<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/NCT03253627</url>
  </required_header>
  <id_info>
    <org_study_id>s17-00995</org_study_id>
    <secondary_id>4R00NR015473-03</secondary_id>
    <nct_id>NCT03253627</nct_id>
  </id_info>
  <brief_title>MBSR During AI Therapy for Breast Cancer</brief_title>
  <official_title>Mindfulness-Based Stress Reduction To Improve Cognitive Function for Postmenopausal Women With Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>New York University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Nursing Research (NINR)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>New York University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will use non-invasive neuroimaging (i.e., MRI) to examine whether&#xD;
      Mindfulness-Based Stress Reduction (MBSR) improves neural markers of cognitive function for&#xD;
      postmenopausal women taking aromatase inhibitor (AI) therapy for breast cancer. The pilot&#xD;
      randomized controlled trial will obtain preliminary efficacy of MBSR versus Health&#xD;
      Enhancement Program (HEP) active control to improve neural markers of cognitive function. The&#xD;
      final sample will include 32 postmenopausal women with breast cancer. MBSR and HEP groups&#xD;
      will meet for a matched schedule of 8 weekly 2.5-hour sessions and a one-day weekend retreat.&#xD;
      Specimen and data collection will be done at three time points: pre-randomization (i.e.,&#xD;
      within three weeks before beginning the intervention), within three weeks after completion of&#xD;
      the intervention, and approximately three months (+/- three weeks) post intervention. Change&#xD;
      scores for neuroimaging parameter estimates will be correlated with change scores for&#xD;
      measures of cognitive function and affect. Differential expression of genes will be&#xD;
      correlated with neuroimaging parameter estimates.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Adjuvant aromatase inhibitor (AI) therapy improves disease-free and overall survival for&#xD;
      postmenopausal women after surgery for hormone receptor-positive breast cancer. Among&#xD;
      symptoms associated with AI therapy are changes in cognitive function. Up to 25% of&#xD;
      postmenopausal women with breast cancer report that they experience changes in cognitive&#xD;
      function during AI therapy. Studies using neuropsychological tests found subtle&#xD;
      deteriorations in verbal and visual learning and memory-as well as concentration, working&#xD;
      memory, and executive function-for as many as a third of these patients. Changes in cognitive&#xD;
      function may be associated with changes in affect (e.g., worry, depressive symptoms). Neural&#xD;
      markers of cognitive changes, including changes in brain function and structure, may underlie&#xD;
      changes in cognitive function.&#xD;
&#xD;
      The investigators' recent preliminary neuroimaging work to describe neural markers of&#xD;
      cognitive changes suggests that postmenopausal women with breast cancer have inefficient&#xD;
      cognitive-emotion processing before AI therapy, as evidenced by greater neural activity in&#xD;
      the hippocampus (working memory) and amygdala (emotion processing) during task performance&#xD;
      compared to controls. During AI therapy, patients show differential activation compared to&#xD;
      controls in the dorsolateral prefrontal cortex (executive function and working memory),&#xD;
      medial prefrontal cortices (cortical control of amygdala responses), and hippocampus.&#xD;
&#xD;
      Stress responses could partially explain relationships between AI therapy and neural markers&#xD;
      of cognitive changes. The Mindfulness Stress-Buffering Account suggests that interventions&#xD;
      such as Mindfulness-Based Stress Reduction (MBSR) may improve stress responses by attenuating&#xD;
      negative appraisals of stress and reducing reactivity to stressful situations. For example,&#xD;
      mindfulness meditation improved psychological stress responses in women with breast cancer.&#xD;
      It improved some measures of cognitive function. Mindfulness practices reduced physiological&#xD;
      markers of stress responses, including inflammatory markers in women with breast cancer and&#xD;
      in stressed community adults, as well as cortisol reactivity for breast cancer survivors and&#xD;
      during chemotherapy for colorectal cancer. Although similar neural deficits as were found in&#xD;
      the investigators' preliminary work have been shown to improve in stressed adult populations&#xD;
      using MBSR, it is not known whether the intervention improves neural deficits in women taking&#xD;
      AI therapy (estrogen, production of which is blocked by AI therapy, is neuroprotective and&#xD;
      promotes neural plasticity). Genetic variability was previously found to moderate the effect&#xD;
