<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/NCT02986334</url>
  </required_header>
  <id_info>
    <org_study_id>STU00080585 (Phase 2)</org_study_id>
    <secondary_id>5R01AT007987-03</secondary_id>
    <nct_id>NCT02986334</nct_id>
  </id_info>
  <brief_title>Placebo In Chronic Back Pain (Phase 2)</brief_title>
  <acronym>PICP2</acronym>
  <official_title>Brain Mechanisms For Clinical Placebo in Chronic Pain: A Randomized Clinical Trial of Placebo, Active Treatment, and No Treatment in Chronic Back Pain</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Apkar Apkarian</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Center for Complementary and Integrative Health (NCCIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Northwestern University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to examine brain properties for placebo response in chronic back pain&#xD;
      patients. The investigators have preliminary data indicating that, in blinded clinical trial&#xD;
      studies with neutral instructions regarding treatment, chronic back pain (CBP) patients can&#xD;
      be subdivided into placebo responders and non-responders, and these differences are&#xD;
      PREDICTABLE a priori, by brain activity. The results imply that CBP placebo may have clinical&#xD;
      utility and that its properties can be studied by human brain imaging techniques. In Phase I&#xD;
      of the study, the investigators seek to identify brain imaging parameters that predict the&#xD;
      propensity for the placebo response in an independent CBP cohort. In Phase II, the&#xD;
      investigators will evaluate the interaction between placebo response and medication treatment&#xD;
      in individuals stratified as placebo responders versus non-responders. This research is&#xD;
      designed to critically assess the neurobiology of placebo analgesia for chronic pain in a&#xD;
      partially-blind clinical trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Visit 1 (week -3): Screening visit (90 min):&#xD;
&#xD;
      Participants will be evaluated with inclusion/exclusion criteria and complete the informed&#xD;
      consent documents. A medical/pain history will be taken and physical exam will be completed&#xD;
      by a physician and participants will be asked to rate their current back pain intensity.&#xD;
      Participants will complete a set of 10 questionnaires that will ask about health and medical&#xD;
      history, past and current pain levels, personality, and emotions. Participants will be&#xD;
      allowed to take breaks and walk around during this time so that participants don't get tired&#xD;
      while filling out questionnaires. Finally, participants will have blood drawn for screening&#xD;
      purposes including to see if kidneys and liver are functioning as they should (the&#xD;
      investigators will take 40 mL or about 8 teaspoons). Participants will be asked to return in&#xD;
      2 weeks for baseline magnetic resonance imaging (MRI) scans. Participants will be asked to&#xD;
      discontinue current pain medications 14 days prior to Visit 2 and take only the rescue&#xD;
      medication (&quot;rescue&quot; medication that is also known as acetaminophen/Tylenol ®), given for&#xD;
      pain during this time (see below) - this is so that the investigators can assess baseline&#xD;
      amount of pain. Participants will be informed that they may be randomized in the placebo&#xD;
      group and/or the no-treatment group (Visit 3) once one qualifies to continue in the study.&#xD;
      Participants must, therefore,a be willing and able to stop taking the medication for pain for&#xD;
      up to a maximum of 12 weeks during this study. Participants will be given acetaminophen (500&#xD;
      mg, up to 4 times per day) to take for pain relief (as rescue medication), a dose that can be&#xD;
      continued throughout the study. Participants are free to stop participation at any point in&#xD;
      the study. Participants randomized into the treatment arm may receive the anti-inflammatory&#xD;
      drug naproxen, since it is known to increase the risk of stomach and intestinal side effects,&#xD;
      a combined naproxen/esomeprazole drug regimen will be given to participants to provide some&#xD;
      protection for these types of side effects.&#xD;
&#xD;
      Visit 2 (week -1): Baseline Scan (90 min):&#xD;
&#xD;
      Participants will rate their pain intensity, complete questionnaires, and undergo brain&#xD;
      scanning (anatomical and functional scans). Participants will receive medication, which can&#xD;
      be used if the pain becomes too much to handle (500 mg four times per day maximum). The&#xD;
      researcher will ask participants about how often participants used the &quot;rescue&quot; medication&#xD;
      and any changes in health they may have experienced since the last visit.&#xD;
&#xD;
      Visit 3 (week 0): Start of Treatment Period and Randomization (30-45 min):&#xD;
&#xD;
      Participants will rate their pain intensity and complete questionnaires. Participants will be&#xD;
      randomized into either a drug (placebo or naproxen and esomeprazole) treatment group or no&#xD;
      treatment group; if participants are assigned to a treatment group (active or placebo),&#xD;
      neither participants nor the clinical coordinator/assistant will know which group&#xD;
      participants are allocated in. Enough medication will be given to participants to last until&#xD;
