<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/NCT03006393</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00087941</org_study_id>
    <secondary_id>R01MH108605</secondary_id>
    <nct_id>NCT03006393</nct_id>
  </id_info>
  <brief_title>Dynamics of Inflammation and Its Blockade on Motivational Circuitry in Depression</brief_title>
  <official_title>Dynamics of Inflammation and Its Blockade on Motivational Circuitry in Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to examine the effects of infliximab on measures related to&#xD;
      depression symptoms. Infliximab is also known by its brand name Remicade. Infliximab, or&#xD;
      Remicade, is given to by an intravenous (IV) needle and is currently used to treat rheumatoid&#xD;
      arthritis and Crohn's disease. Infliximab is thought to help these conditions because it&#xD;
      reduces inflammation in the body. Infliximab (Remicade) reduces inflammation by blocking a&#xD;
      chemical in the body called tumor necrosis factor (TNF)-alpha. This chemical produces&#xD;
      inflammation. Inflammatory chemicals in the body like TNF-alpha appear to be increased in&#xD;
      some people with major depression. Researchers believe that a drug like infliximab, which&#xD;
      blocks TNF-alpha, may be helpful in treating depression.&#xD;
&#xD;
      This is a double-blind, placebo-controlled study in which participants will be randomized to&#xD;
      receive one infusion of infliximab or placebo. The study will assess neuroimaging measures of&#xD;
      corticostriatal circuitry before and after a placebo-controlled pharmacologic blockade of&#xD;
      inflammation in 80 depressed patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The main purpose of this study is to examine the effects of infliximab on measures related to&#xD;
      depression symptoms. Infliximab is also known by its brand name Remicade. Infliximab, or&#xD;
      Remicade, is given by an intravenous (IV) needle and is currently used to treat rheumatoid&#xD;
      arthritis and Crohn's disease. Infliximab is thought to help these conditions because it&#xD;
      reduces inflammation in the body. Infliximab (Remicade) reduces inflammation by blocking a&#xD;
      chemical in the body called tumor necrosis factor (TNF)-alpha. This chemical produces&#xD;
      inflammation. Inflammatory chemicals in the body like TNF-alpha appear to be increased in&#xD;
      some people with major depression. Researchers believe that a drug like infliximab, which&#xD;
      blocks TNF-alpha, may be helpful in treating depression.&#xD;
&#xD;
      This is a double-blind, placebo-controlled study in which participants will be randomized to&#xD;
      receive one infusion of infliximab or placebo. This study will assess neuroimaging measures&#xD;
      of corticostriatal circuitry before and after a placebo-controlled pharmacologic blockade of&#xD;
      inflammation in 80 depressed patients (n = 40 per group) recruited to ensure high levels of&#xD;
      peripheral inflammation (CRP &gt; 3mg/L).&#xD;
&#xD;
      Primary aims are to evaluate whether 1) corticostriatal function during reward motivation and&#xD;
      anticipation are associated with change in peripheral inflammation following pharmacologic&#xD;
      blockade relative to placebo 2) the temporal dynamics of change in inflammation, gene-&#xD;
      expression, reward motivation and reinforcement learning behavior and motivational symptoms&#xD;
      assessed at baseline, and 24 hours, 3 days, 1 week and two weeks post infliximab infusion,&#xD;
      and 3) test an integrative multi- level path model to determine whether change in&#xD;
      corticostriatal circuitry following inflammation blockade mediates the relationship between&#xD;
      change in inflammation and change in motivational anhedonia symptoms.&#xD;
&#xD;
      These data will provide further validation of inflammatory cytokines as therapeutic targets&#xD;
      for motivational symptoms in depression and will define symptom targets and biomarkers of&#xD;
      response for future studies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2016</start_date>
  <completion_date type="Actual">September 26, 2020</completion_date>
  <primary_completion_date type="Actual">September 26, 2020</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>Effort-based Decision-making (EBDM) Task Score</measure>
    <time_frame>Baseline, Day 14</time_frame>
    <description>Reward motivation was assessed by a laboratory effort-based decision-making (EBDM) task. On each trial, participants make a choice about expending more or less physical effort (rapid button pressing) in exchange for varying amounts of monetary rewards. Models of subjective value were fit to each participants' data using maximum likelihood estimation and were compared using Bayesian Information Criterion to identify the model that provides the best fit for participants' responses. Discounting functions were based on previous work and include linear, quadratic, hyperbolic, flexible power models. Models considering the potential effects of fatigue and examination of post-scan switching behavior were also evaluated. The best-fitting model from baseline data was applied to look at changes related to infliximab. Reported values reflect a model-derived summary statistic for effort discounting behavior, without a fixed range, where lower values associated with greater motivation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma C-reactive Protein (CRP) Level</measure>
