<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/NCT04421209</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00103364</org_study_id>
    <nct_id>NCT04421209</nct_id>
  </id_info>
  <brief_title>Analgesic Effects of Perioperative Propranolol Administration for Spine Surgery</brief_title>
  <official_title>Analgesic Effects of Perioperative Propranolol Administration for Spine Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Foundation for Anesthesia Education and Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if treatment with low-dose oral propranolol in the&#xD;
      days before and after surgery decrease postoperative pain and improve pain scores.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a randomized, double-blind, placebo controlled clinical trial.The main purpose&#xD;
      of this study is to determine if postsurgical opioid use and pain scores are decreased with&#xD;
      oral Propranolol treatment. The treatment period will last for six days and the observation&#xD;
      period will last for three months. Effectiveness of treatment will be assessed by means of&#xD;
      post-operative opioid consumption as primary outcome measure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No funding source&#xD;
  </why_stopped>
  <start_date type="Anticipated">December 2020</start_date>
  <completion_date type="Anticipated">September 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2021</primary_completion_date>
  <phase>Phase 2</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Acute postoperative opioid use at 24 hours</measure>
    <time_frame>24 hours postoperatively</time_frame>
    <description>Total opioid use from 0 to 24 hours post-op will be quantified. Opioid doses administered via all routes will be converted to standard oral morphine equivalents (OME).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Acute postoperative opioid use at 48 hours</measure>
    <time_frame>48 hours postoperatively</time_frame>
    <description>Total opioid use from 24 to 48 hours post-op will be quantified. Opioid doses administered via all routes will be converted to standard oral morphine equivalents (OME).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sub-acute postoperative opioid use at 1 week</measure>
    <time_frame>1 week postoperatively</time_frame>
    <description>Patient reported current opioid use for the prior 24 hours will be quantified at 1 week post-op. Opioid use will be converted to standard oral morphine equivalents (OME).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sub-acute postoperative opioid use at 4 weeks</measure>
    <time_frame>4 weeks postoperatively</time_frame>
    <description>Patient reported current opioid use for the prior 24 hours will be quantified at 4 weeks post-op. Opioid use will be converted to standard oral morphine equivalents (OME).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sub-acute postoperative opioid use at 12 weeks</measure>
    <time_frame>12 weeks postoperatively</time_frame>
    <description>Patient reported current opioid use for the prior 24 hours will be quantified at 12 weeks post-op. Opioid use will be converted to standard oral morphine equivalents (OME).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute postoperative pain scores at 24 hours</measure>
    <time_frame>24 hours post-op</time_frame>
    <description>The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 24 post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute postoperative pain scores at 48 hours</measure>
    <time_frame>48 hours post-op</time_frame>
    <description>The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 48 hours post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sub-acute postoperative pain scores at 1 week</measure>
    <time_frame>1 week postoperatively</time_frame>
    <description>The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 1 week post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sub-acute postoperative pain scores at 4 weeks</measure>
    <time_frame>4 weekspostoperatively</time_frame>
    <description>The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 4 week post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sub-acute postoperative pain scores at 12 weeks</measure>
    <time_frame>12 weeks postoperatively</time_frame>
    <description>The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 12 weeks post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Lumbar Disc Disease</condition>
  <condition>Spinal Fusion</condition>
  <condition>Degenerative Disc Disease</condition>
  <arm_group>
