<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/NCT01689896</url>
  </required_header>
  <id_info>
    <org_study_id>NA_00070640</org_study_id>
    <nct_id>NCT01689896</nct_id>
  </id_info>
  <brief_title>Testosterone and Pain Sensitivity</brief_title>
  <official_title>Effects of Testosterone Replacement on Pain Sensitivity and Pain Perception in Men With Chronic Pain Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Endo Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research is being done to see whether testosterone replacement in men who take&#xD;
      opioid-based pain medications and have low testosterone levels will show improvement in pain&#xD;
      tolerance, pain perception and quality of life.&#xD;
&#xD;
      Some men who take opioid-based medications (narcotics) for pain develop low testosterone&#xD;
      levels. Research has shown that low testosterone levels may make a person more sensitive to&#xD;
      pain. This means that if a person with a painful condition develops low testosterone level as&#xD;
      a result of his pain medications, he might become more sensitive to pain and so may need&#xD;
      higher doses of pain medications for pain control.&#xD;
&#xD;
      Testosterone is a male hormone that is important for sperm production and the development of&#xD;
      male characteristics such as muscle mass and strength, fat distribution, bone mass and sex&#xD;
      drive. Testosterone hormone replacement therapy has been used for decades to treat men with&#xD;
      low testosterone levels (male hypogonadism). Testosterone replacement therapies are available&#xD;
      in the form of an injection into the muscle, implants under the skin, oral capsules taken by&#xD;
      mouth, topical gels applied to the skin, and skin patches.&#xD;
&#xD;
      This study will use Fortesta®, a topical testosterone gel (T-gel) absorbed into the skin.&#xD;
      Fortesta® is currently on the market as an FDA-approved treatment of male hypogonadism (low&#xD;
      testosterone levels).&#xD;
&#xD;
      Men with non-cancer related pain who take opioid-based medications for pain and have low&#xD;
      testosterone levels may join this study. (A low testosterone level is defined as early&#xD;
      morning (before noon) blood testosterone level of 300 ng/dl or less, or a free testosterone&#xD;
      of 50 ng/dl or less)).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Difficult to obtain placebo&#xD;
  </why_stopped>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pain Tolerance - CPT</measure>
    <time_frame>18 weeks</time_frame>
    <description>Cold Pressor Test: Participants will undergo a standard cold pressor task consisting of immersion of the right hand in a 4°C circulating water bath. The standardized instructions for the procedure will direct participants to keep their hands in the water for as long as possible but if the sensations become intolerable participants can remove their hands at any time. At the conclusion of the trial, participants will provide 0-100 ratings of the maximum intensity and unpleasantness of pain produced by water immersion during the trial. During the immersion trial, the time to cold pain threshold (CPTH), pain intensity and tolerance (CPTO) will be recorded.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pain Tolerance - PPT</measure>
    <time_frame>18 Weeks</time_frame>
    <description>Pressure Pain Test: A Somedic algometer will be used to assess responses to noxious mechanical pressure. Pressure is increased steadily at a constant rate until the subject responds by pressing a button, at which point stimulation is terminated. Pressure pain thresholds and tolerances will be assessed 2 times each at 3 body sites bilaterally (the order of which will be randomized): trapezius muscle, masseter muscle, biceps femoris muscle, and ulnar area. For trials of pressure pain threshold, subjects indicate when the stimulus &quot;first feels painful&quot; and for trials of pressure pain tolerance, subjects are asked to respond when the stimulus &quot;becomes intolerable.&quot;</description>
  </primary_outcome>
  <primary_outcome>
    <measure>QOL</measure>
    <time_frame>18 Weeks</time_frame>
    <description>Quality of Life: This parameter will be evaluated using Short Form-36 (SF-36) questionnaire.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pain Tolerance - TPPT</measure>
    <time_frame>18 Weeks</time_frame>
    <description>Thermal Pain Perception Test: Contact heat stimuli will be delivered using a Medoc Thermal Sensory Analyzer, a peltier-element-based stimulator, with the 9 cm2 contact probe applied to the left forearm. The initial thermal assessment procedures include sampling of heat pain thresholds and heat pain tolerances using an ascending method of limits paradigm with a rate of rise of .5°C /Sec.&#xD;
