<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/NCT03773705</url>
  </required_header>
  <id_info>
    <org_study_id>17-301</org_study_id>
    <nct_id>NCT03773705</nct_id>
  </id_info>
  <brief_title>Impact of Nasoseptal Flap Harvest Technique on Olfaction Following Endoscopic Transsphenoidal Pituitary Surgery</brief_title>
  <official_title>Impact of Nasoseptal Flap Harvest Technique on Olfaction Following Endoscopic Transsphenoidal Pituitary Surgery: A Single-blinded Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Unity Health Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Unity Health Toronto</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>
      Pituitary tumours have an estimated prevalence of 20% in the general population and the&#xD;
      number of clinically relevant pituitary adenomas is increasing with time. When symptomatic,&#xD;
      the standard of care required for pituitary adenomas is resection through an endoscopic&#xD;
      transsphenoidal approach. There is however significant olfactory dysfunction following&#xD;
      endoscopic transsphenoidal pituitary surgery with approximately 23% of patients reporting&#xD;
      some degree of worsening in their sense of smell in the postoperative period.&#xD;
&#xD;
      Pedicled nasoseptal flaps are used to repair skull base defects following resection of skull&#xD;
      base tumours. The superior incision is placed in close proximity to olfactory mucosa.&#xD;
      Currently, these flaps are raised either with the use of electrocautery or scalpel. The use&#xD;
      of electrocautery in surgery has provided surgeons with greater hemostasis when compared to a&#xD;
      scalpel. This is of utmost importance in many regions of the head &amp; neck where highly&#xD;
      vascularized tissue results in difficulties achieving adequate hemostasis and therefore&#xD;
      limiting view of the surgical field. However, the use of electrocautery increases thermal&#xD;
      damage to surrounding tissue and impairs wound healing when compared to a scalpel.&#xD;
&#xD;
      Although the transmission of thermal energy via electrocautery to adjacent mucosa containing&#xD;
      olfactory epithelium may theoretically contribute to olfactory disturbances, no prospective&#xD;
      randomized controlled trials have yet examined the impact of these two different techniques&#xD;
      on postoperative olfactory function. The purpose of this research study is to determine the&#xD;
      effects, if any, of electrocautery versus scalpel on olfaction in raising the nasoseptal flap&#xD;
      for repairing skull base defects following transphenoidal surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pedicled nasoseptal flaps are used to repair skull base defects following endoscopic&#xD;
      transphenoidal surgery. The superior incision is placed in close proximity to olfactory&#xD;
      mucosa. Currently, these flaps are raised either with the use of electrocautery or scalpel.&#xD;
      While it is hypothesized that the olfactory mucosa is at greater risk of thermal injury with&#xD;
      the use of electrocautery, no prospective multi-center studies have examined the impact of&#xD;
      these two different techniques on postoperative olfactory function.&#xD;
&#xD;
      Patients will be recruited through the Otolaryngology-Head &amp; Neck Surgery clinics. Based on&#xD;
      previous studies in a North American population, a 10% change in UPSIT score was considered&#xD;
      to be significant. With an alpha error set to 0.05, a beta of 0.8 and an effect size of 1&#xD;
      standard deviation, a sample size of 20 was calculated.&#xD;
&#xD;
      After obtaining consent for enrolment into the study, each patient will undergo either: (1)&#xD;
      electrocautery or (2) scalpel in the elevation of nasoseptal flaps based on primary surgeon&#xD;
      preference. The University of Pennsylvania Smell Identification Test (UPSIT) will be used for&#xD;
      baseline testing of olfactory function in all enrolled patients. Postoperatively, all&#xD;
      enrolled patients will be seen in follow-up at 1, 3 and 6 months' time, at which point the&#xD;
      UPSIT will be administered for testing of postoperative olfactory function.&#xD;
&#xD;
      The Wilcoxon signed-rank test will be used to determine differences between UPSIT scores pre-&#xD;
      and postoperatively. Results of p&lt;0.05 will be considered statistically significant. Linear&#xD;
      regression will be used to examine relationships between UPSIT scores and other variables&#xD;
      collected (e.g., demographic data, size/type of pituitary tumour, length of nasoseptal flap).&#xD;
&#xD;
      Given that approximately 23% of all patients who undergo endoscopic transphenoidal surgery&#xD;
      note some degree of worsening in their sense of smell following surgery, a prospective&#xD;
