has been used across multiple specialties, such as Orthopedics, Facial Plastics, Dermatology,&#xD;
      Neurology in injected form to treat a wide variety of tissues to encourage the body's&#xD;
      inherent regenerative capacity. The investigators have completed a pilot study here&#xD;
      evaluating it's use in olfactory loss which demonstrated safety and also suggested efficacy.&#xD;
      Therefore, the investigators aim to assess the ability of PrP to improve olfactory function&#xD;
      in patients with decreased sense of smell.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Olfactory dysfunction constitutes a common impairment in the general population, affecting&#xD;
      nearly 20 million in the USA and severely impairing quality of life. Unfortunately, this&#xD;
      problem is often permanent, and no effective treatment is available at this time. Although&#xD;
      many etiologies exist for olfactory loss, the underlying pathology is thought to be permanent&#xD;
      damage to the olfactory bulb, nerves or basal cells of the olfactory system. Platelet-rich&#xD;
      plasma (PRP) is an autologous treatment derived from a patient's own blood and has been found&#xD;
      to have pro-nerve regenerative properties in animal and human studies. A small pilot study at&#xD;
      the principal investigator's institution demonstrated improved olfactory thresholds in&#xD;
      patients with partial olfactory loss who received PrP injections. In this randomized clinical&#xD;
      trial, the investigators aim to further evaluate the ability of PRP injections to restore&#xD;
      olfactory function in human subjects. Given the lack of effective current treatments, a&#xD;
      therapeutic benefit of PrP would represent a crucial advancement in research and treatment of&#xD;
      olfactory loss, which affects a large swath of the population.&#xD;
&#xD;
      Patients will be seen at the Stanford Sinus center, or at the newly added collaborating&#xD;
      institution UCSD, and those with smell loss will be identified by the clinically validated&#xD;
      patient directed survey: The UPSIT (University of Pennsylvania Smell Identification Test).&#xD;
      They will undergo nasal endoscopy to exclude structural causes of smell loss including mass&#xD;
      or tumor. Nasal endoscopy will be performed to exclude structural causes of olfactory, using&#xD;
      topical anesthesia (1% phenylephrine &amp; 4% lidocaine topical spray). THESE ABOVE STEPS&#xD;
      CONSTITUTE STANDARD OF CARE FOR EVALUATION OF OLFACTORY LOSS.&#xD;
&#xD;
      The timing of the initial research visit will depend on the evolution of the current covid-19&#xD;
      pandemic and adhere to Stanford guidelines regarding research visits. At the initial research&#xD;
      visit, patients meeting inclusion criteria will be evaluated in a procedure room at the&#xD;
      Stanford Sinus center. A baseline Sniffin' sticks smell test will be performed (see below). A&#xD;
      small vial of blood will be drawn from the patient at the Blake Wilbur first floor&#xD;
      laboratory. The research coordinator will walk the patient back to clinic along with the&#xD;
      patient's blood smple. PRP will be isolated from the blood by the study investigator,&#xD;
      following manufacturer instructions from the PurePRP preparation kit (Emcyte corporation),&#xD;
      which will involve use of a centrifuge located in the clinic for this purpose. 0.5 mL of the&#xD;
      PRP solution will be set aside for platelet quantification. From the remaining PRP solution,&#xD;
      patients will then receive 1ml of autologous PrP or sterile saline (0.9% Sodium Chloride),&#xD;
      which will be injected into the superior septum mucosa near the olfactory groove bilaterally.&#xD;
      Patients will be blindfolded during injection to prevent identification of the injected&#xD;
      specimen, and will previously be randomized in a 1:1 ratio via a random number generator.&#xD;
      Patients will be monitored for side effects for 15 minutes. (We routinely perform nasal&#xD;
      endoscopy with injection and associated procedures in our clinic, which patients tolerate&#xD;
      very well.) Injections will then be performed twice more at 2-weeks and 4-weeks after the&#xD;
      initial injection, for a total of 3 biweekly injections. ALL OF THE ABOVE STEPS ARE FOR&#xD;