      of MBSR on self-reported cognitive function. Therefore, it is possible that inter-individual&#xD;
      variability in the expression of genes involved in stress responses could moderate&#xD;
      relationships between AI therapy and neural markers of cognitive changes during MBSR. Taken&#xD;
      together, MBSR may improve neural markers of cognitive changes shown in preliminary work to&#xD;
      be deficient in postmenopausal women before and during AI therapy for breast cancer by&#xD;
      targeting stress responses. Changes in these neural markers may correspond to improved&#xD;
      self-report and neuropsychological measures of cognitive function.&#xD;
&#xD;
      Hypothesis: Stress reduction, moderated by gene expression, blunts the impact of AI therapy&#xD;
      on neural markers of cognitive function, thereby improving cognitive function and affect in&#xD;
      women with breast cancer.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 23, 2018</start_date>
  <completion_date type="Actual">September 8, 2020</completion_date>
  <primary_completion_date type="Actual">December 10, 2019</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>A pilot, single-center randomized controlled trial of the preliminary efficacy of an eight-week, group-based Mindfulness-Based Stress Reduction intervention versus Health Enhancement Program active control (i.e., two groups, parallel design) to improve neural markers of changes in cognitive function in postmenopausal women receiving aromatase inhibitor therapy for breast cancer. Participants will be stratified in a permuted block design by receipt of chemotherapy (i.e., two strata). Data will be collected at up to three time points using a repeated measures design (i.e., pre-intervention, post-intervention, approximately three months after the intervention). The study groups will meet at NYU for MBSR or HEP. Neuropsychological, self-report, and biospecimen data collection will be conducted at the Bluestone Center. Neuroimaging data will be collected at the NYU Center for Brain Imaging.</intervention_model_description>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
    <masking_description>Participants will complete the baseline assessment and be randomly assigned to study group in a permuted block design stratified by receipt of chemotherapy (i.e., two strata). It will not be possible to blind study participants or interventionists to group assignment. To reduce bias, research staff who conduct assessments, including the PI, will be blinded to group assignment (i.e., single blind). Participants will be reminded not to reveal their group assignment to study staff conducting assessments. The study biostatistician will have no direct contact with study participants and will not be blinded to group assignment. The biostatistician will produce and maintain the randomization codes for the permuted blocks. Randomization may only be unmasked by the biostatistician at the completion of data collection, or for reporting of serious adverse events or unanticipated problems for which it will be essential to provide information to the PI on group assignment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Functional Neural Activation Parameter Estimate</measure>
    <time_frame>baseline, 3 months</time_frame>
    <description>global maximum cluster-level neural activation during task-based functional magnetic resonance imaging for MBSR group compared to Health Enhancement Program group in a whole-brain analysis; paradigm: Emotional Faces N-Back; conditions: happy face distractors minus no face distractors; value has no minimum or maximum; value has no reference ranges; higher values indicate more neural activation</description>
  </primary_outcome>
  <other_outcome>
    <measure>List Sorting Working Memory Test</measure>
    <time_frame>baseline, 6 months</time_frame>
    <description>from National Institutes of Health (NIH) Toolbox; Age 7+ v2.1; measures working memory; T-score range 23-77; 50 indicates the population mean with a standard deviation of 10; higher scores indicate better working memory performance; scores below 40 suggest cognitive impairment</description>
  </other_outcome>
  <other_outcome>
    <measure>Flanker Inhibitory Control and Attention Test</measure>
    <time_frame>baseline, 6 months</time_frame>
    <description>from National Institutes of Health (NIH) Toolbox; Age 12+ v2.1; measures attention; T-score range 23-77; 50 indicates the population mean with a standard deviation of 10; higher scores indicate better attention performance; scores below 40 suggest cognitive impairment</description>
  </other_outcome>
  <other_outcome>
    <measure>Cognitive Function</measure>
    <time_frame>baseline, 3 months, 6 months</time_frame>
    <description>From the Quality of Life in Neurological Disorders (Neuro-QoL) Bank; v2.0; patient-reported outcome; measures executive function and general cognitive concerns; T-score range 17.3-64.2; 50 indicates the population mean with a standard deviation of 10; higher scores indicate better self-reported cognitive function; scores 41-45 suggest mild cognitive impairment, 31-40 suggest moderate cognitive impairment, and 30 or below suggest severe cognitive impairment</description>