      multi-center study comparing the two techniques would provide impetus to pursue one strategy&#xD;
      over another in order to maintain an important sense, olfaction. Through optimizing&#xD;
      preservation of olfactory mucosa during endoscopic skull base surgeries, patients' likelihood&#xD;
      of not detecting environmental hazards (e.g., smoke, gas, other poisonous materials) will be&#xD;
      reduced and, equally as important, their quality of life would be improved.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 25, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2019</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in University of Pennsylvania Smell Identification Test (UPSIT)</measure>
    <time_frame>Initial visit and at 1, 3 and 6-month follow-up visits</time_frame>
    <description>Standardized and validated test of olfaction, which uses microencapsulated odorants released by scratching test booklets. Participants are asked to fill out forced choice multiple alternative questionnaires regarding each odorant. Minimum total score 0, maximum total score 40. Higher scores represent a better outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Sniffin' Sticks</measure>
    <time_frame>Initial visit and at 1, 3 and 6-month follow-up visits</time_frame>
    <description>Validated 16-item odor identification test. Minimum total score 0, maximum total score 16. Higher scores represent better outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Sino-Nasal Outcome Test-22 (SNOT-22)</measure>
    <time_frame>Initial visit and at 1, 3 and 6-month follow-up visits</time_frame>
    <description>Disease-specific, quality-of-life related measure of sinonasal function. Test consists of 22 symptoms requiring responders to rate severity on a 5-point Likert scale 0-5. Minimum score 0, maximum score 110. Higher scores correlate with greater rhinosinusitus-related health burden.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Skull Base Inventory (SBI)</measure>
    <time_frame>Initial visit and at 1, 3 and 6-month follow-up visits</time_frame>
    <description>Multidimensional, disease-specific instrument designed to measure quality of life of patients who undergo surgical treatment for anterior or central skull base pathologies. It covers several disease-specific domains including cognitive, endocrine, nasal, neurologic, visual, and other general areas.Each item is weighted equally in each domain score. Each domain is weighted equally in the overall score. Domain scores are calculated by taking the total score (sum of all items) in that domain divided by the maximum possible score for that domain multiplied by 100. The minimum score for each domain is 0 and the maximum is 100. The minimum score for the questionnaire is 0 and the maximum is 100. Higher score indicates better outcomes.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Pre-Op and Post-Op Endoscopy Scores</measure>
    <time_frame>Initial visit and at 1, 3 and 6-month follow-up visits</time_frame>
    <description>Used to quantify the pathological states of the nose and paranasal sinuses. Calculated on left and right side out, minimum 0, maximum 14. Higher scores indicate objectively worse sinonasal inflammation.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Pituitary Tumor</condition>
  <condition>Surgery</condition>
  <condition>Olfactory Nerve Injuries</condition>
  <arm_group>
    <arm_group_label>Electrocautery group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Electrocautery used to raise pediclued nasoseptal flaps to repair skull based defects following endoscopic transphenoidal surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Scalpel group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Scalpel used to raise pediclued nasoseptal flaps to repair skull based defects following endoscopic transphenoidal surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Electrocautery versus scalpel</intervention_name>
    <description>Electrocautery versus scalpel in the elevation of nasoseptal flaps following endoscopic transsphenoidal pituitary surgery</description>
    <arm_group_label>Electrocautery group</arm_group_label>
    <arm_group_label>Scalpel group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients (age ≥18 years)&#xD;
&#xD;
          -  Patients with tumours of the pituitary gland electively scheduled for endoscopic&#xD;
             transsphenoidal surgery with nasoseptal flap coverage&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Documented evidence of sinonasal disease on either nasal endoscopy or radiography&#xD;
&#xD;
          -  Patients with a clinical history of asthma and/or sinonasal disease&#xD;
&#xD;
          -  Previous sinus surgery&#xD;
&#xD;
          -  Previous skull base surgery&#xD;
&#xD;
          -  History of pre-existing hyposmia or anosmia&#xD;
&#xD;
          -  Use of medication(s) known to alter sense of smell at time of test&#xD;
&#xD;
