<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/NCT03283020</url>
  </required_header>
  <id_info>
    <org_study_id>JS006</org_study_id>
    <nct_id>NCT03283020</nct_id>
  </id_info>
  <brief_title>Opioid-Induced Swallowing Dysfunction - The Impact of Bolus Volume</brief_title>
  <official_title>Opioid-Induced Swallowing Dysfunction - The Impact of Bolus Volume: a Randomized, Double-Blind Study in Healthy Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Region Örebro County</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Region Örebro County</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The purpose of the study is to evaluate the impact of different bolus volumes and viscosity&#xD;
      on remifentanil-induced swallowing dysfunction in healthy volunteers.Hence, whether&#xD;
      swallowing tasks can be done safer during sedation by altering bolus volumes and viscosities&#xD;
      will be revealed. Furthermore, the study will clarify underlying mechanisms (central vs.&#xD;
      peripheral effects) of remifentanil-induced swallowing dysfunction. If methylnaltrexone&#xD;
      reverses the remifentanil-induced effects on swallowing, this would suggest a dominant&#xD;
      peripherally mediated mechanism.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Monitored anesthesia care (MAC) is commonly applied in modern perioperative care and means&#xD;
      that minor surgical procedures are accomplished in awake patients using local anesthesia and&#xD;
      light sedation. MAC has many advantages compared to general anesthesia; the recovery time&#xD;
      after anesthesia is shorter and risk for postoperative nausea is lower to mention some.&#xD;
      However, the patient is spontaneously breathing and the airway is not protected by an&#xD;
      endotracheal tube which potentially increases risk of pulmonary aspiration. Pulmonary&#xD;
      aspiration, that is inhalation of stomach and/or pharyngeal contents into the lungs, is a&#xD;
      severe anesthesia-related complication and can in worst case lead to pneumonia and even&#xD;
      death. Intact swallowing function is crucial in avoiding aspiration and how sedatives and&#xD;
      analgesic agents used during MAC influence swallowing function is not fully understood.&#xD;
&#xD;
      Pharyngeal function during bolus swallowing is measured by combined high resolution impedance&#xD;
      manometry (HRIM). The HRIM catheter is inserted through the nose in such a way that sensors&#xD;
      straddle the entire pharynx and esophagus with the distal catheter tip in the stomach.&#xD;
      Dynamic pressure changes and flow can be detected during swallowing and data registered by&#xD;
      HRIM are analysed using purpose-designed software, AIM analysis (automated impedance&#xD;
      manometry analysis). AIM analysis derives pressure flow variables which describe different&#xD;
      physiological events like bolus timing and bolus distension in the pharynx and the esophagus&#xD;
      during swallowing. A Swallow Risk Index value, quantifying risk of deglutitive aspiration,&#xD;
      can also be defined.&#xD;
&#xD;
      The aim of the study is to evaluate impact of different bolus volumes on remifentanil-induced&#xD;
      swallowing dysfunction in healthy volunteers. The study will clarify underlying mechanisms&#xD;
      (central vs. peripheral effects) of remifentanil-induced swallowing dysfunction. Furthermore,&#xD;
      whether swallowing tasks can be done safer during sedation by altering bolus volumes will be&#xD;
      revealed. In addition to bolus volume, different bolus viscosities will be tested. It is&#xD;
      shown that higher bolus viscosity diminishes misdirected swallows in dysphagic patients and&#xD;
      higher bolus viscosity may possibly counteracts the swallowing dysfunction induced by&#xD;
      remifentanil. Moreover, if MNTX reverses the remifentanil-induced effects on swallowing, then&#xD;
      this would suggest a dominant peripherally mediated mechanism. Our aim is also to evaluate&#xD;
      impact of remifentanil exposure on esophageal motility and impact of methylnaltrexone alone&#xD;
      on swallowing function.&#xD;
&#xD;
      20 healthy volunteers will be studied on two different occasions approximately one week&#xD;
      apart. In a randomized order volunteers will receive intravenous infusion of remifentanil and&#xD;
      an intravenous injection of MNTX on one occasion, and placebo (normal saline) infusion and an&#xD;
      intravenous injection of MNTX on the other occasion. Blood samples are obtained for plasma&#xD;
      concentration determination of the study drug and sedation levels are assessed during study&#xD;
      drug exposure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 11, 2017</start_date>
  <completion_date type="Anticipated">April 1, 2018</completion_date>
  <primary_completion_date type="Anticipated">April 1, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pressure Flow pharyngeal variables, 10 ml vs 20 ml bolus</measure>
    <time_frame>Up to 60 minutes</time_frame>