Following, a series of 3 temporal summation procedures will be administered. Sequences of 10 rapid heat pulses are to be applied to the left volar forearm. Target temperatures will be based on subjects' individualized pain thresholds. Subjects will verbally rate the painfulness of each thermal pulse on a 0-100 (0= &quot;no pain&quot;, 100= &quot;most intense pain imaginable&quot;) rating scale. Subjects will be able to terminate the procedure at any time; for those who do, value equivalents to the final rating preceding termination will be assigned to the remaining trials for statistical analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hormonal Outcomes</measure>
    <time_frame>18 Weeks</time_frame>
    <description>Serum will be obtained for serum total and free testosterone, estradiol, prolactin, SHBG, DHEA, FSH, and LH. Bone markers in the form of spot urine N-telopeptides, bone-specific alkaline phosphatase and osteocalcin will be checked, as a measure of bone turnover.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Low Testosterone</condition>
  <condition>Hypogonadism</condition>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Testosterone Gel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Testosterone Gel</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Gel</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo Gel</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Testosterone Gel</intervention_name>
    <arm_group_label>Testosterone Gel</arm_group_label>
    <other_name>Fortesta®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Gel</intervention_name>
    <arm_group_label>Placebo Gel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men&#xD;
&#xD;
          -  18 Years of Age and Older&#xD;
&#xD;
          -  Serum total testosterone level &lt;300 ng/dl or free testosterone &lt; 50 pg/ml&#xD;
&#xD;
          -  Consumption of at least 10 mg of hydrocodone (or analgesic equivalent of another&#xD;
             opioid) for at least 4 weeks&#xD;
&#xD;
          -  Absence of hospitalization in past 2 months&#xD;
&#xD;
          -  No acute illness in past 2 months&#xD;
&#xD;
          -  No prior history of any form of hypogonadism&#xD;
&#xD;
          -  No current anabolic therapy (growth hormone, DHEA, etc)&#xD;
&#xD;
          -  No current use or consumption in past 2 months of glucocorticoids and melatonin&#xD;
&#xD;
          -  Normal digital rectal examination&#xD;
&#xD;
          -  Normal PSA level&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Liver enzymes &gt;3 times upper limit of normal&#xD;
&#xD;
          -  Serum creatinine &gt; 2 times upper limit of normal&#xD;
&#xD;
          -  Neurological disease&#xD;
&#xD;
          -  Active psychiatric illness&#xD;
&#xD;
          -  Any addictive and/or illicit drug use&#xD;
&#xD;
          -  Alcoholism (&gt;10 drinks/week)&#xD;
&#xD;
          -  Patients currently receiving glucocorticoids, melatonin or anabolic agents&#xD;
&#xD;
          -  Hospitalization in past 2 months&#xD;
&#xD;
          -  Acute illness in past 2 months&#xD;
&#xD;
          -  Consumption of &lt; 20 mg of hydrocodone (or analgesic equivalent of another opioid)&#xD;
&#xD;
          -  Severe BPH&#xD;
&#xD;
          -  PSA &gt;4.0 ng/ml&#xD;
&#xD;
          -  Prostate cancer&#xD;
&#xD;
          -  Breast cancer&#xD;
&#xD;
          -  Any cancer or cancer related pain&#xD;
&#xD;
          -  History of alcohol abuse&#xD;
&#xD;
          -  Known peripheral neuropathy (any etiology) or peripheral vascular disease (including&#xD;
             Raynaud's disease), which may interfere with pain testing&#xD;
&#xD;
          -  Concurrent warfarin treatment&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Johns Hopkins Medical Institutions</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>September 11, 2012</study_first_submitted>
  <study_first_submitted_qc>September 18, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <last_update_submitted>March 30, 2015</last_update_submitted>
  <last_update_submitted_qc>March 30, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 31, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Johns Hopkins University</investigator_affiliation>
    <investigator_full_name>Adrian S. Dobs</investigator_full_name>
    <investigator_title>Professor of Medicine and Oncology</investigator_title>
  </responsible_party>
  <keyword>Hypogonadism</keyword>
  <keyword>Low testosterone</keyword>
  <keyword>Pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypogonadism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Testosterone</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/NCT01689896
org study id: NA_00070640
nct id: NCT01689896
lead sponsor: 
collaborator: 
has dmc: No
This research is being done to see whether testosterone replacement in men who take
      opioid-based pain medications and have low testosterone levels will show improvement in pain
      tolerance, pain perception and quality of life.