          -  UPSIT scores &lt;5 indicating a functional component to alteration in olfaction&#xD;
&#xD;
          -  Development of postoperative cerebrospinal fluid leak necessitating re-entry into the&#xD;
             operative field containing the nasoseptal flap&#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>John Lee, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Unity Health Toronto</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>John Lee, MD</last_name>
    <phone>416-864-5306</phone>
    <email>leejo@smh.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>St. Michael's Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5B 1W8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrea Figol, MSc</last_name>
      <phone>416-864-6060</phone>
      <phone_ext>6591</phone_ext>
      <email>FigolA@smh.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>August 19, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>March 13, 2019</last_update_submitted>
  <last_update_submitted_qc>March 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Unity Health Toronto</investigator_affiliation>
    <investigator_full_name>John Lee</investigator_full_name>
    <investigator_title>Head, Division of Rhinology, Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pituitary Neoplasms</mesh_term>
    <mesh_term>Pituitary Diseases</mesh_term>
    <mesh_term>Olfactory Nerve Injuries</mesh_term>
  </condition_browse>
  <!-- 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/NCT03773705
org study id: 17-301
nct id: NCT03773705
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Pituitary tumours have an estimated prevalence of 20% in the general population and the
      number of clinically relevant pituitary adenomas is increasing with time. When symptomatic,
      the standard of care required for pituitary adenomas is resection through an endoscopic
      transsphenoidal approach. There is however significant olfactory dysfunction following
      endoscopic transsphenoidal pituitary surgery with approximately 23% of patients reporting
      some degree of worsening in their sense of smell in the postoperative period.

      Pedicled nasoseptal flaps are used to repair skull base defects following resection of skull
      base tumours. The superior incision is placed in close proximity to olfactory mucosa.
      Currently, these flaps are raised either with the use of electrocautery or scalpel. The use
      of electrocautery in surgery has provided surgeons with greater hemostasis when compared to a
      scalpel. This is of utmost importance in many regions of the head & neck where highly
      vascularized tissue results in difficulties achieving adequate hemostasis and therefore
      limiting view of the surgical field. However, the use of electrocautery increases thermal
      damage to surrounding tissue and impairs wound healing when compared to a scalpel.

      Although the transmission of thermal energy via electrocautery to adjacent mucosa containing
      olfactory epithelium may theoretically contribute to olfactory disturbances, no prospective
      randomized controlled trials have yet examined the impact of these two different techniques
      on postoperative olfactory function. The purpose of this research study is to determine the
      effects, if any, of electrocautery versus scalpel on olfaction in raising the nasoseptal flap
      for repairing skull base defects following transphenoidal surgery.
Pedicled nasoseptal flaps are used to repair skull base defects following endoscopic
      transphenoidal surgery. The superior incision is placed in close proximity to olfactory
      mucosa. Currently, these flaps are raised either with the use of electrocautery or scalpel.
      While it is hypothesized that the olfactory mucosa is at greater risk of thermal injury with
      the use of electrocautery, no prospective multi-center studies have examined the impact of
      these two different techniques on postoperative olfactory function.

      Patients will be recruited through the Otolaryngology-Head & Neck Surgery clinics. Based on
      previous studies in a North American population, a 10% change in UPSIT score was considered
      to be significant. With an alpha error set to 0.05, a beta of 0.8 and an effect size of 1
      standard deviation, a sample size of 20 was calculated.

      After obtaining consent for enrolment into the study, each patient will undergo either: (1)
      electrocautery or (2) scalpel in the elevation of nasoseptal flaps based on primary surgeon
      preference. The University of Pennsylvania Smell Identification Test (UPSIT) will be used for
      baseline testing of olfactory function in all enrolled patients. Postoperatively, all
      enrolled patients will be seen in follow-up at 1, 3 and 6 months' time, at which point the
      UPSIT will be administered for testing of postoperative olfactory function.