    <description>Difference in pharyngeal pressure flow variables during remifentanil exposure between bolus volumes of 10 ml and 20 ml compared to placebo.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pressure Flow pharyngeal variables, liquid vs semisolid bolus</measure>
    <time_frame>Up to 60 minutes</time_frame>
    <description>Difference in pharyngeal pressure flow variables during remifentanil exposure between liquid and semisolid boluses compared to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pressure Flow pharyngeal variables, remifentanil before vs after methylnaltrexone</measure>
    <time_frame>Up to 60 minutes</time_frame>
    <description>Difference in pharyngeal pressure flow variables during remifentanil exposure before and after methylnaltrexone administration compared to placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pressure Flow pharyngeal variables, placebo before vs after methylnaltrexone</measure>
    <time_frame>Up to 60 minutes</time_frame>
    <description>Difference in pharyngeal pressure flow variables during placebo infusion before and after methylnaltrexone administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pressure Flow esophageal motility variables, 10 ml vs 20 ml bolus</measure>
    <time_frame>Up to 60 minutes</time_frame>
    <description>Difference in variables of esophageal motility between different bolus volumes during remifentanil exposure compared to placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pressure Flow esophageal motility variables, liquid vs semisolid bolus</measure>
    <time_frame>Up to 60 minutes</time_frame>
    <description>Difference in variables of esophageal motility between liquid and semisolid boluses during remifentanil exposure compared to placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pressure Flow esophageal motility variables, remifentanil before vs after methylnaltrexone</measure>
    <time_frame>Up to 60 minutes</time_frame>
    <description>Difference in variables of esophageal motility during remifentanil exposure before and after methylnaltrexone administration compared to placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pressure Flow esophageal motility variables, placebo before vs after methylnaltrexone</measure>
    <time_frame>Up to 60 minutes</time_frame>
    <description>Difference in variables of esophageal motility during placebo infusion before and after methylnaltrexone administration.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Pharyngeal Dysfunction</condition>
  <condition>Pharyngeal Swallowing</condition>
  <arm_group>
    <arm_group_label>RemifentanilMNTX</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Volunteers are given an intravenous infusion with remifentanil, with an effect-site target concentration of 3 ng/ml via a target-controlled infusion (TCI) pump. After a series of swallowing tests an intravenous injection of methylnaltrexone of 0,3 mg/kg is given.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>PlaceboMNTX</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Volunteers are given an intravenous infusion with saline 0,9%. After a series of swallowing tests an intravenous injection of methylnaltrexone of 0,3 mg/kg is given.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RemifentanilMNTX</intervention_name>
    <description>Remifentanil infusion TCI 3 ng/ml, Methylnaltrexone injection 0.3 mg/kg</description>
    <arm_group_label>RemifentanilMNTX</arm_group_label>
    <other_name>Methylnaltrexone</other_name>
    <other_name>Remifentanil</other_name>
    <other_name>Relistor</other_name>
    <other_name>Ultiva</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PlaceboMNTX</intervention_name>
    <description>Placebo (NaCl 0.9%) TCI infusion, Methylnaltrexone injection 0.3 mg/kg</description>
    <arm_group_label>PlaceboMNTX</arm_group_label>
    <other_name>Sodium Chloride 0.9%</other_name>
    <other_name>Methylnaltrexone</other_name>
    <other_name>Relistor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. ≥ 18 - ≤ 40 year old healthy volunteers from both sexes.&#xD;
&#xD;
          2. Have signed and dated Informed Consent.&#xD;
&#xD;
          3. Willing and able to comply with the protocol for the duration of the trial.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Anamnesis of pharyngoesophageal dysfunction.&#xD;
&#xD;
          2. Known or history of gastrointestinal, severe cardiac, pulmonary or neurological&#xD;
             disease&#xD;
&#xD;
          3. Ongoing medication that may affect upper gastrointestinal tract, larynx or lower&#xD;
             airway.&#xD;
&#xD;
          4. Allergies to or history of reaction to remifentanil, fentanyl analogues or&#xD;
             dexmedetomidine.&#xD;
&#xD;
          5. Pregnancy or breast feeding&#xD;
&#xD;
          6. BMI &gt; 30&#xD;
&#xD;
          7. Smoking&#xD;
&#xD;
          8. Previous participation in a medicinal clinical trial during the last year where an&#xD;
             opioid has been used or have during the last 30 days participated in any other&#xD;