      Some men who take opioid-based medications (narcotics) for pain develop low testosterone
      levels. Research has shown that low testosterone levels may make a person more sensitive to
      pain. This means that if a person with a painful condition develops low testosterone level as
      a result of his pain medications, he might become more sensitive to pain and so may need
      higher doses of pain medications for pain control.

      Testosterone is a male hormone that is important for sperm production and the development of
      male characteristics such as muscle mass and strength, fat distribution, bone mass and sex
      drive. Testosterone hormone replacement therapy has been used for decades to treat men with
      low testosterone levels (male hypogonadism). Testosterone replacement therapies are available
      in the form of an injection into the muscle, implants under the skin, oral capsules taken by
      mouth, topical gels applied to the skin, and skin patches.

      This study will use Fortesta®, a topical testosterone gel (T-gel) absorbed into the skin.
      Fortesta® is currently on the market as an FDA-approved treatment of male hypogonadism (low
      testosterone levels).

      Men with non-cancer related pain who take opioid-based medications for pain and have low
      testosterone levels may join this study. (A low testosterone level is defined as early
      morning (before noon) blood testosterone level of 300 ng/dl or less, or a free testosterone
      of 50 ng/dl or less)).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Pain Tolerance - CPT
time frame: 18 weeks
description: Cold Pressor Test: Participants will undergo a standard cold pressor task consisting of immersion of the right hand in a 4°C circulating water bath. The standardized instructions for the procedure will direct participants to keep their hands in the water for as long as possible but if the sensations become intolerable participants can remove their hands at any time. At the conclusion of the trial, participants will provide 0-100 ratings of the maximum intensity and unpleasantness of pain produced by water immersion during the trial. During the immersion trial, the time to cold pain threshold (CPTH), pain intensity and tolerance (CPTO) will be recorded.
measure: Pain Tolerance - PPT
time frame: 18 Weeks
description: Pressure Pain Test: A Somedic algometer will be used to assess responses to noxious mechanical pressure. Pressure is increased steadily at a constant rate until the subject responds by pressing a button, at which point stimulation is terminated. Pressure pain thresholds and tolerances will be assessed 2 times each at 3 body sites bilaterally (the order of which will be randomized): trapezius muscle, masseter muscle, biceps femoris muscle, and ulnar area. For trials of pressure pain threshold, subjects indicate when the stimulus "first feels painful" and for trials of pressure pain tolerance, subjects are asked to respond when the stimulus "becomes intolerable."
measure: QOL
time frame: 18 Weeks
description: Quality of Life: This parameter will be evaluated using Short Form-36 (SF-36) questionnaire.
measure: Pain Tolerance - TPPT
time frame: 18 Weeks
description: Thermal Pain Perception Test: Contact heat stimuli will be delivered using a Medoc Thermal Sensory Analyzer, a peltier-element-based stimulator, with the 9 cm2 contact probe applied to the left forearm. The initial thermal assessment procedures include sampling of heat pain thresholds and heat pain tolerances using an ascending method of limits paradigm with a rate of rise of .5°C /Sec.
Following, a series of 3 temporal summation procedures will be administered. Sequences of 10 rapid heat pulses are to be applied to the left volar forearm. Target temperatures will be based on subjects' individualized pain thresholds. Subjects will verbally rate the painfulness of each thermal pulse on a 0-100 (0= "no pain", 100= "most intense pain imaginable") rating scale. Subjects will be able to terminate the procedure at any time; for those who do, value equivalents to the final rating preceding termination will be assigned to the remaining trials for statistical analysis.
measure: Hormonal Outcomes
time frame: 18 Weeks
description: Serum will be obtained for serum total and free testosterone, estradiol, prolactin, SHBG, DHEA, FSH, and LH. Bone markers in the form of spot urine N-telopeptides, bone-specific alkaline phosphatase and osteocalcin will be checked, as a measure of bone turnover.
arm group label: Testosterone Gel
arm group type: Active Comparator
description: Testosterone Gel
arm group label: Placebo Gel
arm group type: Placebo Comparator
description: Placebo Gel
intervention type: Drug
intervention name: Testosterone Gel
arm group label: Testosterone Gel
other name: Fortesta®
intervention type: Drug
intervention name: Placebo Gel
arm group label: Placebo Gel
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Johns Hopkins University
investigator full name: Adrian S. Dobs
investigator title: Professor of Medicine and Oncology
mesh term: Hypogonadism
mesh term: Testosterone