<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/NCT02203552</url>
  </required_header>
  <id_info>
    <org_study_id>OSU-13165</org_study_id>
    <secondary_id>NCI-2014-00851</secondary_id>
    <nct_id>NCT02203552</nct_id>
  </id_info>
  <brief_title>Minocycline Hydrochloride in Reducing Chemotherapy Induced Depression and Anxiety in Patients With Stage I-III Breast Cancer</brief_title>
  <official_title>Randomized Placebo Controlled Study of Minocycline for Amelioration of Chemotherapy Induced Affective Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ohio State University Comprehensive Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ohio State University Comprehensive Cancer Center</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>
      This randomized clinical trial studies how well minocycline hydrochloride works in reducing&#xD;
      chemotherapy induced depression and anxiety in patients with stage I-III breast cancer.&#xD;
      Minocycline hydrochloride may prevent changes in memory and thinking and improve the quality&#xD;
      of life of breast cancer patients receiving chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate anxiety and depression in women with stages I-III breast cancer during the&#xD;
      first 8 weeks of doxorubicin-based adjuvant therapy randomized to receive either minocycline&#xD;
      (minocycline hydrochloride) or placebo.&#xD;
&#xD;
      II. To evaluate markers of neuro-inflammation as assessed by blood based inflammatory&#xD;
      cytokines and C11-choline positron emission tomography (PET) in women with stages I-III&#xD;
      breast cancer during the first 8 weeks of doxorubicin-based adjuvant therapy randomized to&#xD;
      receive either minocycline or placebo.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 2 arms.&#xD;
&#xD;
      ARM I: Beginning 1 week prior to chemotherapy, patients receive minocycline hydrochloride&#xD;
      orally (PO) twice daily (BID) for 9 weeks.&#xD;
&#xD;
      ARM II: Beginning 1 week prior to chemotherapy, patients receive placebo PO BID for 9 weeks.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for 6 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">June 23, 2015</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">June 25, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in Center for Epidemiological Studies Depression Scale (CES-D) scores</measure>
    <time_frame>Baseline to 9 weeks</time_frame>
    <description>The 95% confidence intervals of the depression change from baseline to the end of study and the difference between the treatment and placebo groups. The influences of covariate, such as disease stage and depression drug usage, will be considered in the mixed models as exploratory analyses.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in the State Trait Anxiety Index (STAI) scores</measure>
    <time_frame>Baseline to 9 weeks</time_frame>
    <description>The 95% confidence intervals of the anxiety change from baseline to the end of study and the difference between the treatment and placebo groups. The influences of covariate, such as disease stage and depression drug usage, will be considered in the mixed models as exploratory analyses.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Hamilton Anxiety Rating Scale scores</measure>
    <time_frame>Baseline to 9 weeks</time_frame>
    <description>The 95% confidence intervals of the anxiety change from baseline to the end of study and the difference between the treatment and placebo groups. The influences of covariate, such as disease stage and depression drug usage, will be considered in the mixed models as exploratory analyses. In addition, change overtime of all outcomes for each individual will be plotted to visually explore any patterns and to generate hypothesis to be tested in future studies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Hamilton Rating Scale for Depression scores</measure>
    <time_frame>Baseline to 9 weeks</time_frame>
    <description>The 95% confidence intervals of the depression change from baseline to the end of study and the difference between the treatment and placebo groups. The influences of covariate, such as disease stage and depression drug usage, will be considered in the mixed models as exploratory analyses. In addition, change overtime of all outcomes for each individual will be plotted to visually explore any patterns and to generate hypothesis to be tested in future studies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in inflammatory blood markers</measure>
    <time_frame>Baseline to 6 months</time_frame>