    <time_frame>Baseline, Day 14</time_frame>
    <description>C-reactive protein (CRP) is a blood test marker for inflammation in the body. CRP is produced in the liver and its level is measured by testing the blood. CRP level was measured at baseline and Day 14. Lower result correlates with better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Interleukin-6 (IL-6) Level</measure>
    <time_frame>Baseline, Day 14</time_frame>
    <description>Plasma IL-6 level will be collected via blood draw. IL-6 level was collected at baseline and Day 14. Lower result correlates with better outcome.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>Infliximab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to the infliximab group will receive one infusion of infliximab at 5mg/kg body weight.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants randomized to the placebo group will receive one placebo infusion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Infliximab</intervention_name>
    <description>One infusion of Infliximab (Remicade) will be administered intravenously (IV) at 5 mg/kg body weight over a two hour period.</description>
    <arm_group_label>Infliximab</arm_group_label>
    <other_name>Remicade</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>One infusion of placebo treatment will be administered intravenously (IV) over a two hour period.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Saline Solution</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All subjects will be fully ambulatory and in good medical health. Note: By Diagnostic&#xD;
             and Statistical Manual of Mental Disorders (DSM-4) definition of depression, subjects&#xD;
             will report impairment in ability to carry out daily activities as a result of their&#xD;
             major depression.&#xD;
&#xD;
          -  Subjects will be able to read and understand English.&#xD;
&#xD;
          -  Women must be postmenopausal (no menstrual period for a minimum of 1 year) or&#xD;
             surgically sterilized and/or have a negative serum pregnancy test within thirty days&#xD;
             of infusion (may be repeated closer to infusion date if deemed necessary by the PI or&#xD;
             PI's designee) and negative urine pregnancy tests throughout the study (performed at&#xD;
             each visit after the serum pregnancy test is completed).&#xD;
&#xD;
          -  Men and women of childbearing potential must use adequate birth control measures&#xD;
             (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with&#xD;
             spermicide, implantable or injectable contraceptives or surgical sterilization) for&#xD;
             the duration of the study and should continue such precautions for 6 months after&#xD;
             receiving the last infusion.&#xD;
&#xD;
        The following are considered eligible according to the following tuberculosis (TB)&#xD;
        screening criteria:&#xD;
&#xD;
          -  Have no history of latent or active TB prior to screening.&#xD;
&#xD;
          -  Have no signs or symptoms suggestive of active TB upon medical history and/or physical&#xD;
             examination.&#xD;
&#xD;
          -  Have had no recent close contact with a person with active TB or, if there has been&#xD;
             such contact, will be referred to a physician specializing in TB to undergo additional&#xD;
             evaluation to rule out infection. The candidate will be excluded from study&#xD;
             participation if the specialist diagnoses active TB and or determines TB treatment is&#xD;
             warranted.&#xD;
&#xD;
          -  Have a chest radiograph (both posterior-anterior and lateral views), taken within 3&#xD;
             months prior to the first administration of study agent and read by a qualified&#xD;
             radiologist, with no evidence of current active TB or old inactive TB.&#xD;
&#xD;
          -  History of negative purified protein derivative (PPD) test; or documentation of a&#xD;
             negative blood test (Quantiferon-TB-Gold). Any candidate testing positive for&#xD;
             tuberculosis in the medical screening evaluation, will be excluded from study&#xD;
             participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects will be excluded for any prior use of a TNF-alpha antagonist (i.e.&#xD;
             etanercept, infliximab, adalimumab) and/or use of any other immunosuppressant agent&#xD;
             (i.e. systemic corticosteroids or anti-proliferative agents such as methotrexate)&#xD;