      the next visit. The placebo group will receive two placebo capsules twice daily and the&#xD;
      active drug group will receive one naproxen capsule (500mg) and one esomeprazole capsule&#xD;
      (20mg) twice daily (morning and night) for the treatment period. The medication (Naproxen or&#xD;
      Placebo) needs to be taken with at least one full glass (8 oz) of water and the other&#xD;
      medication (Esomeprazole or Placebo) should be taken one hour before a meal. The researcher&#xD;
      will provide the study medication; if participants were randomized into the no treatment&#xD;
      group, participants will only receive rescue medication. The researcher will ask participants&#xD;
      about how often participants used the &quot;rescue&quot; medication and any side effects participants&#xD;
      experienced since Visit 2 took place. Additional &quot;rescue&quot; medication will be given.&#xD;
&#xD;
      Visit 4 (week 3): Continuing Assessment (30-45 min). The procedures described for Visit 3&#xD;
      will be repeated during this visit. The researcher will ask participants about how often they&#xD;
      used the &quot;rescue&quot; medication and any side effects experienced since Visit 3 took place. As&#xD;
      well, the researcher will ask how often participants took the study medication (if in a&#xD;
      treatment group) and document the total pills ingested.&#xD;
&#xD;
      Visit 5 (week 6): End of Treatment/Start of Washout and Final Scan (60-90 min):&#xD;
&#xD;
      The procedures described for Visit 2 will be repeated during this visit. The researcher will&#xD;
      ask participants about how often and reliably participants took the medication (if in a&#xD;
      treatment group), as well as how often they used the &quot;rescue&quot; medication and any side effects&#xD;
      experienced since Visit 4 took place. Participants will only receive the &quot;rescue&quot; medication&#xD;
      for the upcoming 3 weeks.&#xD;
&#xD;
      Visit 6 (week 9): Final Visit/End of Washout (30-45 min):&#xD;
&#xD;
      Participants will return to complete questionnaires, but no brain scans will be done. The&#xD;
      researcher will ask participants about how often they used the &quot;rescue&quot; medication and any&#xD;
      side effects experienced since Visit 5 took place. If participants are in one of the&#xD;
      treatment groups, participants will be asked to return all of the study medication and rescue&#xD;
      medication at this time, and all treatment will be stopped at this visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2016</start_date>
  <completion_date type="Actual">June 2018</completion_date>
  <primary_completion_date type="Actual">June 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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Change in Pain Assessed by Visual Analogue Scale (VAS)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Self-report pain using a VAS scale (0-10) : 0 represents no pain and 10 the worst imaginable pain.&#xD;
Results are presented as percentage (%) change in pain before and after the intervention (baseline and post-intervention, 12 weeks).&#xD;
Percentage change is calculated with post-intervention pain minus baseline pain, divided by baseline pain i.e. (post - baseline) / baseline.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">94</enrollment>
  <condition>Chronic Low Back Pain</condition>
  <arm_group>
    <arm_group_label>No Treatment Intervention</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Observational Subjects randomized to this arm will be asked to discontinue their current pain medications for the length of the study. This arm is not blinded, as both study staff and participants will be aware that they are not receiving a study treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active Treatment Intervention</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Naproxen &amp; Omeprazole Subjects randomized to this arm will be asked to discontinue their current pain medications and take one 500mg naproxen capsule and one 40mg omeprazole capsule twice a day for the length of the study. This arm is double-blind, as neither participants nor study staff will know what medication the participants is receiving (blind to active versus placebo treatment).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Treatment Intervention</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects randomized to this arm will be asked to discontinue their current pain medications and take two placebo capsules twice a day for the length of the study. This arm is double-blind, as neither participants nor study staff will know what medication the participants is receiving (blind to active versus placebo treatment)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Naproxen</intervention_name>
    <description>Subjects enrolled in the active treatment arm will receive 500mg of Naproxen prescribed twice daily, once in the morning and evening.</description>
    <arm_group_label>Active Treatment Intervention</arm_group_label>
    <other_name>Aleve</other_name>
    <other_name>Anaprox</other_name>
    <other_name>Antalgin</other_name>
    <other_name>Feminax Ultra</other_name>
    <other_name>Flanax</other_name>
    <other_name>Inza</other_name>
    <other_name>Midol Extended Relief</other_name>
    <other_name>Nalgesin</other_name>
    <other_name>Naposin</other_name>
    <other_name>Naprelan</other_name>
    <other_name>Naprogesic</other_name>
    <other_name>Naprosyn</other_name>