    <description>Scatter plots will be used to explore the pair-wise correlation among the changes of CES-D and STAI scores, blood biomarkers changes, and PET/MRI measures. A statistical model will be used to explore whether the blood based biomarkers and PET/MRI measures can be used to predict the changes in CES-D and STAI scores, which then could be used as potential surrogate markers in future studies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in the PET/MRI measures</measure>
    <time_frame>Baseline to 6 months</time_frame>
    <description>Scatter plots will be used to explore the pair-wise correlation among the changes of CES-D and STAI scores, blood biomarkers changes, and PET/MRI measures. A statistical model will be used to explore whether the blood based biomarkers and PET/MRI measures can be used to predict the changes in CES-D and STAI scores, which then could be used as potential surrogate markers in future studies.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Anxiety Disorder</condition>
  <condition>Depression</condition>
  <condition>Recurrent Breast Cancer</condition>
  <condition>Stage IA Breast Cancer</condition>
  <condition>Stage IB Breast Cancer</condition>
  <condition>Stage II Breast Cancer</condition>
  <condition>Stage IIIA Breast Cancer</condition>
  <condition>Stage IIIB Breast Cancer</condition>
  <condition>Stage IIIC Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Arm I (minocycline hydrochloride)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Beginning 1 week prior to chemotherapy, patients receive minocycline hydrochloride orally PO BID for 9 weeks. Laboratory biomarker analysis will also be obtained weekly on protocol. Questionnaire administration weekly.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (placebo)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Beginning 1 week prior to chemotherapy, patients receive placebo PO BID for 9 weeks. Laboratory biomarker analysis will also be obtained weekly on protocol. Questionnaire administration weekly.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>minocycline hydrochloride</intervention_name>
    <description>100 mg bid given by mouth for 9 weeks</description>
    <arm_group_label>Arm I (minocycline hydrochloride)</arm_group_label>
    <other_name>Dynacin</other_name>
    <other_name>Minocin</other_name>
    <other_name>Minomax</other_name>
    <other_name>Minomycin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Placebo given by mouth for 9 weeks</description>
    <arm_group_label>Arm II (placebo)</arm_group_label>
    <other_name>PLCB</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>laboratory biomarker analysis</intervention_name>
    <description>Correlative blood levels for cortisol, high sensitivity c-reactive protein (hs-CRP) and inflammatory factors including but not limited to IL-6, TNF-α, IL-1β, and MCP-1 will also be obtained weekly on protocol.</description>
    <arm_group_label>Arm I (minocycline hydrochloride)</arm_group_label>
    <arm_group_label>Arm II (placebo)</arm_group_label>
    <other_name>special studies</other_name>
    <other_name>Correlative studies</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire administration</intervention_name>
    <description>The CES-D and STAI will be administrated weekly.</description>
    <arm_group_label>Arm I (minocycline hydrochloride)</arm_group_label>
    <arm_group_label>Arm II (placebo)</arm_group_label>
    <other_name>Ancillary studies</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Women diagnosed with breast cancer stages I-III initiating first line adjuvant or&#xD;
             neoadjuvant doxorubicin hydrochloride (DOX) chemotherapy&#xD;
&#xD;
          -  Postmenopausal defined as amenorrhea &gt; 12 months or follicle stimulating hormone (FSH)&#xD;
             and estradiol in institutional postmenopausal range&#xD;
&#xD;
          -  Ability to understand English and read and write at the 8th grade level and give a&#xD;
             written informed consent document&#xD;
&#xD;
          -  For additional cohort, women with breast cancer stages I-III who currently on or&#xD;
             within 18 months of completing first line adjuvant or neoadjuvant DOX chemotherapy or&#xD;
             other chemotherapy for breast cancer.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Rheumatoid arthritis and other types of autoimmune and inflammatory joint disease,&#xD;
             with the exception of osteoarthritis and fibromyalgia&#xD;
&#xD;
          -  Concurrent other malignancy or metastatic malignancy of any kind&#xD;
&#xD;
          -  Reported diagnosis of major depression or anxiety disorder prior to breast cancer (BC)&#xD;
             diagnosis&#xD;
&#xD;