             within one year of study entry.&#xD;
&#xD;
          -  Subjects chronically (i.e. more than one month) taking more than the equivalent of 2&#xD;
             mg of lorazepam a day of a benzodiazepine will be excluded.&#xD;
&#xD;
          -  Subjects will be required not to use anti-inflammatory agents, non-steroidal&#xD;
             anti-inflammatory agents (NSAIDs) (excluding 81mg of aspirin), glucocorticoid&#xD;
             containing medicines or statins, or cyclooxygenase-2 (COX-2) inhibitors during the&#xD;
             study as these agents may interfere with assessment of the relationship between&#xD;
             inflammatory markers and treatment response.&#xD;
&#xD;
        Note: Acetaminophen will be allowed.&#xD;
&#xD;
        Potential subjects will be excluded for a history of any of the following conditions:&#xD;
&#xD;
          -  Abnormal electrocardiogram&#xD;
&#xD;
          -  Auto-immune condition as confirmed by laboratory testing (i.e. rheumatoid arthritis,&#xD;
             inflammatory bowel disease, multiple sclerosis, lupus)&#xD;
&#xD;
          -  History of significant infectious sequelae, including but not limited to, abscess or&#xD;
             sepsis&#xD;
&#xD;
          -  Infection within one month prior to screening that required antibiotic or antiviral&#xD;
             therapy&#xD;
&#xD;
          -  History of a more than mild cognitive disorder or ≤ 24 on the Mini-Mental State Exam&#xD;
             (MMSE), unless otherwise approved by PI or his designee&#xD;
&#xD;
          -  Unstable cardiovascular or endocrinologic disease (as determined by physical&#xD;
             examination and/or laboratory testing)&#xD;
&#xD;
          -  Any other current or past medical condition that might increase the risk of&#xD;
             infliximab-related adverse events&#xD;
&#xD;
          -  Potential subjects will be excluded for any of the following conditions:&#xD;
&#xD;
          -  Active suicidal ideation defined as a score of ≥3 on Columbia Suicide Severity Rating&#xD;
             Scale (C-SSR).&#xD;
&#xD;
          -  Suicide attempt within six months of study entry&#xD;
&#xD;
          -  Schizophrenia or Schizoaffective Disorder&#xD;
&#xD;
          -  Active Eating Disorder (excluding binge-eating disorder)&#xD;
&#xD;
          -  History of any (non-mood related) psychotic disorder or active psychotic symptoms of&#xD;
             any type&#xD;
&#xD;
        Subjects will have had no infectious illnesses for one month prior to infusion. Should a&#xD;
        subject develop an infection (i.e. flu, upper respiratory viral infection) between&#xD;
        screening and infusion, the infusion will be delayed until 4 weeks after resolution of&#xD;
        symptoms. As noted above, patients with a chronic infectious condition or with a past&#xD;
        history of serious infectious complications will be excluded.&#xD;
&#xD;
        Subjects will be excluded for any evidence on laboratory testing (or by history) of&#xD;
        hematologic, renal or hepatic abnormality. Subjects will be excluded for a positive&#xD;
        anti-nuclear antibody (ANA) test.&#xD;
&#xD;
        Infliximab Related Exclusion Criteria:&#xD;
&#xD;
          -  Have had any previous treatment with monoclonal antibodies or antibody fragments.&#xD;
&#xD;
          -  History of receiving human/murine recombinant products or a known allergy to murine&#xD;
             products. A known allergy to murine product is definitely an exclusion criterion.&#xD;
&#xD;
          -  Documentation of seropositive for human immunodeficiency virus (HIV). Any candidate&#xD;
             testing positive for HIV, in the medical screening evaluation, will be excluded from&#xD;
             study participation.&#xD;
&#xD;
          -  Documentation of a positive test for hepatitis B surface antigen or hepatitis C. Any&#xD;
             candidate testing positive for hepatitis B or hepatitis C, in the medical screening&#xD;
             evaluation, will be excluded from study participation.&#xD;
&#xD;
          -  Are unable or unwilling to undergo multiple venipunctures because of poor tolerability&#xD;
             or lack of easy access.&#xD;
&#xD;
          -  Use of any investigational drug within 30 days prior to screening or within 5&#xD;
             half-lives of the investigational agent, whichever is longer.&#xD;
&#xD;
          -  Presence of a transplanted solid organ (with the exception of a corneal transplant &gt; 3&#xD;
             months prior to screening).&#xD;
&#xD;
          -  Have a concomitant diagnosis or history of congestive heart failure.&#xD;
&#xD;
          -  Have a history of alcohol or substance abuse within the preceding 6 months that, in&#xD;
             the opinion of the investigator, may increase the risks associated with study&#xD;
             participation or study agent administration, or may interfere with interpretation of&#xD;
             results. (As determined by Structured Clinical Interview for DSM-5 (SCID-5))&#xD;
&#xD;