    <other_name>Narocin</other_name>
    <other_name>Proxen</other_name>
    <other_name>Soproxen</other_name>
    <other_name>Synflex</other_name>
    <other_name>Xenobid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omeprazole</intervention_name>
    <description>Subjects enrolled in the active treatment arm will receive 20mg of Omeprazole prescribed twice daily, once in the morning and evening. Furthermore, subjects should take this one hour before a meal.</description>
    <arm_group_label>Active Treatment Intervention</arm_group_label>
    <other_name>Prilosec</other_name>
    <other_name>Iosepine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Subjects enrolled in the inactive treatment arm will receive two prescriptions, however, there are no active ingredients and are intended to look identical to the active treatment. Therefore, subjects will be instructed exactly the same way as if they were ingesting the active treatment.</description>
    <arm_group_label>Placebo Treatment Intervention</arm_group_label>
    <other_name>Sugar Pill</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  History of low back pain for a minimum of 6 months with or without signs and symptoms&#xD;
             of radiculopathy&#xD;
&#xD;
          -  Male or female, between the ages of 18 and 75 years, with no racial or ethnic&#xD;
             restrictions&#xD;
&#xD;
          -  Must have a Visual Analog Scale (VAS) pain score of 5 mm (of 10 mm maximum) at the&#xD;
             screening visit (for which 0mm = no pain, and 10 mm = worst pain imaginable);&#xD;
&#xD;
          -  Must be able to read and speak English and be willing to read and understand&#xD;
             instructions as well as questionnaires;&#xD;
&#xD;
          -  Must be in generally stable health;&#xD;
&#xD;
          -  Must sign an informed consent document after a complete explanation of the study&#xD;
             documenting that they understand the purpose of the study, procedures to be&#xD;
             undertaken, possible benefits, potential risks, and are willing to participate&#xD;
&#xD;
          -  Must have, on average, 5/10 units (VAS scale) of pain over the course of a two-week&#xD;
             period prior to visit 1; rounding up from 4.5/10 is permissible.&#xD;
&#xD;
          -  Must be willing to complete daily smart phone/computer app ratings.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Low back pain associated with any systemic signs or symptoms, e.g., fever, chills;&#xD;
&#xD;
          -  Evidence of rheumatoid arthritis, ankylosing spondylitis, acute vertebral fractures,&#xD;
             fibromyalgia, history of tumor in the back;&#xD;
&#xD;
          -  Other comorbid chronic pain or neurological conditions;&#xD;
&#xD;
          -  Involvement in litigation regarding their back pain or having a disability claim or&#xD;
             receiving workman's compensation or seeking either as a result of their low back pain;&#xD;
&#xD;
          -  Diagnosis of current depression or psychiatric disorder requiring treatment, or such a&#xD;
             diagnosis in the previous 6 months;&#xD;
&#xD;
          -  Beck Depression Inventory (BDI) Ia score greater or equal to 19 for two consecutive&#xD;
             completions; if the first score meets this criteria, the participant must be re-tested&#xD;
             before his/her next visit, but if the second score does not meet this criteria, the&#xD;
             participant will be included and followed closely throughout the study&#xD;
&#xD;
          -  Use of therapeutic doses of antidepressant medications (i.e., tricyclic depressants,&#xD;
             SSRIs, SNRIs; low doses used for sleep may be allowed);&#xD;
&#xD;
          -  Significant other medical disease such as unstable diabetes mellitus, congestive heart&#xD;
             failure, coronary or peripheral vascular disease, chronic obstructive lung disease, or&#xD;
             malignancy;&#xD;
&#xD;
          -  History of gastrointestinal ulcer during the past year;&#xD;
&#xD;
          -  History of myocardial infarction in the past year;&#xD;
&#xD;
          -  Uncontrolled hypertension;&#xD;
&#xD;
          -  Renal insufficiency;&#xD;
&#xD;
          -  Allergic to, or non-tolerant of, NSAIDs;&#xD;
&#xD;
          -  History of aspirin-sensitive asthma;&#xD;
&#xD;
          -  Current use of recreational drugs or history of alcohol or drug abuse;&#xD;
&#xD;
          -  Any change in medication for back pain in the last 30 days only applicable for visit 1&#xD;
&#xD;
          -  High dose opioid prophylaxis, as defined as &gt; 50mg morphine equivalent/day;&#xD;
&#xD;
          -  Any medical condition that in the investigator's judgment may prevent the individual&#xD;
             from completing the study or put the individual at undue risk;&#xD;
&#xD;
          -  In the judgment of the investigator, unable or unwilling to follow protocol and&#xD;
             instructions;&#xD;
&#xD;
          -  Evidence of poor treatment compliance, in the judgment of the investigator;&#xD;
&#xD;
          -  Intra-axial implants (e.g. spinal cord stimulators or pumps);&#xD;
&#xD;
          -  All exclusion criteria for MR safety: any metallic implants, brain or skull&#xD;
             abnormalities, tattoos on large body parts, and claustrophobia;&#xD;
&#xD;
          -  Pregnancy, or inability to use an effective form of contraception in women of&#xD;
             child-bearing age;&#xD;
&#xD;
          -  Diabetes (Type I or Type II);&#xD;
&#xD;