      RESEARCH PURPOSES.&#xD;
&#xD;
      The Sniffin' Sticks test is a validated, non-invasive assessment of olfactory function via&#xD;
      presentation of scented felt pens to blindfolded patients. The output is the TDI score&#xD;
      (threshold, discrimination, identification). The TDI score will be recorded at baseline&#xD;
      (initial research visit), and then at 1-month and 3-months after the initial test, for a&#xD;
      total of 3 tests. The first test will occur before the first injection, and the second test&#xD;
      will be performed before the third injection. There will be no injection at the last (third)&#xD;
      test. THE ABOVE VISITS ARE FOR RESEARCH PURPOSES.&#xD;
&#xD;
      The study time-line is summarized as follows Visit 1: 1st Sniffin' Sticks test, 1st injection&#xD;
      Visit 2: 2 weeks after Visit 1, second injection Visit 3: 4 weeks after Visit 1, second test,&#xD;
      third injection Visit 4: 3 months after Visit 1, third test&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 22, 2021</start_date>
  <completion_date type="Actual">August 11, 2022</completion_date>
  <primary_completion_date type="Actual">May 12, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Comparison of two randomized groups</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Blindfold during injection and during portions of the smell test</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Smelling ability</measure>
    <time_frame>6 months</time_frame>
    <description>Using Sniffin' Sticks olfactory testing pens to test smell</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Olfactory Disorder</condition>
  <condition>Olfaction Disorders</condition>
  <condition>Olfactory Nerve Injuries</condition>
  <condition>Olfactory Nerve Disorder</condition>
  <condition>Olfactory Nerve Diseases</condition>
  <condition>Covid19</condition>
  <condition>Post-Viral Disorder</condition>
  <arm_group>
    <arm_group_label>Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Injection of 1cc saline into olfactory cleft x4</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Platelet Rich Plasma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Injection of 1cc patient's own platelet rich plasma (PRP) into olfactory cleft x4</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Injection into olfactory cleft</intervention_name>
    <description>Already stated above.</description>
    <arm_group_label>Platelet Rich Plasma</arm_group_label>
    <arm_group_label>Saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients &gt;= 18 years of age&#xD;
&#xD;
          -  Patients who have olfactory loss (based off of UPSIT score &lt;= 33 out of 40)&#xD;
&#xD;
          -  Patients who also have an age-adjusted TDI Sniffin' Sticks score that demonstrates&#xD;
             hyposmia (TDI&gt;16 and &lt;30)&#xD;
&#xD;
          -  Etiology of olfactory loss is due to URI or idiopathic&#xD;
&#xD;
          -  At least 6 months of olfactory loss but less than 12 months&#xD;
&#xD;
          -  Patients can have been previously treated with oral and topical steroids but this is&#xD;
             not a requirement&#xD;
&#xD;
          -  Patients will receive concurrent olfactory training - the practice of smelling strong&#xD;
             odors (standard of care)&#xD;
&#xD;
          -  Be able to read and understand English&#xD;
&#xD;
          -  Agree to participate in the study&#xD;
&#xD;
          -  Be able and willing to provide Informed Consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients &lt; 18 years of age&#xD;
&#xD;
          -  Pregnant females&#xD;
&#xD;
          -  Patient who have any structural abnormalities on nasal endoscopy or radiographic&#xD;
             imaging&#xD;
&#xD;
          -  Olfactory loss due to trauma, chronic sinusitis / inflammation / polyps, neoplasms, or&#xD;
             neurodegenerative diseases&#xD;
&#xD;
          -  Patients who have had olfactory loss &gt; 12 months&#xD;
&#xD;
          -  Patients with bleeding disorders or on blood thinners such as coumadin and plavix&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zara M. Patel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California - San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://profiles.stanford.edu/zara-patel</url>
    <description>Dr. Patel's Stanford University School of Medicine Profile and Link to Donate to Research</description>