  </other_outcome>
  <other_outcome>
    <measure>Anxiety</measure>
    <time_frame>baseline, 3 months, 6 months</time_frame>
    <description>From the Quality of Life in Neurological Disorders (Neuro-QoL) Bank; v1.0; patient reported outcome; T-score range 36.4-76.8; 50 indicates the population mean with a standard deviation of 10; higher scores indicate worse self-reported anxiety; scores 55-59 suggest mild anxiety, 60-69 suggest moderate anxiety, and 70 or above suggest severe anxiety</description>
  </other_outcome>
  <other_outcome>
    <measure>Depression</measure>
    <time_frame>baseline, 3 months, 6 months</time_frame>
    <description>From the Quality of Life in Neurological Disorders (Neuro-QoL) Bank; v1.0; patient-reported outcome; measures depressive symptoms; T-score range 36.9-75.0; 50 indicates the population mean with a standard deviation of 10; higher scores indicate worse depressive symptoms; scores 55-59 suggest mild depressive symptoms, 60-69 suggest moderate depressive symptoms, and 70 or above suggest severe depressive symptoms</description>
  </other_outcome>
  <other_outcome>
    <measure>Gene Expression</measure>
    <time_frame>baseline, 3 months, 6 months</time_frame>
    <description>AMIGO1 gene expression in raw gene counts for MBSR group compared to Health Enhancement Program group in a whole transcriptome analysis using ribonucleic acid sequencing (RNA-Seq); minimum 0, no maximum; value has no reference ranges; higher values indicate more gene expression</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Breast Cancer</condition>
  <condition>Cognitive Symptom</condition>
  <arm_group>
    <arm_group_label>MBSR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mindfulness-Based Stress Reduction</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Health Enhancement Program</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Health Enhancement Program</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Health Enhancement Program</intervention_name>
    <description>The HEP control, which was developed to serve as an active control to MBSR, will receive manualized health education from experts in physical activity, functional movement, music therapy, and nutrition-without mindfulness instruction-using similar modalities to MBSR training for a matched schedule.</description>
    <arm_group_label>Health Enhancement Program</arm_group_label>
    <other_name>HEP</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Mindfulness-Based Stress Reduction</intervention_name>
    <description>The MBSR group will receive training from a certified instructor during a group-based, 2.5-hour manualized educational activity weekly for eight weeks. Activities include body scans, gentle stretching, yoga, and mindful awareness. Participants will be asked to complete daily 45-minute, audio-guided mindfulness activities and a one-day weekend retreat to reinforce learning.</description>
    <arm_group_label>MBSR</arm_group_label>
    <other_name>MBSR</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Female&#xD;
&#xD;
          2. &lt;80 years of age by date of baseline assessment visit&#xD;
&#xD;
          3. Able to speak and read English&#xD;
&#xD;
          4. Post-menopausal (defined as [A] amenorrhea persisting for an entire year, [B]&#xD;
             oophorectomy or ovarian suppression/ablation, or [C] hysterectomy and age &gt;51 years)&#xD;
&#xD;
          5. Diagnosed with DCIS (stage 0) or stage I, II, or III breast cancer&#xD;
&#xD;
          6. Post lumpectomy or mastectomy and any re-excisions&#xD;
&#xD;
          7. Post neoadjuvant or adjuvant chemotherapy, if prescribed&#xD;
&#xD;
          8. Taking aromatase inhibitor (AI) therapy OR AI therapy scheduled to begin before&#xD;
             planned post-intervention assessment visit&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Stage IV (metastatic) breast cancer&#xD;
&#xD;
          2. Diagnosis of a major psychiatric disorder (e.g., bipolar I disorder, schizophrenia,&#xD;
             schizoaffective disorder)&#xD;
&#xD;
          3. Suicide attempt within the last 10 years&#xD;
&#xD;
          4. Hospitalization or residential treatment for psychiatric illness, eating disorder, or&#xD;
             substance abuse within the last 2 years&#xD;
&#xD;
          5. History of neurological disease (e.g., Parkinson's disease, dementia)&#xD;
&#xD;
          6. History of head trauma&#xD;
&#xD;
          7. Claustrophobia&#xD;
&#xD;
          8. Unable to lie on the back&#xD;
&#xD;
          9. Ever been told not to get an MRI&#xD;
&#xD;
         10. MRI-incompatible metal implant*&#xD;
&#xD;
               -  If a potential participant reports implanted metal objects, which might be&#xD;
                  affected by MRI magnets, the study personnel and MRI technologist will screen&#xD;