          -  Lactose intolerance or sensitivity to lactose&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Apkar V Apkarian, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northwestern University Feinberg School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Northwestern University Feinberg School of Medicine</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>December 6, 2016</study_first_submitted>
  <study_first_submitted_qc>December 7, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 8, 2016</study_first_posted>
  <results_first_submitted>May 16, 2019</results_first_submitted>
  <results_first_submitted_qc>October 12, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">November 7, 2022</results_first_posted>
  <last_update_submitted>October 12, 2022</last_update_submitted>
  <last_update_submitted_qc>October 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Northwestern University</investigator_affiliation>
    <investigator_full_name>Apkar Apkarian</investigator_full_name>
    <investigator_title>Professor in Physiology, Anesthesiology and Physical Medicine and Rehabilitation</investigator_title>
  </responsible_party>
  <keyword>chronic</keyword>
  <keyword>low back</keyword>
  <keyword>back</keyword>
  <keyword>pain</keyword>
  <keyword>brain</keyword>
  <keyword>MRI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Back Pain</mesh_term>
    <mesh_term>Low Back Pain</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Naproxen</mesh_term>
    <mesh_term>Omeprazole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 29, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT02986334/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>No Treatment Intervention</title>
          <description>Observational Subjects randomized to this arm will be asked to discontinue their current pain medications for the length of the study. This arm is not blinded, as both study staff and participants will be aware that they are not receiving a study treatment.</description>
        </group>
        <group group_id="P2">
          <title>Active Treatment Intervention</title>
          <description>Naproxen &amp; Omeprazole Subjects randomized to this arm will be asked to discontinue their current pain medications and take one 500mg naproxen capsule and one 40mg omeprazole capsule twice a day for the length of the study. This arm is double-blind, as neither participants nor study staff will know what medication the participants is receiving (blind to active versus placebo treatment).&#xD;
Naproxen: Subjects enrolled in the active treatment arm will receive 500mg of Naproxen prescribed twice daily, once in the morning and evening.&#xD;
Omeprazole: Subjects enrolled in the active treatment arm will receive 20mg of Omeprazole prescribed twice daily, once in the morning and evening. Furthermore, subjects should take this one hour before a meal.</description>
        </group>
        <group group_id="P3">
          <title>Placebo Treatment Intervention</title>
          <description>Subjects randomized to this arm will be asked to discontinue their current pain medications and take two placebo capsules twice a day for the length of the study. This arm is double-blind, as neither participants nor study staff will know what medication the participants is receiving (blind to active versus placebo treatment)&#xD;
Placebo: Subjects enrolled in the inactive treatment arm will receive two prescriptions, however, there are no active ingredients and are intended to look identical to the active treatment. Therefore, subjects will be instructed exactly the same way as if they were ingesting the active treatment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="40"/>
                <participants group_id="P3" count="40"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="33"/>
                <participants group_id="P3" count="33"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>non compliance in phone ratings</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>undisclosed comorbidities</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>No Treatment Intervention</title>
          <description>Observational Subjects randomized to this arm will be asked to discontinue their current pain medications for the length of the study. This arm is not blinded, as both study staff and participants will be aware that they are not receiving a study treatment.</description>
        </group>
        <group group_id="B2">
          <title>Active Treatment Intervention</title>
          <description>Naproxen &amp; Omeprazole Subjects randomized to this arm will be asked to discontinue their current pain medications and take one 500mg naproxen capsule and one 40mg omeprazole capsule twice a day for the length of the study. This arm is double-blind, as neither participants nor study staff will know what medication the participants is receiving (blind to active versus placebo treatment).&#xD;
Naproxen: Subjects enrolled in the active treatment arm will receive 500mg of Naproxen prescribed twice daily, once in the morning and evening.&#xD;
Omeprazole: Subjects enrolled in the active treatment arm will receive 20mg of Omeprazole prescribed twice daily, once in the morning and evening. Furthermore, subjects should take this one hour before a meal.</description>
        </group>
        <group group_id="B3">
          <title>Placebo Treatment Intervention</title>