          -  Currently prescribed psychotropic medications including anti-depressants&#xD;
&#xD;
          -  Known bleeding disorders&#xD;
&#xD;
          -  History of diabetes mellitus, heart disease or stroke&#xD;
&#xD;
          -  Current use of warfarin or other anticoagulants&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, hypertension, or psychiatric illness/social situation that would limit&#xD;
             compliance with study requirements&#xD;
&#xD;
          -  Pregnant or nursing women&#xD;
&#xD;
          -  Concurrent use of daily full dose aspirin (&gt;= 325 mg/day), nonsteroidal&#xD;
             anti-inflammatory drugs (NSAIDs) or NSAID-containing products or steroids; one month&#xD;
             washout period is required prior to randomization&#xD;
&#xD;
          -  Unable to give informed consent&#xD;
&#xD;
          -  Tetracycline allergy&#xD;
&#xD;
          -  Any contraindication to magnetic resonance imaging (MRI)/PET examination including but&#xD;
             not limited to ferromagnetic metal in the body, pacemaker, or severe claustrophobia;&#xD;
             (however, this portion is optional and if patient is otherwise eligible, can enroll in&#xD;
             study without participating in imaging study)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maryam Lustberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ohio State University Comprehensive Cancer Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://cancer.osu.edu</url>
    <description>The Jamesline</description>
  </link>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>July 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 30, 2014</study_first_posted>
  <last_update_submitted>January 14, 2021</last_update_submitted>
  <last_update_submitted_qc>January 14, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ohio State University Comprehensive Cancer Center</investigator_affiliation>
    <investigator_full_name>Maryam Lustberg</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Breast Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Anxiety Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Minocycline</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>October 6, 2022</submitted>
    <returned>November 3, 2022</returned>
    <submitted>August 1, 2023</submitted>
    <returned>August 23, 2023</returned>
  </pending_results>
  <!-- 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/NCT02203552
org study id: OSU-13165
secondary id: NCI-2014-00851
nct id: NCT02203552
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This randomized clinical trial studies how well minocycline hydrochloride works in reducing
      chemotherapy induced depression and anxiety in patients with stage I-III breast cancer.
      Minocycline hydrochloride may prevent changes in memory and thinking and improve the quality
      of life of breast cancer patients receiving chemotherapy.
PRIMARY OBJECTIVES:

      I. To evaluate anxiety and depression in women with stages I-III breast cancer during the
      first 8 weeks of doxorubicin-based adjuvant therapy randomized to receive either minocycline
      (minocycline hydrochloride) or placebo.

      II. To evaluate markers of neuro-inflammation as assessed by blood based inflammatory
      cytokines and C11-choline positron emission tomography (PET) in women with stages I-III
      breast cancer during the first 8 weeks of doxorubicin-based adjuvant therapy randomized to
      receive either minocycline or placebo.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Beginning 1 week prior to chemotherapy, patients receive minocycline hydrochloride
      orally (PO) twice daily (BID) for 9 weeks.

      ARM II: Beginning 1 week prior to chemotherapy, patients receive placebo PO BID for 9 weeks.

      After completion of study treatment, patients are followed up for 6 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Changes in Center for Epidemiological Studies Depression Scale (CES-D) scores
time frame: Baseline to 9 weeks
description: The 95% confidence intervals of the depression change from baseline to the end of study and the difference between the treatment and placebo groups. The influences of covariate, such as disease stage and depression drug usage, will be considered in the mixed models as exploratory analyses.
measure: Changes in the State Trait Anxiety Index (STAI) scores
time frame: Baseline to 9 weeks
description: The 95% confidence intervals of the anxiety change from baseline to the end of study and the difference between the treatment and placebo groups. The influences of covariate, such as disease stage and depression drug usage, will be considered in the mixed models as exploratory analyses.