    <arm_group_label>Propranolol treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects randomized to the propranolol treatment arm will be administered propranolol 40mg BID for three days prior to surgery, 40mg BID the day of surgery and on post-operative days 1 and 2. Subjects and researchers will be blinded and will not know if propranolol or placebo control is administered.&#xD;
Patients will be evaluated for opioid usend pain scores at 24 hrs, 48 hrs, 1 week, 4 weeks, and 12 weeks post-op.&#xD;
Blood will also be obtained pre-operatively, 8 hours and 24 hours post-operatively to measure the level of inflammatory markers. We will use these samples to evaluate if treatment with propranolol decreases the levels of inflammatory markers, and if this correlates to decreased opioid use and pain scores post-operatively.&#xD;
All other pre-, intra-, and post-operative interventions will be equivalent between the experimental and placebo groups, and this study's interventions will not affect surgical management.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects randomized to the placebo treatment arm will be administered placebo tablets with the same schedule as propranolol in the experimental arm. Subjects and researchers will be blinded and will not know if propranolol or placebo control is administered.&#xD;
Patients will be evaluated for opioid use and pain scores at 24 hrs, 48 hrs, 1 week, 4 weeks, and 12 weeks post-op.&#xD;
Blood will also be obtained pre-operatively, 8 hours and 24 hours post-operatively to measure the level of inflammatory markers. We will use these samples to evaluate if treatment with propranolol decreases the levels of inflammatory markers compared to placebo, and if this correlates to decreased opioid use and pain scores post-operatively.&#xD;
All other pre-, intra-, and post-operative interventions will be equivalent between the experimental and placebo groups, and this study's interventions will not affect surgical management.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propranolol Hcl 40mg Tab</intervention_name>
    <description>40mg PO BID for the three days prior to surgery, 40mg PO BID the day of surgery and on post-op days 1 and 2.</description>
    <arm_group_label>Propranolol treatment</arm_group_label>
    <other_name>CAS No 525-66-6</other_name>
    <other_name>DIN: 00496499</other_name>
    <other_name>Inderal</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral tablet</intervention_name>
    <description>Placebo tablets administered with the same schedule of Propranolol tablets</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Tablet containing microcrystalline dextrose</other_name>
    <other_name>Sugar pill, dextrose pill</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patients age &gt;18 undergoing elective spinal fusion surgery, with plans&#xD;
             to remain inpatient for ≥ 48hrs and receive IV or oral opioids;&#xD;
&#xD;
          -  Females of child bearing potential must test negative on a pregnancy test at Visit 1&#xD;
             and utilize acceptable means of birth control for the duration of the study;&#xD;
&#xD;
          -  Patients must be judged by the study team to be likely to be reliable and to agree to&#xD;
             keep all appointments for clinic visits, tests, and procedures required by the&#xD;
             protocol;&#xD;
&#xD;
          -  Patients must have the ability to fully participate in the informed consent process.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Disease-related: History of exercise- or exertion-induced asthma or current treatments&#xD;
             for asthma; Unstable medical or neurological illness; Heart block greater than first&#xD;
             degree (EKG); History of coronary artery disease, or history of congestive heart&#xD;
             failure; Baseline heart rate or blood pressure that in the opinion of the investigator&#xD;
             would constitute too great a risk when considered in the context of the patient's&#xD;
             medical comorbidities and health history; Significant suicidal or homicidal ideation,&#xD;
             or current DSM-IV diagnosis of bipolar disorder, schizophrenia or other psychotic&#xD;
             disorder, or cognitive disorder due to a general medical condition; History of&#xD;
             diabetes&#xD;
&#xD;
          -  Exposure-related: History of β-blocker use within six months of enrollment in the&#xD;
             trial; Total baseline preoperative opioid consumption greater than 50 oral milligram&#xD;
             morphine equivalents (MME) per day; Current use or use within the past two weeks of&#xD;
             methadone, levorphanol, buprenorphine, butorphanol, pentazocine, tramadol, nalbuphine,&#xD;
             naloxone, or naltrexone.&#xD;
&#xD;
          -  Patient characteristics: Female patients who are pregnant or breast-feeding; Known&#xD;