          -  Have a known history of serious infections (e.g., hepatitis, pneumonia, or&#xD;
             pyelonephritis) in the previous 3 months.&#xD;
&#xD;
          -  Have or have had an opportunistic infection (e.g., herpes zoster [shingles],&#xD;
             cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria&#xD;
             other than TB) within 6 months prior to screening.&#xD;
&#xD;
          -  Have a history of lymphoproliferative disease, including lymphoma or signs suggestive&#xD;
             of possible lymphoproliferative disease such as lymphadenopathy of unusual size or&#xD;
             location (e.g., nodes in the posterior triangle of the neck, infraclavicular,&#xD;
             epitrochlear, or periaortic area), or splenomegaly.&#xD;
&#xD;
          -  Currently have any known malignancy other than the condition being treated or have a&#xD;
             history of malignancy within the previous 5 years, with the exception of basal cell or&#xD;
             squamous cell carcinoma of the skin that has been fully excised with no evidence of&#xD;
             recurrence.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Treadway, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>December 28, 2016</study_first_submitted>
  <study_first_submitted_qc>December 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 30, 2016</study_first_posted>
  <results_first_submitted>September 22, 2021</results_first_submitted>
  <results_first_submitted_qc>September 22, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">October 19, 2021</results_first_posted>
  <last_update_submitted>October 21, 2021</last_update_submitted>
  <last_update_submitted_qc>October 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 18, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Michael Treadway</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Neuroscience</keyword>
  <keyword>Behavioral</keyword>
  <keyword>Social</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammation</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infliximab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 6, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/93/NCT03006393/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 26, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/93/NCT03006393/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled at Emory University in Atlanta, Georgia, USA. Enrollment began in August 2016 and all follow up was complete by September 26, 2020.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Infliximab</title>
          <description>Participants randomized to the infliximab group received one infusion of Infliximab (Remicade) administered intravenously (IV) at 5 mg/kg body weight over a two hour period.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Participants randomized to the placebo group received one infusion of placebo treatment administered intravenously (IV) over a two hour period.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Pregnancy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Infliximab</title>
          <description>Participants randomized to the infliximab group received one infusion of Infliximab (Remicade) administered intravenously (IV) at 5 mg/kg body weight over a two hour period.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Participants randomized to the placebo group received one infusion of placebo treatment administered intravenously (IV) over a two hour period.</description>
        </group>
        <group group_id="B3">
          <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="21"/>
            <count group_id="B2" value="21"/>
            <count group_id="B3" value="42"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="40.1" spread="9.2"/>
                    <measurement group_id="B2" value="38.0" spread="7.9"/>
                    <measurement group_id="B3" value="39.03" spread="8.53"/>
                  </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="18"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="36"/>
                  </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="1"/>
                  </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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="21"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Effort-based Decision-making (EBDM) Task Score</title>
        <description>Reward motivation was assessed by a laboratory effort-based decision-making (EBDM) task. On each trial, participants make a choice about expending more or less physical effort (rapid button pressing) in exchange for varying amounts of monetary rewards. Models of subjective value were fit to each participants' data using maximum likelihood estimation and were compared using Bayesian Information Criterion to identify the model that provides the best fit for participants' responses. Discounting functions were based on previous work and include linear, quadratic, hyperbolic, flexible power models. Models considering the potential effects of fatigue and examination of post-scan switching behavior were also evaluated. The best-fitting model from baseline data was applied to look at changes related to infliximab. Reported values reflect a model-derived summary statistic for effort discounting behavior, without a fixed range, where lower values associated with greater motivation.</description>
