<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/NCT04495452</url>
  </required_header>
  <id_info>
    <org_study_id>IRB-300004738</org_study_id>
    <nct_id>NCT04495452</nct_id>
  </id_info>
  <brief_title>Precision Medicine in Anesthesia</brief_title>
  <official_title>Precision Medicine in Anesthesia: Genetic Component in Opioid-induced Respiratory Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alabama at Birmingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Alabama at Birmingham</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to look at how often a decrease in the rate of breathing occurs after&#xD;
      being given a routinely used intravenous (IV) pain medication. This pain medication&#xD;
      (Fentanyl) is given in the research procedure room by the anesthesiologist. In addition to&#xD;
      relieving pain, in some patients it has been observed that this medication may decrease the&#xD;
      rate of breathing.&#xD;
&#xD;
      Different pieces of one's genetic makeup (also known as genes) can affect how well this&#xD;
      medication relieves pain. The investigators do not know if these same genes influence how&#xD;
      large the effect of the medication has on breathing rate. The purpose of this study is to&#xD;
      determine if the presence or alteration of these same genes may be associated with a decrease&#xD;
      in rate of breathing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Opioids are key analgesic drugs. Unfortunately, they have a high potential for abuse with&#xD;
      potentially lethal consequences, more specifically death due to respiratory suppression. In&#xD;
      both Canada and the US, the number of deaths from opioid overdose continues to rise at an&#xD;
      alarming rate, far exceeding fatalities from motor vehicle accidents in Canada and becoming&#xD;
      the number one cause of unintentional injury-related death in the US. In light of the opioid&#xD;
      epidemic and CDC-scrutiny of opioid use, determining genetic profiles susceptible to&#xD;
      respiratory depression could prove useful in further tailoring the treatment of pain both in&#xD;
      the perioperative setting and in the chronic pain management setting.&#xD;
&#xD;
      The purpose of the proposed study is to evaluate for a genetic component of opioid-induced&#xD;
      respiratory depression. Our overall study hypothesis is that genetic variation influences&#xD;
      opioid-induced respiratory depression.&#xD;
&#xD;
      The primary aim of the study is to correlate an intravenous opioid bolus and genetic&#xD;
      variations of opioid-related target genes. Secondary aims or outcomes are the determination&#xD;
      of general variation in respiratory responses in response to a single intravenous fentanyl&#xD;
      bolus. Other observed effects are age and gender related differences, the effect of a single&#xD;
      fentanyl bolus on alertness, the incidence of emesis and opioid effects on micturition as&#xD;
      determined by the modified Aldrete discharge criteria.&#xD;
&#xD;
      Based on existing work on genetic determinants of opioid receptor effects, we propose to&#xD;
      correlate clinical parameters of respiratory depression (proportional reduction in&#xD;
      respiratory minute ventilation) with the expression of single-nucleotide polymorphisms (SNPs)&#xD;
      of genes related to opioid-induced analgesia. We propose to identify a subset of participants&#xD;
      with the most significant respiratory depression and contrast those with participants that&#xD;
      exhibit no respiratory effects. The blood samples from these two groups will be used to&#xD;
      compare genetic variances of genes related to opioid-induced analgesia.&#xD;
&#xD;
      This will be a collaborative project between the clinical physicians and basic scientists in&#xD;
      an effort to better characterize opioid-induced respiratory depression. We believe this work&#xD;
      will be valuable as a means to prevent and treat opioid toxicity and guide development of&#xD;
      safer approaches to opioid therapy and drug development.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">December 10, 2023</start_date>
  <completion_date type="Anticipated">September 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 10, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Respiratory rate</measure>
    <time_frame>From the time of administration of study medication to 10 minutes after study medication administration</time_frame>
    <description>A decrease in breathing frequency as quantified by respiratory rate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Minute Ventilation</measure>