                  over the phone or in person to determine whether the potential participant would&#xD;
                  be safe during the MRI scan. A current list of implants compatible with MRI will&#xD;
                  be consulted (http://www.mrisafety.com/TMDL_list.php).&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John D Merriman, PhD, RN</last_name>
    <role>Principal Investigator</role>
    <affiliation>New York University Meyers College of Nursing</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>New York University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>August 8, 2017</study_first_submitted>
  <study_first_submitted_qc>August 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <results_first_submitted>November 29, 2021</results_first_submitted>
  <results_first_submitted_qc>April 27, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">May 19, 2022</results_first_posted>
  <last_update_submitted>October 31, 2022</last_update_submitted>
  <last_update_submitted_qc>October 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Neurobehavioral Manifestations</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Even though the R00 study is not anticipated to reach the threshold for required genomic data sharing, the study will have in place plans for sharing de-identified data for secondary analyses with qualified investigators. The consent language for the R00 study will be worded for possible broad data sharing.</ipd_description>
    <ipd_time_frame>The timeline for submission to an NIH-designated data repository will allow first for publication of findings related to the aims of the R00 study, as well as submission of findings as preliminary data for anticipated grant application(s).</ipd_time_frame>
    <ipd_access_criteria>The investigators plan to submit genomic data and relevant phenotypic data (e.g., clinical characteristics of the sample) generated in the R00 study to an NIH-designated data repository in a timely manner. The submission process will likely include registration in the database of Genotypes and Phenotypes (dbGaP) and submission to Gene Expression Omnibus (GEO) for controlled access to the data.</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 16, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/27/NCT03253627/Prot_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 8, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/27/NCT03253627/SAP_002.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>August 23, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/27/NCT03253627/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>NYU was activated as a site in September 2017. Recruitment and screening began in January 2018. Enrollment started in April 2018 and ended in October 2019. Bellevue Hospital site approval was received in July 2019. Enrollment began then in its affiliated clinics and ended in October 2019.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>MBSR</title>
          <description>Mindfulness-Based Stress Reduction&#xD;
Mindfulness-Based Stress Reduction: The MBSR group will receive training from a certified instructor during a group-based, 2.5-hour manualized educational activity weekly for eight weeks. Activities include body scans, gentle stretching, yoga, and mindful awareness. Participants will be asked to complete daily 45-minute, audio-guided mindfulness activities and a one-day weekend retreat to reinforce learning.</description>
        </group>
        <group group_id="P2">
          <title>Health Enhancement Program</title>
          <description>Health Enhancement Program&#xD;
Health Enhancement Program: The HEP control, which was developed to serve as an active control to MBSR, will receive manualized health education from experts in physical activity, functional movement, music therapy, and nutrition-without mindfulness instruction-using similar modalities to MBSR training for a matched schedule.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Post-intervention</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Inability to complete MRI</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>MBSR</title>
          <description>Mindfulness-Based Stress Reduction&#xD;
Mindfulness-Based Stress Reduction: The MBSR group will receive training from a certified instructor during a group-based, 2.5-hour manualized educational activity weekly for eight weeks. Activities include body scans, gentle stretching, yoga, and mindful awareness. Participants will be asked to complete daily 45-minute, audio-guided mindfulness activities and a one-day weekend retreat to reinforce learning.</description>
        </group>
        <group group_id="B2">
          <title>Health Enhancement Program</title>
          <description>Health Enhancement Program&#xD;