        <time_frame>Baseline, Day 14</time_frame>
        <population>This analysis includes participants who completed the indicated study visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Infliximab</title>
            <description>Participants randomized to the infliximab group received one infusion of Infliximab (Remicade) administered intravenously (IV) at 5 mg/kg body weight over a two hour period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to the placebo group received one infusion of placebo treatment administered intravenously (IV) over a two hour period.</description>
          </group>
        </group_list>
        <measure>
          <title>Effort-based Decision-making (EBDM) Task Score</title>
          <description>Reward motivation was assessed by a laboratory effort-based decision-making (EBDM) task. On each trial, participants make a choice about expending more or less physical effort (rapid button pressing) in exchange for varying amounts of monetary rewards. Models of subjective value were fit to each participants' data using maximum likelihood estimation and were compared using Bayesian Information Criterion to identify the model that provides the best fit for participants' responses. Discounting functions were based on previous work and include linear, quadratic, hyperbolic, flexible power models. Models considering the potential effects of fatigue and examination of post-scan switching behavior were also evaluated. The best-fitting model from baseline data was applied to look at changes related to infliximab. Reported values reflect a model-derived summary statistic for effort discounting behavior, without a fixed range, where lower values associated with greater motivation.</description>
          <population>This analysis includes participants who completed the indicated study visit.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.13" spread="1.76"/>
                    <measurement group_id="O2" value="2.09" spread="1.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.85" spread="1.28"/>
                    <measurement group_id="O2" value="2.78" spread="1.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma C-reactive Protein (CRP) Level</title>
        <description>C-reactive protein (CRP) is a blood test marker for inflammation in the body. CRP is produced in the liver and its level is measured by testing the blood. CRP level was measured at baseline and Day 14. Lower result correlates with better outcome.</description>
        <time_frame>Baseline, Day 14</time_frame>
        <population>This analysis includes participants who completed the indicated study visit and had usable blood samples. Some participants did not complete the trial and another participant had a blood sample of poor quality.</population>
        <group_list>
          <group group_id="O1">
            <title>Infliximab</title>
            <description>Participants randomized to the infliximab group received one infusion of Infliximab (Remicade) administered intravenously (IV) at 5 mg/kg body weight over a two hour period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to the placebo group received one infusion of placebo treatment administered intravenously (IV) over a two hour period.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma C-reactive Protein (CRP) Level</title>
          <description>C-reactive protein (CRP) is a blood test marker for inflammation in the body. CRP is produced in the liver and its level is measured by testing the blood. CRP level was measured at baseline and Day 14. Lower result correlates with better outcome.</description>
          <population>This analysis includes participants who completed the indicated study visit and had usable blood samples. Some participants did not complete the trial and another participant had a blood sample of poor quality.</population>
          <units>mg/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.18" spread="3.28"/>
                    <measurement group_id="O2" value="7.81" spread="7.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.78" spread="4.63"/>
                    <measurement group_id="O2" value="6.35" spread="6.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma Interleukin-6 (IL-6) Level</title>
        <description>Plasma IL-6 level will be collected via blood draw. IL-6 level was collected at baseline and Day 14. Lower result correlates with better outcome.</description>
        <time_frame>Baseline, Day 14</time_frame>
        <population>This analysis includes participants who completed the indicated study visit and had usable blood samples. Some participants did not complete the trial and another participant had a blood sample of poor quality.</population>