    <time_frame>From the time of administration of study medication to 10 minutes after study medication administration</time_frame>
    <description>A decrease in breathing as quantified by minute ventilation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Occlusion Pressure</measure>
    <time_frame>From the time of administration of study medication to 10 minutes after study medication administration</time_frame>
    <description>A measure of respiratory depression as quantified by occlusion pressure</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Respiratory Depression</condition>
  <arm_group>
    <arm_group_label>Study Participants</arm_group_label>
    <description>We will be enrolling 200 participants, this will provide a large enough sampling to assure there are at least 25 patients with significant respiratory depression and 25 with insignificant respiratory depression.&#xD;
The genetic data from participants with the most respiratory depression defined as having a 20-40% decrease from initial respiratory parameters will be compared with genetic data from participants with the least respiratory depression defined as having no change or less than 10% decrease from initial respiratory parameters.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fentanyl Drug Administration</intervention_name>
    <description>Subjects will be given a standardized dose of fentanyl 2.5 mcg/kg estimated ideal body weight (males: ideal body weight = 50 kg + 2.3 kg for each inch over 5 feet. Females: Ideal body weight = 45.5 kg + 2.3 kg for each inch over 5 feet).</description>
    <arm_group_label>Study Participants</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      A blood sample (about 10 mL) will be collected either during the IV line insertion or after&#xD;
      fentanyl administration during the recovery period&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        This study will involve adult human volunteers, representative of the greater Alabama&#xD;
        population.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy Subjects&#xD;
&#xD;
          -  older than 19&#xD;
&#xD;
          -  able to follow the study instructions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any medical condition that could affect study procedures or potentially put the&#xD;
             subject at risk, in the opinion of the investigators&#xD;
&#xD;
          -  age less than 18 or older than 40&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  obesity&#xD;
&#xD;
          -  sleep apnea&#xD;
&#xD;
          -  pulmonary problems such as moderate or severe bronchial asthma&#xD;
&#xD;
          -  epilepsy&#xD;
&#xD;
          -  chronic analgesic medication&#xD;
&#xD;
          -  history of surgery for which details are unavailable&#xD;
&#xD;
          -  allergy to fentanyl&#xD;
&#xD;
          -  history of drug abuse&#xD;
&#xD;
          -  positive urine test for illicit drugs&#xD;
&#xD;
          -  female participants will be scheduled for a urine pregnancy test on the day of the&#xD;
             procedure, prior to receiving study medication, only subjects with negative tests will&#xD;
             continue&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alethia Sellers, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alabama at Birmingham</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Adam Sturdivant, MPH</last_name>
    <phone>205-934-4042</phone>
    <email>Adamsturdivant@uabmc.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ayesha Bryant, MD, MSPH</last_name>
    <phone>205-934-4969</phone>
  </overall_contact_backup>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>April 27, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <last_update_submitted>May 23, 2023</last_update_submitted>
  <last_update_submitted_qc>May 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Alabama at Birmingham</investigator_affiliation>
    <investigator_full_name>Alethia Sellers</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Insufficiency</mesh_term>
    <mesh_term>Depression</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fentanyl</mesh_term>
  </intervention_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/NCT04495452
org study id: IRB-300004738
nct id: NCT04495452
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This study is designed to look at how often a decrease in the rate of breathing occurs after
      being given a routinely used intravenous (IV) pain medication. This pain medication
      (Fentanyl) is given in the research procedure room by the anesthesiologist. In addition to
      relieving pain, in some patients it has been observed that this medication may decrease the
      rate of breathing.