Health Enhancement Program: The HEP control, which was developed to serve as an active control to MBSR, will receive manualized health education from experts in physical activity, functional movement, music therapy, and nutrition-without mindfulness instruction-using similar modalities to MBSR training for a matched schedule.</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="12"/>
            <count group_id="B2" value="11"/>
            <count group_id="B3" value="23"/>
          </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="65.9" spread="4.85"/>
                    <measurement group_id="B2" value="55.6" spread="10.51"/>
                    <measurement group_id="B3" value="61" spread="9.46"/>
                  </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="12"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</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>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="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="22"/>
                  </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>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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>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="12"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Functional Neural Activation Parameter Estimate</title>
        <description>global maximum cluster-level neural activation during task-based functional magnetic resonance imaging for MBSR group compared to Health Enhancement Program group in a whole-brain analysis; paradigm: Emotional Faces N-Back; conditions: happy face distractors minus no face distractors; value has no minimum or maximum; value has no reference ranges; higher values indicate more neural activation</description>
        <time_frame>baseline, 3 months</time_frame>
        <population>participants with usable neuroimaging data after quality control</population>
        <group_list>
          <group group_id="O1">
            <title>MBSR</title>
            <description>Mindfulness-Based Stress Reduction&#xD;
Mindfulness-Based Stress Reduction: The MBSR group will receive training from a certified instructor during a group-based, 2.5-hour manualized educational activity weekly for eight weeks. Activities include body scans, gentle stretching, yoga, and mindful awareness. Participants will be asked to complete daily 45-minute, audio-guided mindfulness activities and a one-day weekend retreat to reinforce learning.</description>
          </group>
          <group group_id="O2">
            <title>Health Enhancement Program</title>
            <description>Health Enhancement Program&#xD;
Health Enhancement Program: The HEP control, which was developed to serve as an active control to MBSR, will receive manualized health education from experts in physical activity, functional movement, music therapy, and nutrition-without mindfulness instruction-using similar modalities to MBSR training for a matched schedule.</description>
          </group>
        </group_list>
        <measure>
          <title>Functional Neural Activation Parameter Estimate</title>
          <description>global maximum cluster-level neural activation during task-based functional magnetic resonance imaging for MBSR group compared to Health Enhancement Program group in a whole-brain analysis; paradigm: Emotional Faces N-Back; conditions: happy face distractors minus no face distractors; value has no minimum or maximum; value has no reference ranges; higher values indicate more neural activation</description>
          <population>participants with usable neuroimaging data after quality control</population>
          <units>beta weights</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.2" spread="2.27"/>
                    <measurement group_id="O2" value="-1.8" spread="2.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" spread="1.95"/>
                    <measurement group_id="O2" value="-0.7" spread="2.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>baseline</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.460</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>3 months</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.896</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>List Sorting Working Memory Test</title>
        <description>from National Institutes of Health (NIH) Toolbox; Age 7+ v2.1; measures working memory; T-score range 23-77; 50 indicates the population mean with a standard deviation of 10; higher scores indicate better working memory performance; scores below 40 suggest cognitive impairment</description>
        <time_frame>baseline, 6 months</time_frame>
        <population>differences in sample size due to attrition</population>
        <group_list>
          <group group_id="O1">
            <title>MBSR</title>
            <description>Mindfulness-Based Stress Reduction&#xD;
Mindfulness-Based Stress Reduction: The MBSR group will receive training from a certified instructor during a group-based, 2.5-hour manualized educational activity weekly for eight weeks. Activities include body scans, gentle stretching, yoga, and mindful awareness. Participants will be asked to complete daily 45-minute, audio-guided mindfulness activities and a one-day weekend retreat to reinforce learning.</description>
