<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/NCT01725048</url>
  </required_header>
  <id_info>
    <org_study_id>LCCC 1021</org_study_id>
    <nct_id>NCT01725048</nct_id>
  </id_info>
  <brief_title>Pilot Study to Evaluate Individualized Choice of Antidepressants in Patients With Cancer</brief_title>
  <acronym>NRR</acronym>
  <official_title>A Pilot Study to Evaluate Individualized Choice of Antidepressant in Patients With Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>UNC Lineberger Comprehensive Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>UNC Lineberger Comprehensive Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study to test the hypothesis that the antidepressants mirtazapine and&#xD;
      citalopram are effective treatment for major depressive disorder (MDD) in cancer patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Major depressive disorder (MDD) is a debilitating illness associated with increased mortality&#xD;
      and significant impairment in quality of life. The prevalence of MDD is particularly high in&#xD;
      patients with cancer, as much as 38% in some studies.&#xD;
&#xD;
      The study of depression in cancer patients is particularly important, as these co-morbid&#xD;
      illnesses can frequently complicate the management of each other. In addition to affecting&#xD;
      quality of life, poorly controlled depression can affect cancer treatment adherence and can&#xD;
      lead to poor treatment outcomes.&#xD;
&#xD;
      Depression can be challenging to diagnose in patients with cancer. A spectrum of depressive&#xD;
      symptoms can be seen, ranging from appropriate sadness in response to a life threatening&#xD;
      diagnosis, to a major depressive episode. The diagnosis is confounded by the symptoms brought&#xD;
      on by the cancer and its treatment, such as fatigue, insomnia, anorexia, and pain.&#xD;
      Medications commonly used in cancer patients such as narcotics, benzodiazepines,&#xD;
      antihistamines, steroids, antibiotics, chemotherapy, and endocrine therapy can all lead to&#xD;
      side effects that further confuse the picture. However, while challenging, evidence does&#xD;
      suggest that a valid diagnosis of depression can be made in this patient population.&#xD;
&#xD;
      The current standard for diagnosing MDD is the Diagnostic and Statistical Manual of Mental&#xD;
      Disorders - Fourth Edition - Text Revision (DSM-IV-TR), which was published in 2000 by the&#xD;
      American Psychiatric Association. The diagnosis is made based on an interview between the&#xD;
      patient and physician in which nine criteria are assessed, including depressed mood,&#xD;
      anhedonia, weight loss or gain, insomnia or hypersomnia, psychomotor agitation or&#xD;
      retardation, fatigue, feelings of worthlessness or guilt, difficulty concentrating, and&#xD;
      recurrent thoughts of death. In patients with cancer, the diagnosis of MDD is more often&#xD;
      based on anhedonia and feelings of worthlessness, as depressed mood, weight fluctuation, and&#xD;
      sleep disturbance can be symptoms of the underlying cancer itself. Once the diagnosis has&#xD;
      been made, there are several tools which have been created and validated for the purpose of&#xD;
      assessing the severity of depression and for following the severity over time. The tool we&#xD;
      intend to use in this study is the PHQ-9.&#xD;
&#xD;
      Therapy for MDD in the general population includes both psychotherapy and pharmacological&#xD;
      intervention. However, the optimal therapy of MDD in cancer patients remains uncertain. Very&#xD;
      few placebo controlled trials have been performed in this population, and there is currently&#xD;
      no uniformly accepted standard of care. Some of the evidence from studies in depressed but&#xD;
      otherwise medically healthy patients may be applicable to cancer patients, but there are&#xD;
      several factors which complicate the treatment of depression in this group. For example, the&#xD;
      overlap of symptoms between depression and the underlying malignancy can confound the&#xD;
      diagnosis, as discussed earlier. Simultaneous treatment of the underlying malignancy&#xD;
      introduces adverse effects from surgery, chemotherapy, or radiation, as well as an increased&#xD;
      likelihood of drug-drug interactions. Finally, co-morbid conditions such as cancer pain can&#xD;
      contribute to the depression, requiring simultaneous therapy. As a result of these unique&#xD;
      factors, the treatment of MDD in cancer patients cannot necessarily be approached using the&#xD;
      standard recommendations for the general population.&#xD;
&#xD;
      There is scant evidence supporting the effectiveness of pharmacologic therapy in cancer&#xD;
      patients with MDD. In the last 25 years only four placebo controlled trials have been&#xD;
      published, and of these only two have shown a statistically significant improvement in&#xD;
      depression scores with active treatment.&#xD;
&#xD;
      Additional studies are needed to evaluate some of the newer antidepressants within the cancer&#xD;
      population and to assess whether this strategy of matching side effects to symptoms is&#xD;
      beneficial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2011</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">May 2012</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Feasibility</measure>
    <time_frame>One year</time_frame>