  </link>
  <reference>
    <citation>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.</citation>
    <PMID>32337347</PMID>
  </reference>
  <results_reference>
    <citation>Yan CH, Jang SS, Lin HC, Ma Y, Khanwalkar AR, Thai A, Patel ZM. Use of platelet-rich plasma for COVID-19-related olfactory loss: a randomized controlled trial. Int Forum Allergy Rhinol. 2023 Jun;13(6):989-997. doi: 10.1002/alr.23116. Epub 2022 Dec 21.</citation>
    <PMID>36507615</PMID>
  </results_reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>May 11, 2020</study_first_submitted>
  <study_first_submitted_qc>May 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>March 9, 2023</last_update_submitted>
  <last_update_submitted_qc>March 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Zara M. Patel</investigator_full_name>
    <investigator_title>Professor and Director of Endoscopic Skull Base Surgery</investigator_title>
  </responsible_party>
  <keyword>olfactory</keyword>
  <keyword>olfactory loss</keyword>
  <keyword>anosmia</keyword>
  <keyword>hyposmia</keyword>
  <keyword>olfactory dysfunction</keyword>
  <keyword>prp</keyword>
  <keyword>platelet enriched plasma</keyword>
  <keyword>platelet rich plasma</keyword>
  <keyword>endoscopic</keyword>
  <keyword>covid19</keyword>
  <keyword>post-viral disorder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Nervous System Diseases</mesh_term>
    <mesh_term>Olfaction Disorders</mesh_term>
    <mesh_term>Olfactory Nerve Injuries</mesh_term>
    <mesh_term>Olfactory Nerve Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04406584
org study id: IRB-55353
nct id: NCT04406584
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This randomized clinical trial will evaluate the benefit of platelet-rich plasma (PrP) in the
      treatment of olfactory dysfunction. PrP can be isolated from a patient's own blood and has
      been found in previous studies to have anti-inflammatory and pro-regenerative properties. It
      has been used across multiple specialties, such as Orthopedics, Facial Plastics, Dermatology,
      Neurology in injected form to treat a wide variety of tissues to encourage the body's
      inherent regenerative capacity. The investigators have completed a pilot study here
      evaluating it's use in olfactory loss which demonstrated safety and also suggested efficacy.
      Therefore, the investigators aim to assess the ability of PrP to improve olfactory function
      in patients with decreased sense of smell.
Olfactory dysfunction constitutes a common impairment in the general population, affecting
      nearly 20 million in the USA and severely impairing quality of life. Unfortunately, this
      problem is often permanent, and no effective treatment is available at this time. Although
      many etiologies exist for olfactory loss, the underlying pathology is thought to be permanent
      damage to the olfactory bulb, nerves or basal cells of the olfactory system. Platelet-rich
      plasma (PRP) is an autologous treatment derived from a patient's own blood and has been found
      to have pro-nerve regenerative properties in animal and human studies. A small pilot study at
      the principal investigator's institution demonstrated improved olfactory thresholds in
      patients with partial olfactory loss who received PrP injections. In this randomized clinical
      trial, the investigators aim to further evaluate the ability of PRP injections to restore
      olfactory function in human subjects. Given the lack of effective current treatments, a
      therapeutic benefit of PrP would represent a crucial advancement in research and treatment of
      olfactory loss, which affects a large swath of the population.

      Patients will be seen at the Stanford Sinus center, or at the newly added collaborating
      institution UCSD, and those with smell loss will be identified by the clinically validated
      patient directed survey: The UPSIT (University of Pennsylvania Smell Identification Test).
      They will undergo nasal endoscopy to exclude structural causes of smell loss including mass
      or tumor. Nasal endoscopy will be performed to exclude structural causes of olfactory, using
      topical anesthesia (1% phenylephrine & 4% lidocaine topical spray). THESE ABOVE STEPS
      CONSTITUTE STANDARD OF CARE FOR EVALUATION OF OLFACTORY LOSS.