             allergy to study medication; Alcohol/substance abuse within past six months; Ongoing&#xD;
             or anticipated disability compensation or litigation issues, in the best judgement of&#xD;
             the investigator; Presence of any factors/conditions, medical or other, that in the&#xD;
             judgment of the investigator may interfere with performance of study outcome measures,&#xD;
             such as treatment-refractory history; Non-ambulatory or require the use of crutches or&#xD;
             a walker; No access to a telephone&#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>Thomas Buchheit, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Anesthesiology, Duke University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stephan Frangakis, MD/PhD</last_name>
    <role>Study Director</role>
    <affiliation>Department of Anesthesiology, Duke University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>William Maixner, DDS/PhD</last_name>
    <role>Study Director</role>
    <affiliation>Department of Anesthesiology, Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Hospital</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Afify EA, Andijani NM. Potentiation of Morphine-Induced Antinociception by Propranolol: The Involvement of Dopamine and GABA Systems. Front Pharmacol. 2017 Nov 10;8:794. doi: 10.3389/fphar.2017.00794. eCollection 2017.</citation>
    <PMID>29209205</PMID>
  </reference>
  <reference>
    <citation>Ciszek BP, O'Buckley SC, Nackley AG. Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral beta-Adrenergic Receptors. Anesthesiology. 2016 May;124(5):1122-35. doi: 10.1097/ALN.0000000000001070.</citation>
    <PMID>26950706</PMID>
  </reference>
  <reference>
    <citation>Gan TJ, Habib AS, Miller TE, White W, Apfelbaum JL. Incidence, patient satisfaction, and perceptions of post-surgical pain: results from a US national survey. Curr Med Res Opin. 2014 Jan;30(1):149-60. doi: 10.1185/03007995.2013.860019. Epub 2013 Nov 15.</citation>
    <PMID>24237004</PMID>
  </reference>
  <reference>
    <citation>Hartung JE, Ciszek BP, Nackley AG. beta2- and beta3-adrenergic receptors drive COMT-dependent pain by increasing production of nitric oxide and cytokines. Pain. 2014 Jul;155(7):1346-1355. doi: 10.1016/j.pain.2014.04.011. Epub 2014 Apr 13.</citation>
    <PMID>24727346</PMID>
  </reference>
  <reference>
    <citation>Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. doi: 10.1016/S0140-6736(06)68700-X.</citation>
    <PMID>16698416</PMID>
  </reference>
  <reference>
    <citation>Krebs EE, Lorenz KA, Bair MJ, Damush TM, Wu J, Sutherland JM, Asch SM, Kroenke K. Development and initial validation of the PEG, a three-item scale assessing pain intensity and interference. J Gen Intern Med. 2009 Jun;24(6):733-8. doi: 10.1007/s11606-009-0981-1. Epub 2009 May 6.</citation>
    <PMID>19418100</PMID>
  </reference>
  <reference>
    <citation>Light KC, Bragdon EE, Grewen KM, Brownley KA, Girdler SS, Maixner W. Adrenergic dysregulation and pain with and without acute beta-blockade in women with fibromyalgia and temporomandibular disorder. J Pain. 2009 May;10(5):542-52. doi: 10.1016/j.jpain.2008.12.006.</citation>
    <PMID>19411061</PMID>
  </reference>
  <reference>
    <citation>Nackley AG, Tan KS, Fecho K, Flood P, Diatchenko L, Maixner W. Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta2- and beta3-adrenergic receptors. Pain. 2007 Apr;128(3):199-208. doi: 10.1016/j.pain.2006.09.022. Epub 2006 Nov 7.</citation>
    <PMID>17084978</PMID>
  </reference>
  <reference>
    <citation>Page MG, Kudrina I, Zomahoun HTV, Ziegler D, Beaulieu P, Charbonneau C, Cogan J, Daoust R, Martel MO, Neron A, Richebe P, Clarke H. Relative frequency and risk factors for long-term opioid therapy following surgery and trauma among adults: a systematic review protocol. Syst Rev. 2018 Jul 18;7(1):97. doi: 10.1186/s13643-018-0760-3.</citation>
    <PMID>30021647</PMID>
  </reference>
  <reference>
    <citation>Stanley TH, de Lange S, Boscoe MJ, de Bruijn N. The influence of chronic preoperative propranolol therapy on cardiovascular dynamics and narcotic requirements during operation in patients with coronary artery disease. Can Anaesth Soc J. 1982 Jul;29(4):319-24. doi: 10.1007/BF03007519.</citation>
    <PMID>6213289</PMID>
  </reference>
  <reference>
    <citation>Tchivileva IE, Lim PF, Smith SB, Slade GD, Diatchenko L, McLean SA, Maixner W. Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study. Pharmacogenet Genomics. 2010 Apr;20(4):239-48. doi: 10.1097/FPC.0b013e328337f9ab.</citation>
    <PMID>20216107</PMID>
  </reference>
  <reference>