             medicinal clinical trial or in a trial where follow-up is not completed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Johanna Savilampi, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University hospital in Örebro</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Johanna Savilampi, MD, PhD</last_name>
    <phone>+46196020266</phone>
    <email>johanna.savilampi@regionorebrolan.se</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department of Anaesthesiology and Intensive Care, Örebro University Hospital</name>
      <address>
        <city>Örebro</city>
        <zip>70185</zip>
        <country>Sweden</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Johanna Savilampi, Phd</last_name>
      <email>johanna.savilampi@regionorebrolan.se</email>
    </contact>
    <contact_backup>
      <last_name>Per Cajander, MD</last_name>
      <email>per.cajander@regionorebrolan.se</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <last_update_submitted>December 11, 2017</last_update_submitted>
  <last_update_submitted_qc>December 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 12, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Region Örebro County</investigator_affiliation>
    <investigator_full_name>Johanna Savilampi</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Remifentanil</keyword>
  <keyword>Methylnaltrexone</keyword>
  <keyword>Pharyngeal dysfunction</keyword>
  <keyword>Anesthetic sedation</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Naltrexone</mesh_term>
    <mesh_term>Remifentanil</mesh_term>
    <mesh_term>Methylnaltrexone</mesh_term>
  </intervention_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/NCT03283020
org study id: JS006
nct id: NCT03283020
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of the study is to evaluate the impact of different bolus volumes and viscosity
      on remifentanil-induced swallowing dysfunction in healthy volunteers.Hence, whether
      swallowing tasks can be done safer during sedation by altering bolus volumes and viscosities
      will be revealed. Furthermore, the study will clarify underlying mechanisms (central vs.
      peripheral effects) of remifentanil-induced swallowing dysfunction. If methylnaltrexone
      reverses the remifentanil-induced effects on swallowing, this would suggest a dominant
      peripherally mediated mechanism.
Monitored anesthesia care (MAC) is commonly applied in modern perioperative care and means
      that minor surgical procedures are accomplished in awake patients using local anesthesia and
      light sedation. MAC has many advantages compared to general anesthesia; the recovery time
      after anesthesia is shorter and risk for postoperative nausea is lower to mention some.
      However, the patient is spontaneously breathing and the airway is not protected by an
      endotracheal tube which potentially increases risk of pulmonary aspiration. Pulmonary
      aspiration, that is inhalation of stomach and/or pharyngeal contents into the lungs, is a
      severe anesthesia-related complication and can in worst case lead to pneumonia and even
      death. Intact swallowing function is crucial in avoiding aspiration and how sedatives and
      analgesic agents used during MAC influence swallowing function is not fully understood.

      Pharyngeal function during bolus swallowing is measured by combined high resolution impedance
      manometry (HRIM). The HRIM catheter is inserted through the nose in such a way that sensors
      straddle the entire pharynx and esophagus with the distal catheter tip in the stomach.
      Dynamic pressure changes and flow can be detected during swallowing and data registered by
      HRIM are analysed using purpose-designed software, AIM analysis (automated impedance
      manometry analysis). AIM analysis derives pressure flow variables which describe different
      physiological events like bolus timing and bolus distension in the pharynx and the esophagus
      during swallowing. A Swallow Risk Index value, quantifying risk of deglutitive aspiration,
      can also be defined.

      The aim of the study is to evaluate impact of different bolus volumes on remifentanil-induced
      swallowing dysfunction in healthy volunteers. The study will clarify underlying mechanisms
      (central vs. peripheral effects) of remifentanil-induced swallowing dysfunction. Furthermore,
      whether swallowing tasks can be done safer during sedation by altering bolus volumes will be
      revealed. In addition to bolus volume, different bolus viscosities will be tested. It is
      shown that higher bolus viscosity diminishes misdirected swallows in dysphagic patients and
      higher bolus viscosity may possibly counteracts the swallowing dysfunction induced by
      remifentanil. Moreover, if MNTX reverses the remifentanil-induced effects on swallowing, then
      this would suggest a dominant peripherally mediated mechanism. Our aim is also to evaluate
      impact of remifentanil exposure on esophageal motility and impact of methylnaltrexone alone
      on swallowing function.