        <group_list>
          <group group_id="O1">
            <title>Infliximab</title>
            <description>Participants randomized to the infliximab group received one infusion of Infliximab (Remicade) administered intravenously (IV) at 5 mg/kg body weight over a two hour period.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants randomized to the placebo group received one infusion of placebo treatment administered intravenously (IV) over a two hour period.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Interleukin-6 (IL-6) Level</title>
          <description>Plasma IL-6 level will be collected via blood draw. IL-6 level was collected at baseline and Day 14. Lower result correlates with better outcome.</description>
          <population>This analysis includes participants who completed the indicated study visit and had usable blood samples. Some participants did not complete the trial and another participant had a blood sample of poor quality.</population>
          <units>pg/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.13" spread="0.96"/>
                    <measurement group_id="O2" value="1.07" spread="0.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.97" spread="1.00"/>
                    <measurement group_id="O2" value="1.19" spread="1.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were tracked from the time of consent through the 30-Day Post-Infusion Follow-Up Phone Call.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Infliximab</title>
          <description>Participants randomized to the infliximab group received one infusion of Infliximab (Remicade) administered intravenously (IV) at 5 mg/kg body weight over a two hour period.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants randomized to the placebo group received one infusion of placebo treatment administered intravenously (IV) over a two hour period.</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="21"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="19" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Heartburn</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Bloody stool</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Stomach ache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="21"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Allergies</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Change in blood pressure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Motor vehicle accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Swelling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Change in appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in joints</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pain in leg</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Muscle tension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pain in neck</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Laceration</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Numbness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Migraine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Pregnancy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Change in urination</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Menstruation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Itchiness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Bruises</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="21"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>
    <point_of_contact>
      <name_or_title>Dr. Michael Treadway</name_or_title>
      <organization>Emory University</organization>
      <phone>(404) 727-3166</phone>
      <email>mtreadway@emory.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/NCT03006393
org study id: IRB00087941
secondary id: R01MH108605
nct id: NCT03006393
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The main purpose of this study is to examine the effects of infliximab on measures related to
      depression symptoms. Infliximab is also known by its brand name Remicade. Infliximab, or
      Remicade, is given to by an intravenous (IV) needle and is currently used to treat rheumatoid
      arthritis and Crohn's disease. Infliximab is thought to help these conditions because it
      reduces inflammation in the body. Infliximab (Remicade) reduces inflammation by blocking a
      chemical in the body called tumor necrosis factor (TNF)-alpha. This chemical produces
      inflammation. Inflammatory chemicals in the body like TNF-alpha appear to be increased in
      some people with major depression. Researchers believe that a drug like infliximab, which
      blocks TNF-alpha, may be helpful in treating depression.

      This is a double-blind, placebo-controlled study in which participants will be randomized to
      receive one infusion of infliximab or placebo. The study will assess neuroimaging measures of
      corticostriatal circuitry before and after a placebo-controlled pharmacologic blockade of
      inflammation in 80 depressed patients.