    <citation>Teimoori, B., Khoshfetrat, M., Beyrami, F., Sakhavar, N., Dehbashi, Z., Narouie, B., &amp; Davarian, A. Propranolol decreases the post-operative pain and analgesic administration following abdominal hysterectomy. Life Sciences Journal 9: 1216-1220, 2012.</citation>
  </reference>
  <reference>
    <citation>Zanelatto FB, Dias EV, Teixeira JM, Sartori CR, Parada CA, Tambeli CH. Anti-inflammatory effects of propranolol in the temporomandibular joint of female rats and its contribution to antinociceptive action. Eur J Pain. 2018 Mar;22(3):572-582. doi: 10.1002/ejp.1143. Epub 2017 Dec 11.</citation>
    <PMID>29226500</PMID>
  </reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>March 12, 2021</last_update_submitted>
  <last_update_submitted_qc>March 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>lumbar fusion</keyword>
  <keyword>propranolol</keyword>
  <keyword>beta-blockers</keyword>
  <keyword>post-surgical pain</keyword>
  <keyword>opioid-sparing</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Diseases</mesh_term>
    <mesh_term>Intervertebral Disc Degeneration</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Propranolol</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/NCT04421209
org study id: Pro00103364
nct id: NCT04421209
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to determine if treatment with low-dose oral propranolol in the
      days before and after surgery decrease postoperative pain and improve pain scores.
This study is a randomized, double-blind, placebo controlled clinical trial.The main purpose
      of this study is to determine if postsurgical opioid use and pain scores are decreased with
      oral Propranolol treatment. The treatment period will last for six days and the observation
      period will last for three months. Effectiveness of treatment will be assessed by means of
      post-operative opioid consumption as primary outcome measure.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Acute postoperative opioid use at 24 hours
time frame: 24 hours postoperatively
description: Total opioid use from 0 to 24 hours post-op will be quantified. Opioid doses administered via all routes will be converted to standard oral morphine equivalents (OME).
measure: Acute postoperative opioid use at 48 hours
time frame: 48 hours postoperatively
description: Total opioid use from 24 to 48 hours post-op will be quantified. Opioid doses administered via all routes will be converted to standard oral morphine equivalents (OME).
measure: Sub-acute postoperative opioid use at 1 week
time frame: 1 week postoperatively
description: Patient reported current opioid use for the prior 24 hours will be quantified at 1 week post-op. Opioid use will be converted to standard oral morphine equivalents (OME).
measure: Sub-acute postoperative opioid use at 4 weeks
time frame: 4 weeks postoperatively
description: Patient reported current opioid use for the prior 24 hours will be quantified at 4 weeks post-op. Opioid use will be converted to standard oral morphine equivalents (OME).
measure: Sub-acute postoperative opioid use at 12 weeks
time frame: 12 weeks postoperatively
description: Patient reported current opioid use for the prior 24 hours will be quantified at 12 weeks post-op. Opioid use will be converted to standard oral morphine equivalents (OME).
measure: Acute postoperative pain scores at 24 hours
time frame: 24 hours post-op
description: The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 24 post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.
measure: Acute postoperative pain scores at 48 hours
time frame: 48 hours post-op
description: The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 48 hours post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.
measure: Sub-acute postoperative pain scores at 1 week
time frame: 1 week postoperatively
description: The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 1 week post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.
measure: Sub-acute postoperative pain scores at 4 weeks
time frame: 4 weekspostoperatively
description: The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 4 week post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.
measure: Sub-acute postoperative pain scores at 12 weeks
time frame: 12 weeks postoperatively
description: The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 12 weeks post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.
arm group label: Propranolol treatment
arm group type: Experimental
description: Subjects randomized to the propranolol treatment arm will be administered propranolol 40mg BID for three days prior to surgery, 40mg BID the day of surgery and on post-operative days 1 and 2. Subjects and researchers will be blinded and will not know if propranolol or placebo control is administered.