      20 healthy volunteers will be studied on two different occasions approximately one week
      apart. In a randomized order volunteers will receive intravenous infusion of remifentanil and
      an intravenous injection of MNTX on one occasion, and placebo (normal saline) infusion and an
      intravenous injection of MNTX on the other occasion. Blood samples are obtained for plasma
      concentration determination of the study drug and sedation levels are assessed during study
      drug exposure.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Pressure Flow pharyngeal variables, 10 ml vs 20 ml bolus
time frame: Up to 60 minutes
description: Difference in pharyngeal pressure flow variables during remifentanil exposure between bolus volumes of 10 ml and 20 ml compared to placebo.
measure: Pressure Flow pharyngeal variables, liquid vs semisolid bolus
time frame: Up to 60 minutes
description: Difference in pharyngeal pressure flow variables during remifentanil exposure between liquid and semisolid boluses compared to placebo
measure: Pressure Flow pharyngeal variables, remifentanil before vs after methylnaltrexone
time frame: Up to 60 minutes
description: Difference in pharyngeal pressure flow variables during remifentanil exposure before and after methylnaltrexone administration compared to placebo.
measure: Pressure Flow pharyngeal variables, placebo before vs after methylnaltrexone
time frame: Up to 60 minutes
description: Difference in pharyngeal pressure flow variables during placebo infusion before and after methylnaltrexone administration.
measure: Pressure Flow esophageal motility variables, 10 ml vs 20 ml bolus
time frame: Up to 60 minutes
description: Difference in variables of esophageal motility between different bolus volumes during remifentanil exposure compared to placebo.
measure: Pressure Flow esophageal motility variables, liquid vs semisolid bolus
time frame: Up to 60 minutes
description: Difference in variables of esophageal motility between liquid and semisolid boluses during remifentanil exposure compared to placebo.
measure: Pressure Flow esophageal motility variables, remifentanil before vs after methylnaltrexone
time frame: Up to 60 minutes
description: Difference in variables of esophageal motility during remifentanil exposure before and after methylnaltrexone administration compared to placebo.
measure: Pressure Flow esophageal motility variables, placebo before vs after methylnaltrexone
time frame: Up to 60 minutes
description: Difference in variables of esophageal motility during placebo infusion before and after methylnaltrexone administration.
arm group label: RemifentanilMNTX
arm group type: Active Comparator
description: Volunteers are given an intravenous infusion with remifentanil, with an effect-site target concentration of 3 ng/ml via a target-controlled infusion (TCI) pump. After a series of swallowing tests an intravenous injection of methylnaltrexone of 0,3 mg/kg is given.
arm group label: PlaceboMNTX
arm group type: Active Comparator
description: Volunteers are given an intravenous infusion with saline 0,9%. After a series of swallowing tests an intravenous injection of methylnaltrexone of 0,3 mg/kg is given.
intervention type: Drug
intervention name: RemifentanilMNTX
description: Remifentanil infusion TCI 3 ng/ml, Methylnaltrexone injection 0.3 mg/kg
arm group label: RemifentanilMNTX
other name: Methylnaltrexone
other name: Remifentanil
other name: Relistor
other name: Ultiva
intervention type: Drug
intervention name: PlaceboMNTX
description: Placebo (NaCl 0.9%) TCI infusion, Methylnaltrexone injection 0.3 mg/kg
arm group label: PlaceboMNTX
other name: Sodium Chloride 0.9%
other name: Methylnaltrexone
other name: Relistor
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Johanna Savilampi, MD, PhD
role: Principal Investigator
affiliation: University hospital in Örebro
last name: Johanna Savilampi, MD, PhD
phone: +46196020266
email: johanna.savilampi@regionorebrolan.se
facility: 
status: Recruiting
contact: 
contact backup: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Region Örebro County
investigator full name: Johanna Savilampi
investigator title: MD, PhD
mesh term: Naltrexone
mesh term: Remifentanil
mesh term: Methylnaltrexone