measure: Changes in Hamilton Anxiety Rating Scale scores
time frame: Baseline to 9 weeks
description: The 95% confidence intervals of the anxiety change from baseline to the end of study and the difference between the treatment and placebo groups. The influences of covariate, such as disease stage and depression drug usage, will be considered in the mixed models as exploratory analyses. In addition, change overtime of all outcomes for each individual will be plotted to visually explore any patterns and to generate hypothesis to be tested in future studies.
measure: Changes in Hamilton Rating Scale for Depression scores
time frame: Baseline to 9 weeks
description: The 95% confidence intervals of the depression change from baseline to the end of study and the difference between the treatment and placebo groups. The influences of covariate, such as disease stage and depression drug usage, will be considered in the mixed models as exploratory analyses. In addition, change overtime of all outcomes for each individual will be plotted to visually explore any patterns and to generate hypothesis to be tested in future studies.
measure: Changes in inflammatory blood markers
time frame: Baseline to 6 months
description: Scatter plots will be used to explore the pair-wise correlation among the changes of CES-D and STAI scores, blood biomarkers changes, and PET/MRI measures. A statistical model will be used to explore whether the blood based biomarkers and PET/MRI measures can be used to predict the changes in CES-D and STAI scores, which then could be used as potential surrogate markers in future studies.
measure: Changes in the PET/MRI measures
time frame: Baseline to 6 months
description: Scatter plots will be used to explore the pair-wise correlation among the changes of CES-D and STAI scores, blood biomarkers changes, and PET/MRI measures. A statistical model will be used to explore whether the blood based biomarkers and PET/MRI measures can be used to predict the changes in CES-D and STAI scores, which then could be used as potential surrogate markers in future studies.
arm group label: Arm I (minocycline hydrochloride)
arm group type: Experimental
description: Beginning 1 week prior to chemotherapy, patients receive minocycline hydrochloride orally PO BID for 9 weeks. Laboratory biomarker analysis will also be obtained weekly on protocol. Questionnaire administration weekly.
arm group label: Arm II (placebo)
arm group type: Placebo Comparator
description: Beginning 1 week prior to chemotherapy, patients receive placebo PO BID for 9 weeks. Laboratory biomarker analysis will also be obtained weekly on protocol. Questionnaire administration weekly.
intervention type: Drug
intervention name: minocycline hydrochloride
description: 100 mg bid given by mouth for 9 weeks
arm group label: Arm I (minocycline hydrochloride)
other name: Dynacin
other name: Minocin
other name: Minomax
other name: Minomycin
intervention type: Other
intervention name: placebo
description: Placebo given by mouth for 9 weeks
arm group label: Arm II (placebo)
other name: PLCB
intervention type: Other
intervention name: laboratory biomarker analysis
description: Correlative blood levels for cortisol, high sensitivity c-reactive protein (hs-CRP) and inflammatory factors including but not limited to IL-6, TNF-α, IL-1β, and MCP-1 will also be obtained weekly on protocol.
arm group label: Arm I (minocycline hydrochloride)
arm group label: Arm II (placebo)
other name: special studies
other name: Correlative studies
intervention type: Other
intervention name: Questionnaire administration
description: The CES-D and STAI will be administrated weekly.
arm group label: Arm I (minocycline hydrochloride)
arm group label: Arm II (placebo)
other name: Ancillary studies
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Maryam Lustberg, MD
role: Principal Investigator
affiliation: Ohio State University Comprehensive Cancer Center
facility: 
country: United States
url: http://cancer.osu.edu
description: The Jamesline
responsible party type: Principal Investigator
investigator affiliation: Ohio State University Comprehensive Cancer Center
investigator full name: Maryam Lustberg
investigator title: Principal Investigator
mesh term: Breast Neoplasms
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Anxiety Disorders
mesh term: Minocycline
sharing ipd: No
submitted: October 6, 2022
returned: November 3, 2022
submitted: August 1, 2023
returned: August 23, 2023