    <description>To determine the feasibility of this pilot study to recruit subjects, as measured by the number of individuals enrolled per month, such that the goal of the study is met in a timely manner.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Depression Score</measure>
    <time_frame>9 weeks</time_frame>
    <description>To assess the short-term (9 week) outcome of mirtazapine or citalopram in cancer patients with major depressive disorder based on mean improvement in depressive symptoms as measured by the Patient Health Questionnaire (PHQ-9)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Major Depressive Disorder</condition>
  <condition>Neoplasms</condition>
  <arm_group>
    <arm_group_label>Mirtazapine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Treatment with oral mirtazapine, dosed once daily, for 9 weeks, with starting dose of 7.5 milligrams (mg) daily up to 30mg daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Citalopram</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Treatment with Citalopram, once daily, for 9 weeks, with dosages starting at 10mg once daily to 40mg once daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mirtazapine</intervention_name>
    <description>7.5mg by mouth once a day at night. If subject has not had a 50% or greater reduction in the PHQ-9 depression assessment score, and if the subject is not experiencing unacceptable adverse effects, then the dose may be escalated first to 15mg by mouth every night and then to 30mg by mouth every night.</description>
    <arm_group_label>Mirtazapine</arm_group_label>
    <other_name>Remeron</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Citalopram</intervention_name>
    <description>Citalopram 10mg by mouth once daily. If the subject has not had a 50% or greater reduction in PHQ-9 depression assessment score, and if the subject is not experiencing unacceptable side effects, then the dose may be escalated first to 20mg by mouth every day and then to 40mg by mouth once a day.</description>
    <arm_group_label>Citalopram</arm_group_label>
    <other_name>Celexa</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with a malignancy&#xD;
&#xD;
          -  Informed consent obtained and signed&#xD;
&#xD;
          -  Greater than or equal to 18 years of age&#xD;
&#xD;
          -  Life expectancy determined to be greater than or equal to 6 months&#xD;
&#xD;
          -  Diagnosed with Major Depressive Disorder based on clinical examination and the&#xD;
             DSM-IV-TR criteria&#xD;
&#xD;
          -  PHQ-9 depression assessment completed by subject, with a score of 10 or greater&#xD;
&#xD;
          -  Able to take whole or crushed tablets by mouth or by feeding tube&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to complete self-report instruments due to illiteracy, neurologic illness,&#xD;
             visual problems, inability to speak or read English, or other causes&#xD;
&#xD;
          -  Treatment with antidepressants or antipsychotics within the last 3 months&#xD;
&#xD;
          -  Psychotic or manic behavior&#xD;
&#xD;
          -  Active suicidal ideation or plan&#xD;
&#xD;
          -  Current illicit substance abuse&#xD;
&#xD;
          -  Severe renal impairment as defined by creatinine clearance of &lt;15&#xD;
             milliliters/minute/1.73 meters squared (mL/min/m2)&#xD;
&#xD;
          -  Severe hepatic impairment as defined by Aspartate Aminotransferase (AST) or alanine&#xD;
             aminotransferase (ALT) &gt;5x the upper limit of normal, or a total bilirubin &gt; 3.0&#xD;
             milliliters/deciliter (mL/dL)&#xD;
&#xD;
          -  History of congenital long QT syndrome&#xD;
&#xD;
          -  Clinically significant congestive heart failure or bradyarrhythmias&#xD;
&#xD;
          -  Treatment with a concomitant medication that is known to have a strong association&#xD;
             with corrected QT interval (QTc) prolongation AND a QTc &gt;460 for men or &gt;470 for&#xD;
             women. Applicable to the citalopram arm only&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eliza Park, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of North Carolina Hospital</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.unclineberger.org</url>
    <description>Website for the University of North Carolina Lineberger Comprehensive Cancer Center</description>
  </link>
  <link>
    <url>http://www.cancer.gov</url>
    <description>Website for the National Cancer Institute</description>
  </link>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>November 7, 2012</study_first_submitted>
  <study_first_submitted_qc>November 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 12, 2012</study_first_posted>
  <last_update_submitted>March 8, 2017</last_update_submitted>
  <last_update_submitted_qc>March 8, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Major depressive disorder</keyword>
  <keyword>Neoplasms</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mirtazapine</mesh_term>
    <mesh_term>Citalopram</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01725048
org study id: LCCC 1021
nct id: NCT01725048
lead sponsor: 
has dmc: Yes
This is a pilot study to test the hypothesis that the antidepressants mirtazapine and
      citalopram are effective treatment for major depressive disorder (MDD) in cancer patients.
Major depressive disorder (MDD) is a debilitating illness associated with increased mortality
      and significant impairment in quality of life. The prevalence of MDD is particularly high in
      patients with cancer, as much as 38% in some studies.