Patients will be evaluated for opioid usend pain scores at 24 hrs, 48 hrs, 1 week, 4 weeks, and 12 weeks post-op.
Blood will also be obtained pre-operatively, 8 hours and 24 hours post-operatively to measure the level of inflammatory markers. We will use these samples to evaluate if treatment with propranolol decreases the levels of inflammatory markers, and if this correlates to decreased opioid use and pain scores post-operatively.
All other pre-, intra-, and post-operative interventions will be equivalent between the experimental and placebo groups, and this study's interventions will not affect surgical management.
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects randomized to the placebo treatment arm will be administered placebo tablets with the same schedule as propranolol in the experimental arm. Subjects and researchers will be blinded and will not know if propranolol or placebo control is administered.
Patients will be evaluated for opioid use and pain scores at 24 hrs, 48 hrs, 1 week, 4 weeks, and 12 weeks post-op.
Blood will also be obtained pre-operatively, 8 hours and 24 hours post-operatively to measure the level of inflammatory markers. We will use these samples to evaluate if treatment with propranolol decreases the levels of inflammatory markers compared to placebo, and if this correlates to decreased opioid use and pain scores post-operatively.
All other pre-, intra-, and post-operative interventions will be equivalent between the experimental and placebo groups, and this study's interventions will not affect surgical management.
intervention type: Drug
intervention name: Propranolol Hcl 40mg Tab
description: 40mg PO BID for the three days prior to surgery, 40mg PO BID the day of surgery and on post-op days 1 and 2.
arm group label: Propranolol treatment
other name: CAS No 525-66-6
other name: DIN: 00496499
other name: Inderal
intervention type: Drug
intervention name: Placebo oral tablet
description: Placebo tablets administered with the same schedule of Propranolol tablets
arm group label: Placebo
other name: Tablet containing microcrystalline dextrose
other name: Sugar pill, dextrose pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thomas Buchheit, MD
role: Principal Investigator
affiliation: Department of Anesthesiology, Duke University
last name: Stephan Frangakis, MD/PhD
role: Study Director
affiliation: Department of Anesthesiology, Duke University
last name: William Maixner, DDS/PhD
role: Study Director
affiliation: Department of Anesthesiology, Duke University
facility: 
country: United States
citation: Afify EA, Andijani NM. Potentiation of Morphine-Induced Antinociception by Propranolol: The Involvement of Dopamine and GABA Systems. Front Pharmacol. 2017 Nov 10;8:794. doi: 10.3389/fphar.2017.00794. eCollection 2017.
PMID: 29209205
citation: Ciszek BP, O'Buckley SC, Nackley AG. Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral beta-Adrenergic Receptors. Anesthesiology. 2016 May;124(5):1122-35. doi: 10.1097/ALN.0000000000001070.
PMID: 26950706
citation: Gan TJ, Habib AS, Miller TE, White W, Apfelbaum JL. Incidence, patient satisfaction, and perceptions of post-surgical pain: results from a US national survey. Curr Med Res Opin. 2014 Jan;30(1):149-60. doi: 10.1185/03007995.2013.860019. Epub 2013 Nov 15.
PMID: 24237004
citation: Hartung JE, Ciszek BP, Nackley AG. beta2- and beta3-adrenergic receptors drive COMT-dependent pain by increasing production of nitric oxide and cytokines. Pain. 2014 Jul;155(7):1346-1355. doi: 10.1016/j.pain.2014.04.011. Epub 2014 Apr 13.
PMID: 24727346
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responsible party type: Sponsor
mesh term: Spinal Diseases
mesh term: Intervertebral Disc Degeneration
mesh term: Propranolol
sharing ipd: No