      The Wilcoxon signed-rank test will be used to determine differences between UPSIT scores pre-
      and postoperatively. Results of p<0.05 will be considered statistically significant. Linear
      regression will be used to examine relationships between UPSIT scores and other variables
      collected (e.g., demographic data, size/type of pituitary tumour, length of nasoseptal flap).

      Given that approximately 23% of all patients who undergo endoscopic transphenoidal surgery
      note some degree of worsening in their sense of smell following surgery, a prospective
      multi-center study comparing the two techniques would provide impetus to pursue one strategy
      over another in order to maintain an important sense, olfaction. Through optimizing
      preservation of olfactory mucosa during endoscopic skull base surgeries, patients' likelihood
      of not detecting environmental hazards (e.g., smoke, gas, other poisonous materials) will be
      reduced and, equally as important, their quality of life would be improved.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Change in University of Pennsylvania Smell Identification Test (UPSIT)
time frame: Initial visit and at 1, 3 and 6-month follow-up visits
description: Standardized and validated test of olfaction, which uses microencapsulated odorants released by scratching test booklets. Participants are asked to fill out forced choice multiple alternative questionnaires regarding each odorant. Minimum total score 0, maximum total score 40. Higher scores represent a better outcome.
measure: Change in Sniffin' Sticks
time frame: Initial visit and at 1, 3 and 6-month follow-up visits
description: Validated 16-item odor identification test. Minimum total score 0, maximum total score 16. Higher scores represent better outcome.
measure: Change in Sino-Nasal Outcome Test-22 (SNOT-22)
time frame: Initial visit and at 1, 3 and 6-month follow-up visits
description: Disease-specific, quality-of-life related measure of sinonasal function. Test consists of 22 symptoms requiring responders to rate severity on a 5-point Likert scale 0-5. Minimum score 0, maximum score 110. Higher scores correlate with greater rhinosinusitus-related health burden.
measure: Change in Skull Base Inventory (SBI)
time frame: Initial visit and at 1, 3 and 6-month follow-up visits
description: Multidimensional, disease-specific instrument designed to measure quality of life of patients who undergo surgical treatment for anterior or central skull base pathologies. It covers several disease-specific domains including cognitive, endocrine, nasal, neurologic, visual, and other general areas.Each item is weighted equally in each domain score. Each domain is weighted equally in the overall score. Domain scores are calculated by taking the total score (sum of all items) in that domain divided by the maximum possible score for that domain multiplied by 100. The minimum score for each domain is 0 and the maximum is 100. The minimum score for the questionnaire is 0 and the maximum is 100. Higher score indicates better outcomes.
measure: Change in Pre-Op and Post-Op Endoscopy Scores
time frame: Initial visit and at 1, 3 and 6-month follow-up visits
description: Used to quantify the pathological states of the nose and paranasal sinuses. Calculated on left and right side out, minimum 0, maximum 14. Higher scores indicate objectively worse sinonasal inflammation.
arm group label: Electrocautery group
arm group type: Active Comparator
description: Electrocautery used to raise pediclued nasoseptal flaps to repair skull based defects following endoscopic transphenoidal surgery.
arm group label: Scalpel group
arm group type: Active Comparator
description: Scalpel used to raise pediclued nasoseptal flaps to repair skull based defects following endoscopic transphenoidal surgery.
intervention type: Procedure
intervention name: Electrocautery versus scalpel
description: Electrocautery versus scalpel in the elevation of nasoseptal flaps following endoscopic transsphenoidal pituitary surgery
arm group label: Electrocautery group
arm group label: Scalpel group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: John Lee, MD
role: Principal Investigator
affiliation: Unity Health Toronto
last name: John Lee, MD
phone: 416-864-5306
email: leejo@smh.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Unity Health Toronto
investigator full name: John Lee
investigator title: Head, Division of Rhinology, Principal Investigator
mesh term: Pituitary Neoplasms
mesh term: Pituitary Diseases
mesh term: Olfactory Nerve Injuries