      The timing of the initial research visit will depend on the evolution of the current covid-19
      pandemic and adhere to Stanford guidelines regarding research visits. At the initial research
      visit, patients meeting inclusion criteria will be evaluated in a procedure room at the
      Stanford Sinus center. A baseline Sniffin' sticks smell test will be performed (see below). A
      small vial of blood will be drawn from the patient at the Blake Wilbur first floor
      laboratory. The research coordinator will walk the patient back to clinic along with the
      patient's blood smple. PRP will be isolated from the blood by the study investigator,
      following manufacturer instructions from the PurePRP preparation kit (Emcyte corporation),
      which will involve use of a centrifuge located in the clinic for this purpose. 0.5 mL of the
      PRP solution will be set aside for platelet quantification. From the remaining PRP solution,
      patients will then receive 1ml of autologous PrP or sterile saline (0.9% Sodium Chloride),
      which will be injected into the superior septum mucosa near the olfactory groove bilaterally.
      Patients will be blindfolded during injection to prevent identification of the injected
      specimen, and will previously be randomized in a 1:1 ratio via a random number generator.
      Patients will be monitored for side effects for 15 minutes. (We routinely perform nasal
      endoscopy with injection and associated procedures in our clinic, which patients tolerate
      very well.) Injections will then be performed twice more at 2-weeks and 4-weeks after the
      initial injection, for a total of 3 biweekly injections. ALL OF THE ABOVE STEPS ARE FOR
      RESEARCH PURPOSES.

      The Sniffin' Sticks test is a validated, non-invasive assessment of olfactory function via
      presentation of scented felt pens to blindfolded patients. The output is the TDI score
      (threshold, discrimination, identification). The TDI score will be recorded at baseline
      (initial research visit), and then at 1-month and 3-months after the initial test, for a
      total of 3 tests. The first test will occur before the first injection, and the second test
      will be performed before the third injection. There will be no injection at the last (third)
      test. THE ABOVE VISITS ARE FOR RESEARCH PURPOSES.

      The study time-line is summarized as follows Visit 1: 1st Sniffin' Sticks test, 1st injection
      Visit 2: 2 weeks after Visit 1, second injection Visit 3: 4 weeks after Visit 1, second test,
      third injection Visit 4: 3 months after Visit 1, third test
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Comparison of two randomized groups
primary purpose: Treatment
masking: Single (Participant)
masking description: Blindfold during injection and during portions of the smell test
measure: Smelling ability
time frame: 6 months
description: Using Sniffin' Sticks olfactory testing pens to test smell
arm group label: Saline
arm group type: Placebo Comparator
description: Injection of 1cc saline into olfactory cleft x4
arm group label: Platelet Rich Plasma
arm group type: Experimental
description: Injection of 1cc patient's own platelet rich plasma (PRP) into olfactory cleft x4
intervention type: Procedure
intervention name: Injection into olfactory cleft
description: Already stated above.
arm group label: Platelet Rich Plasma
arm group label: Saline
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Zara M. Patel, MD
role: Principal Investigator
affiliation: Stanford University
facility: 
facility: 
country: United States
url: https://profiles.stanford.edu/zara-patel
description: Dr. Patel's Stanford University School of Medicine Profile and Link to Donate to Research
citation: 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
citation: Yan CH, Jang SS, Lin HC, Ma Y, Khanwalkar AR, Thai A, Patel ZM. Use of platelet-rich plasma for COVID-19-related olfactory loss: a randomized controlled trial. Int Forum Allergy Rhinol. 2023 Jun;13(6):989-997. doi: 10.1002/alr.23116. Epub 2022 Dec 21.
PMID: 36507615
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Zara M. Patel
investigator title: Professor and Director of Endoscopic Skull Base Surgery
mesh term: COVID-19
mesh term: Virus Diseases
mesh term: Nervous System Diseases
mesh term: Olfaction Disorders
mesh term: Olfactory Nerve Injuries
mesh term: Olfactory Nerve Diseases
sharing ipd: No