The main purpose of this study is to examine the effects of infliximab on measures related to
      depression symptoms. Infliximab is also known by its brand name Remicade. Infliximab, or
      Remicade, is given by an intravenous (IV) needle and is currently used to treat rheumatoid
      arthritis and Crohn's disease. Infliximab is thought to help these conditions because it
      reduces inflammation in the body. Infliximab (Remicade) reduces inflammation by blocking a
      chemical in the body called tumor necrosis factor (TNF)-alpha. This chemical produces
      inflammation. Inflammatory chemicals in the body like TNF-alpha appear to be increased in
      some people with major depression. Researchers believe that a drug like infliximab, which
      blocks TNF-alpha, may be helpful in treating depression.

      This is a double-blind, placebo-controlled study in which participants will be randomized to
      receive one infusion of infliximab or placebo. This study will assess neuroimaging measures
      of corticostriatal circuitry before and after a placebo-controlled pharmacologic blockade of
      inflammation in 80 depressed patients (n = 40 per group) recruited to ensure high levels of
      peripheral inflammation (CRP > 3mg/L).

      Primary aims are to evaluate whether 1) corticostriatal function during reward motivation and
      anticipation are associated with change in peripheral inflammation following pharmacologic
      blockade relative to placebo 2) the temporal dynamics of change in inflammation, gene-
      expression, reward motivation and reinforcement learning behavior and motivational symptoms
      assessed at baseline, and 24 hours, 3 days, 1 week and two weeks post infliximab infusion,
      and 3) test an integrative multi- level path model to determine whether change in
      corticostriatal circuitry following inflammation blockade mediates the relationship between
      change in inflammation and change in motivational anhedonia symptoms.

      These data will provide further validation of inflammatory cytokines as therapeutic targets
      for motivational symptoms in depression and will define symptom targets and biomarkers of
      response for future studies.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Effort-based Decision-making (EBDM) Task Score
time frame: Baseline, Day 14
description: Reward motivation was assessed by a laboratory effort-based decision-making (EBDM) task. On each trial, participants make a choice about expending more or less physical effort (rapid button pressing) in exchange for varying amounts of monetary rewards. Models of subjective value were fit to each participants' data using maximum likelihood estimation and were compared using Bayesian Information Criterion to identify the model that provides the best fit for participants' responses. Discounting functions were based on previous work and include linear, quadratic, hyperbolic, flexible power models. Models considering the potential effects of fatigue and examination of post-scan switching behavior were also evaluated. The best-fitting model from baseline data was applied to look at changes related to infliximab. Reported values reflect a model-derived summary statistic for effort discounting behavior, without a fixed range, where lower values associated with greater motivation.
measure: Plasma C-reactive Protein (CRP) Level
time frame: Baseline, Day 14
description: C-reactive protein (CRP) is a blood test marker for inflammation in the body. CRP is produced in the liver and its level is measured by testing the blood. CRP level was measured at baseline and Day 14. Lower result correlates with better outcome.
measure: Plasma Interleukin-6 (IL-6) Level
time frame: Baseline, Day 14
description: Plasma IL-6 level will be collected via blood draw. IL-6 level was collected at baseline and Day 14. Lower result correlates with better outcome.
arm group label: Infliximab
arm group type: Experimental
description: Participants randomized to the infliximab group will receive one infusion of infliximab at 5mg/kg body weight.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants randomized to the placebo group will receive one placebo infusion.
intervention type: Drug
intervention name: Infliximab
description: One infusion of Infliximab (Remicade) will be administered intravenously (IV) at 5 mg/kg body weight over a two hour period.
arm group label: Infliximab
other name: Remicade
intervention type: Other
intervention name: Placebo
description: One infusion of placebo treatment will be administered intravenously (IV) over a two hour period.
arm group label: Placebo
other name: Saline Solution
criteria: 
gender: All
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: No
last name: Michael Treadway, PhD
role: Principal Investigator
affiliation: Emory University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Michael Treadway
investigator title: Assistant Professor
mesh term: Inflammation
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Infliximab
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 