          <description>Subjects randomized to this arm will be asked to discontinue their current pain medications and take two placebo capsules twice a day for the length of the study. This arm is double-blind, as neither participants nor study staff will know what medication the participants is receiving (blind to active versus placebo treatment)&#xD;
Placebo: Subjects enrolled in the inactive treatment arm will receive two prescriptions, however, there are no active ingredients and are intended to look identical to the active treatment. Therefore, subjects will be instructed exactly the same way as if they were ingesting the active treatment.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="14"/>
            <count group_id="B2" value="40"/>
            <count group_id="B3" value="40"/>
            <count group_id="B4" value="94"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="33"/>
                    <measurement group_id="B4" value="75"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.6" spread="11.6"/>
                    <measurement group_id="B2" value="58.0" spread="10.5"/>
                    <measurement group_id="B3" value="53.0" spread="14.3"/>
                    <measurement group_id="B4" value="55.8" spread="12.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="17"/>
                    <measurement group_id="B4" value="49"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="23"/>
                    <measurement group_id="B4" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="56"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="40"/>
                    <measurement group_id="B3" value="40"/>
                    <measurement group_id="B4" value="94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Change in Pain Assessed by Visual Analogue Scale (VAS)</title>
        <description>Self-report pain using a VAS scale (0-10) : 0 represents no pain and 10 the worst imaginable pain.&#xD;
Results are presented as percentage (%) change in pain before and after the intervention (baseline and post-intervention, 12 weeks).&#xD;
Percentage change is calculated with post-intervention pain minus baseline pain, divided by baseline pain i.e. (post - baseline) / baseline.</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>No Treatment Intervention</title>
            <description>Observational Subjects randomized to this arm will be asked to discontinue their current pain medications for the length of the study. This arm is not blinded, as both study staff and participants will be aware that they are not receiving a study treatment.</description>
          </group>
          <group group_id="O2">
            <title>Active Treatment Intervention</title>
            <description>Naproxen &amp; Omeprazole Subjects randomized to this arm will be asked to discontinue their current pain medications and take one 500mg naproxen capsule and one 40mg omeprazole capsule twice a day for the length of the study. This arm is double-blind, as neither participants nor study staff will know what medication the participants is receiving (blind to active versus placebo treatment).&#xD;
Naproxen: Subjects enrolled in the active treatment arm will receive 500mg of Naproxen prescribed twice daily, once in the morning and evening.&#xD;
Omeprazole: Subjects enrolled in the active treatment arm will receive 20mg of Omeprazole prescribed twice daily, once in the morning and evening. Furthermore, subjects should take this one hour before a meal.</description>
          </group>
          <group group_id="O3">
            <title>Placebo Treatment Intervention</title>
            <description>Subjects randomized to this arm will be asked to discontinue their current pain medications and take two placebo capsules twice a day for the length of the study. This arm is double-blind, as neither participants nor study staff will know what medication the participants is receiving (blind to active versus placebo treatment)&#xD;
Placebo: Subjects enrolled in the inactive treatment arm will receive two prescriptions, however, there are no active ingredients and are intended to look identical to the active treatment. Therefore, subjects will be instructed exactly the same way as if they were ingesting the active treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Pain Assessed by Visual Analogue Scale (VAS)</title>
          <description>Self-report pain using a VAS scale (0-10) : 0 represents no pain and 10 the worst imaginable pain.&#xD;
Results are presented as percentage (%) change in pain before and after the intervention (baseline and post-intervention, 12 weeks).&#xD;
Percentage change is calculated with post-intervention pain minus baseline pain, divided by baseline pain i.e. (post - baseline) / baseline.</description>
          <units>percentage of pain change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="33"/>
                <count group_id="O3" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0145" spread="0.036"/>
                    <measurement group_id="O2" value="-0.2082" spread="0.048"/>
                    <measurement group_id="O3" value="-0.1109" spread="0.050"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 weeks</time_frame>
      <desc>collected at each one of the 6 visits</desc>
      <group_list>
        <group group_id="E1">
          <title>No Treatment Intervention</title>
          <description>Observational Subjects randomized to this arm will be asked to discontinue their current pain medications for the length of the study. This arm is not blinded, as both study staff and participants will be aware that they are not receiving a study treatment.</description>