      Different pieces of one's genetic makeup (also known as genes) can affect how well this
      medication relieves pain. The investigators do not know if these same genes influence how
      large the effect of the medication has on breathing rate. The purpose of this study is to
      determine if the presence or alteration of these same genes may be associated with a decrease
      in rate of breathing.
Opioids are key analgesic drugs. Unfortunately, they have a high potential for abuse with
      potentially lethal consequences, more specifically death due to respiratory suppression. In
      both Canada and the US, the number of deaths from opioid overdose continues to rise at an
      alarming rate, far exceeding fatalities from motor vehicle accidents in Canada and becoming
      the number one cause of unintentional injury-related death in the US. In light of the opioid
      epidemic and CDC-scrutiny of opioid use, determining genetic profiles susceptible to
      respiratory depression could prove useful in further tailoring the treatment of pain both in
      the perioperative setting and in the chronic pain management setting.

      The purpose of the proposed study is to evaluate for a genetic component of opioid-induced
      respiratory depression. Our overall study hypothesis is that genetic variation influences
      opioid-induced respiratory depression.

      The primary aim of the study is to correlate an intravenous opioid bolus and genetic
      variations of opioid-related target genes. Secondary aims or outcomes are the determination
      of general variation in respiratory responses in response to a single intravenous fentanyl
      bolus. Other observed effects are age and gender related differences, the effect of a single
      fentanyl bolus on alertness, the incidence of emesis and opioid effects on micturition as
      determined by the modified Aldrete discharge criteria.

      Based on existing work on genetic determinants of opioid receptor effects, we propose to
      correlate clinical parameters of respiratory depression (proportional reduction in
      respiratory minute ventilation) with the expression of single-nucleotide polymorphisms (SNPs)
      of genes related to opioid-induced analgesia. We propose to identify a subset of participants
      with the most significant respiratory depression and contrast those with participants that
      exhibit no respiratory effects. The blood samples from these two groups will be used to
      compare genetic variances of genes related to opioid-induced analgesia.

      This will be a collaborative project between the clinical physicians and basic scientists in
      an effort to better characterize opioid-induced respiratory depression. We believe this work
      will be valuable as a means to prevent and treat opioid toxicity and guide development of
      safer approaches to opioid therapy and drug development.
observational model: Cohort
time perspective: Prospective
measure: Respiratory rate
time frame: From the time of administration of study medication to 10 minutes after study medication administration
description: A decrease in breathing frequency as quantified by respiratory rate
measure: Minute Ventilation
time frame: From the time of administration of study medication to 10 minutes after study medication administration
description: A decrease in breathing as quantified by minute ventilation
measure: Occlusion Pressure
time frame: From the time of administration of study medication to 10 minutes after study medication administration
description: A measure of respiratory depression as quantified by occlusion pressure
arm group label: Study Participants
description: We will be enrolling 200 participants, this will provide a large enough sampling to assure there are at least 25 patients with significant respiratory depression and 25 with insignificant respiratory depression.
The genetic data from participants with the most respiratory depression defined as having a 20-40% decrease from initial respiratory parameters will be compared with genetic data from participants with the least respiratory depression defined as having no change or less than 10% decrease from initial respiratory parameters.
intervention type: Drug
intervention name: Fentanyl Drug Administration
description: Subjects will be given a standardized dose of fentanyl 2.5 mcg/kg estimated ideal body weight (males: ideal body weight = 50 kg + 2.3 kg for each inch over 5 feet. Females: Ideal body weight = 45.5 kg + 2.3 kg for each inch over 5 feet).
arm group label: Study Participants
A blood sample (about 10 mL) will be collected either during the IV line insertion or after
      fentanyl administration during the recovery period
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 19 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Alethia Sellers, MD
role: Principal Investigator
affiliation: University of Alabama at Birmingham
last name: Adam Sturdivant, MPH
phone: 205-934-4042
email: Adamsturdivant@uabmc.edu
last name: Ayesha Bryant, MD, MSPH
phone: 205-934-4969
responsible party type: Principal Investigator
investigator affiliation: University of Alabama at Birmingham
investigator full name: Alethia Sellers
investigator title: Principal Investigator
mesh term: Respiratory Insufficiency
mesh term: Depression
mesh term: Fentanyl
sharing ipd: No