      The study of depression in cancer patients is particularly important, as these co-morbid
      illnesses can frequently complicate the management of each other. In addition to affecting
      quality of life, poorly controlled depression can affect cancer treatment adherence and can
      lead to poor treatment outcomes.

      Depression can be challenging to diagnose in patients with cancer. A spectrum of depressive
      symptoms can be seen, ranging from appropriate sadness in response to a life threatening
      diagnosis, to a major depressive episode. The diagnosis is confounded by the symptoms brought
      on by the cancer and its treatment, such as fatigue, insomnia, anorexia, and pain.
      Medications commonly used in cancer patients such as narcotics, benzodiazepines,
      antihistamines, steroids, antibiotics, chemotherapy, and endocrine therapy can all lead to
      side effects that further confuse the picture. However, while challenging, evidence does
      suggest that a valid diagnosis of depression can be made in this patient population.

      The current standard for diagnosing MDD is the Diagnostic and Statistical Manual of Mental
      Disorders - Fourth Edition - Text Revision (DSM-IV-TR), which was published in 2000 by the
      American Psychiatric Association. The diagnosis is made based on an interview between the
      patient and physician in which nine criteria are assessed, including depressed mood,
      anhedonia, weight loss or gain, insomnia or hypersomnia, psychomotor agitation or
      retardation, fatigue, feelings of worthlessness or guilt, difficulty concentrating, and
      recurrent thoughts of death. In patients with cancer, the diagnosis of MDD is more often
      based on anhedonia and feelings of worthlessness, as depressed mood, weight fluctuation, and
      sleep disturbance can be symptoms of the underlying cancer itself. Once the diagnosis has
      been made, there are several tools which have been created and validated for the purpose of
      assessing the severity of depression and for following the severity over time. The tool we
      intend to use in this study is the PHQ-9.

      Therapy for MDD in the general population includes both psychotherapy and pharmacological
      intervention. However, the optimal therapy of MDD in cancer patients remains uncertain. Very
      few placebo controlled trials have been performed in this population, and there is currently
      no uniformly accepted standard of care. Some of the evidence from studies in depressed but
      otherwise medically healthy patients may be applicable to cancer patients, but there are
      several factors which complicate the treatment of depression in this group. For example, the
      overlap of symptoms between depression and the underlying malignancy can confound the
      diagnosis, as discussed earlier. Simultaneous treatment of the underlying malignancy
      introduces adverse effects from surgery, chemotherapy, or radiation, as well as an increased
      likelihood of drug-drug interactions. Finally, co-morbid conditions such as cancer pain can
      contribute to the depression, requiring simultaneous therapy. As a result of these unique
      factors, the treatment of MDD in cancer patients cannot necessarily be approached using the
      standard recommendations for the general population.

      There is scant evidence supporting the effectiveness of pharmacologic therapy in cancer
      patients with MDD. In the last 25 years only four placebo controlled trials have been
      published, and of these only two have shown a statistically significant improvement in
      depression scores with active treatment.

      Additional studies are needed to evaluate some of the newer antidepressants within the cancer
      population and to assess whether this strategy of matching side effects to symptoms is
      beneficial.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Feasibility
time frame: One year
description: To determine the feasibility of this pilot study to recruit subjects, as measured by the number of individuals enrolled per month, such that the goal of the study is met in a timely manner.
measure: Depression Score
time frame: 9 weeks
description: To assess the short-term (9 week) outcome of mirtazapine or citalopram in cancer patients with major depressive disorder based on mean improvement in depressive symptoms as measured by the Patient Health Questionnaire (PHQ-9)
arm group label: Mirtazapine
arm group type: Active Comparator
description: Treatment with oral mirtazapine, dosed once daily, for 9 weeks, with starting dose of 7.5 milligrams (mg) daily up to 30mg daily.
arm group label: Citalopram
arm group type: Active Comparator
description: Treatment with Citalopram, once daily, for 9 weeks, with dosages starting at 10mg once daily to 40mg once daily.
intervention type: Drug
intervention name: Mirtazapine
description: 7.5mg by mouth once a day at night. If subject has not had a 50% or greater reduction in the PHQ-9 depression assessment score, and if the subject is not experiencing unacceptable adverse effects, then the dose may be escalated first to 15mg by mouth every night and then to 30mg by mouth every night.
arm group label: Mirtazapine
other name: Remeron
intervention type: Drug
intervention name: Citalopram
description: Citalopram 10mg by mouth once daily. If the subject has not had a 50% or greater reduction in PHQ-9 depression assessment score, and if the subject is not experiencing unacceptable side effects, then the dose may be escalated first to 20mg by mouth every day and then to 40mg by mouth once a day.
arm group label: Citalopram
other name: Celexa
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Eliza Park, MD
role: Principal Investigator
affiliation: University of North Carolina
facility: 
country: United States
url: http://www.unclineberger.org
description: Website for the University of North Carolina Lineberger Comprehensive Cancer Center
url: http://www.cancer.gov
description: Website for the National Cancer Institute
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
mesh term: Mirtazapine
mesh term: Citalopram