        </group>
        <group group_id="E2">
          <title>Active Treatment Intervention</title>
          <description>Naproxen &amp; Omeprazole Subjects randomized to this arm will be asked to discontinue their current pain medications and take one 500mg naproxen capsule and one 40mg omeprazole capsule twice a day for the length of the study. This arm is double-blind, as neither participants nor study staff will know what medication the participants is receiving (blind to active versus placebo treatment).&#xD;
Naproxen: Subjects enrolled in the active treatment arm will receive 500mg of Naproxen prescribed twice daily, once in the morning and evening.&#xD;
Omeprazole: Subjects enrolled in the active treatment arm will receive 20mg of Omeprazole prescribed twice daily, once in the morning and evening. Furthermore, subjects should take this one hour before a meal.</description>
        </group>
        <group group_id="E3">
          <title>Placebo Treatment Intervention</title>
          <description>Subjects randomized to this arm will be asked to discontinue their current pain medications and take two placebo capsules twice a day for the length of the study. This arm is double-blind, as neither participants nor study staff will know what medication the participants is receiving (blind to active versus placebo treatment)&#xD;
Placebo: Subjects enrolled in the inactive treatment arm will receive two prescriptions, however, there are no active ingredients and are intended to look identical to the active treatment. Therefore, subjects will be instructed exactly the same way as if they were ingesting the active treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="20" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataracts</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>GI issues</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Flu</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>upset stomach</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Cystourethroscopy Procedure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Tooth Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Seasonal allergies</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>pain following injection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Cortisone Shot in Right Hip</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Cold</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>High blood pressure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Puncture Bruising</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Molar tooth extraction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Appetite Loss</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Cyst removal in left arm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Right Latissimi dorsi Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Acute infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>pre-diabetic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Cervical Cancer screening</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Hip pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Acute pain in left latissimus dorsi</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Left shoulder pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Kidney Stones</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="40"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>human papillomavirus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Shortness of Breath</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Body Aches</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="40"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="40"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This study has several limitations including:&#xD;
The biosignature was poor predictability of individual participants' magnitude of pain relief, e&#xD;
The univariate analyses suggest that some features of the model could be further optimized</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Apkar Vania Apkarian</name_or_title>
      <organization>Northwestern University</organization>
      <phone>312-503-0404</phone>
      <email>a-apkarian@northwestern.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02986334
org study id: STU00080585 (Phase 2)
secondary id: 5R01AT007987-03
nct id: NCT02986334
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This study is designed to examine brain properties for placebo response in chronic back pain
      patients. The investigators have preliminary data indicating that, in blinded clinical trial
      studies with neutral instructions regarding treatment, chronic back pain (CBP) patients can
      be subdivided into placebo responders and non-responders, and these differences are
      PREDICTABLE a priori, by brain activity. The results imply that CBP placebo may have clinical
      utility and that its properties can be studied by human brain imaging techniques. In Phase I
      of the study, the investigators seek to identify brain imaging parameters that predict the
      propensity for the placebo response in an independent CBP cohort. In Phase II, the
      investigators will evaluate the interaction between placebo response and medication treatment
      in individuals stratified as placebo responders versus non-responders. This research is
      designed to critically assess the neurobiology of placebo analgesia for chronic pain in a
      partially-blind clinical trial.
Visit 1 (week -3): Screening visit (90 min):

      Participants will be evaluated with inclusion/exclusion criteria and complete the informed
      consent documents. A medical/pain history will be taken and physical exam will be completed
      by a physician and participants will be asked to rate their current back pain intensity.
      Participants will complete a set of 10 questionnaires that will ask about health and medical
      history, past and current pain levels, personality, and emotions. Participants will be
      allowed to take breaks and walk around during this time so that participants don't get tired
      while filling out questionnaires. Finally, participants will have blood drawn for screening
      purposes including to see if kidneys and liver are functioning as they should (the
      investigators will take 40 mL or about 8 teaspoons). Participants will be asked to return in
      2 weeks for baseline magnetic resonance imaging (MRI) scans. Participants will be asked to
      discontinue current pain medications 14 days prior to Visit 2 and take only the rescue
      medication ("rescue" medication that is also known as acetaminophen/Tylenol ®), given for
      pain during this time (see below) - this is so that the investigators can assess baseline
      amount of pain. Participants will be informed that they may be randomized in the placebo
      group and/or the no-treatment group (Visit 3) once one qualifies to continue in the study.
      Participants must, therefore,a be willing and able to stop taking the medication for pain for
      up to a maximum of 12 weeks during this study. Participants will be given acetaminophen (500
      mg, up to 4 times per day) to take for pain relief (as rescue medication), a dose that can be
      continued throughout the study. Participants are free to stop participation at any point in
      the study. Participants randomized into the treatment arm may receive the anti-inflammatory
      drug naproxen, since it is known to increase the risk of stomach and intestinal side effects,
      a combined naproxen/esomeprazole drug regimen will be given to participants to provide some
      protection for these types of side effects.

      Visit 2 (week -1): Baseline Scan (90 min):

      Participants will rate their pain intensity, complete questionnaires, and undergo brain
      scanning (anatomical and functional scans). Participants will receive medication, which can
      be used if the pain becomes too much to handle (500 mg four times per day maximum). The
      researcher will ask participants about how often participants used the "rescue" medication
      and any changes in health they may have experienced since the last visit.

      Visit 3 (week 0): Start of Treatment Period and Randomization (30-45 min):

      Participants will rate their pain intensity and complete questionnaires. Participants will be
      randomized into either a drug (placebo or naproxen and esomeprazole) treatment group or no
      treatment group; if participants are assigned to a treatment group (active or placebo),
      neither participants nor the clinical coordinator/assistant will know which group
      participants are allocated in. Enough medication will be given to participants to last until
      the next visit. The placebo group will receive two placebo capsules twice daily and the
      active drug group will receive one naproxen capsule (500mg) and one esomeprazole capsule
      (20mg) twice daily (morning and night) for the treatment period. The medication (Naproxen or
      Placebo) needs to be taken with at least one full glass (8 oz) of water and the other
      medication (Esomeprazole or Placebo) should be taken one hour before a meal. The researcher
      will provide the study medication; if participants were randomized into the no treatment
      group, participants will only receive rescue medication. The researcher will ask participants
      about how often participants used the "rescue" medication and any side effects participants
      experienced since Visit 2 took place. Additional "rescue" medication will be given.

      Visit 4 (week 3): Continuing Assessment (30-45 min). The procedures described for Visit 3
      will be repeated during this visit. The researcher will ask participants about how often they
      used the "rescue" medication and any side effects experienced since Visit 3 took place. As
      well, the researcher will ask how often participants took the study medication (if in a
      treatment group) and document the total pills ingested.

      Visit 5 (week 6): End of Treatment/Start of Washout and Final Scan (60-90 min):

      The procedures described for Visit 2 will be repeated during this visit. The researcher will
      ask participants about how often and reliably participants took the medication (if in a
      treatment group), as well as how often they used the "rescue" medication and any side effects
      experienced since Visit 4 took place. Participants will only receive the "rescue" medication
      for the upcoming 3 weeks.

      Visit 6 (week 9): Final Visit/End of Washout (30-45 min):

      Participants will return to complete questionnaires, but no brain scans will be done. The
      researcher will ask participants about how often they used the "rescue" medication and any
      side effects experienced since Visit 5 took place. If participants are in one of the
      treatment groups, participants will be asked to return all of the study medication and rescue
      medication at this time, and all treatment will be stopped at this visit.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percent Change in Pain Assessed by Visual Analogue Scale (VAS)
time frame: 12 weeks
description: Self-report pain using a VAS scale (0-10) : 0 represents no pain and 10 the worst imaginable pain.
Results are presented as percentage (%) change in pain before and after the intervention (baseline and post-intervention, 12 weeks).
Percentage change is calculated with post-intervention pain minus baseline pain, divided by baseline pain i.e. (post - baseline) / baseline.
arm group label: No Treatment Intervention
arm group type: No Intervention
description: Observational Subjects randomized to this arm will be asked to discontinue their current pain medications for the length of the study. This arm is not blinded, as both study staff and participants will be aware that they are not receiving a study treatment.
arm group label: Active Treatment Intervention
arm group type: Active Comparator
description: Naproxen & Omeprazole Subjects randomized to this arm will be asked to discontinue their current pain medications and take one 500mg naproxen capsule and one 40mg omeprazole capsule twice a day for the length of the study. This arm is double-blind, as neither participants nor study staff will know what medication the participants is receiving (blind to active versus placebo treatment).
arm group label: Placebo Treatment Intervention
arm group type: Placebo Comparator
description: Subjects randomized to this arm will be asked to discontinue their current pain medications and take two placebo capsules twice a day for the length of the study. This arm is double-blind, as neither participants nor study staff will know what medication the participants is receiving (blind to active versus placebo treatment)
intervention type: Drug
intervention name: Naproxen
description: Subjects enrolled in the active treatment arm will receive 500mg of Naproxen prescribed twice daily, once in the morning and evening.
arm group label: Active Treatment Intervention
other name: Aleve
other name: Anaprox
other name: Antalgin
other name: Feminax Ultra
other name: Flanax
other name: Inza
other name: Midol Extended Relief
other name: Nalgesin
other name: Naposin
other name: Naprelan
other name: Naprogesic
other name: Naprosyn
other name: Narocin
other name: Proxen
other name: Soproxen
other name: Synflex
other name: Xenobid
intervention type: Drug
intervention name: Omeprazole
description: Subjects enrolled in the active treatment arm will receive 20mg of Omeprazole prescribed twice daily, once in the morning and evening. Furthermore, subjects should take this one hour before a meal.
arm group label: Active Treatment Intervention
other name: Prilosec
other name: Iosepine
intervention type: Drug
intervention name: Placebo
description: Subjects enrolled in the inactive treatment arm will receive two prescriptions, however, there are no active ingredients and are intended to look identical to the active treatment. Therefore, subjects will be instructed exactly the same way as if they were ingesting the active treatment.
arm group label: Placebo Treatment Intervention
other name: Sugar Pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Apkar V Apkarian, PhD
role: Principal Investigator
affiliation: Northwestern University Feinberg School of Medicine
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Northwestern University
investigator full name: Apkar Apkarian
investigator title: Professor in Physiology, Anesthesiology and Physical Medicine and Rehabilitation
mesh term: Back Pain
mesh term: Low Back Pain
mesh term: Naproxen
mesh term: Omeprazole
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This study has several limitations including:
The biosignature was poor predictability of individual participants' magnitude of pain relief, e
The univariate analyses suggest that some features of the model could be further optimized
point of contact: 