          </group>
          <group group_id="O2">
            <title>Health Enhancement Program</title>
            <description>Health Enhancement Program&#xD;
Health Enhancement Program: The HEP control, which was developed to serve as an active control to MBSR, will receive manualized health education from experts in physical activity, functional movement, music therapy, and nutrition-without mindfulness instruction-using similar modalities to MBSR training for a matched schedule.</description>
          </group>
        </group_list>
        <measure>
          <title>List Sorting Working Memory Test</title>
          <description>from National Institutes of Health (NIH) Toolbox; Age 7+ v2.1; measures working memory; T-score range 23-77; 50 indicates the population mean with a standard deviation of 10; higher scores indicate better working memory performance; scores below 40 suggest cognitive impairment</description>
          <population>differences in sample size due to attrition</population>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="11"/>
              </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="12"/>
                    <count group_id="O2" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.7" spread="6.05"/>
                    <measurement group_id="O2" value="51.5" spread="8.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.5" spread="8.57"/>
                    <measurement group_id="O2" value="56.3" spread="10.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>baseline</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.374</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 months</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.236</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Flanker Inhibitory Control and Attention Test</title>
        <description>from National Institutes of Health (NIH) Toolbox; Age 12+ v2.1; measures attention; T-score range 23-77; 50 indicates the population mean with a standard deviation of 10; higher scores indicate better attention performance; scores below 40 suggest cognitive impairment</description>
        <time_frame>baseline, 6 months</time_frame>
        <population>Differences in sample size due to attrition</population>
        <group_list>
          <group group_id="O1">
            <title>MBSR</title>
            <description>Mindfulness-Based Stress Reduction&#xD;
Mindfulness-Based Stress Reduction: The MBSR group will receive training from a certified instructor during a group-based, 2.5-hour manualized educational activity weekly for eight weeks. Activities include body scans, gentle stretching, yoga, and mindful awareness. Participants will be asked to complete daily 45-minute, audio-guided mindfulness activities and a one-day weekend retreat to reinforce learning.</description>
          </group>
          <group group_id="O2">
            <title>Health Enhancement Program</title>
            <description>Health Enhancement Program&#xD;
Health Enhancement Program: The HEP control, which was developed to serve as an active control to MBSR, will receive manualized health education from experts in physical activity, functional movement, music therapy, and nutrition-without mindfulness instruction-using similar modalities to MBSR training for a matched schedule.</description>
          </group>
        </group_list>
        <measure>
          <title>Flanker Inhibitory Control and Attention Test</title>
          <description>from National Institutes of Health (NIH) Toolbox; Age 12+ v2.1; measures attention; T-score range 23-77; 50 indicates the population mean with a standard deviation of 10; higher scores indicate better attention performance; scores below 40 suggest cognitive impairment</description>
          <population>Differences in sample size due to attrition</population>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="11"/>
              </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="12"/>
                    <count group_id="O2" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.5" spread="8.17"/>
                    <measurement group_id="O2" value="41.9" spread="7.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.3" spread="3.83"/>
                    <measurement group_id="O2" value="42.4" spread="11.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>baseline</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.180</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 months</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.822</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Cognitive Function</title>
        <description>From the Quality of Life in Neurological Disorders (Neuro-QoL) Bank; v2.0; patient-reported outcome; measures executive function and general cognitive concerns; T-score range 17.3-64.2; 50 indicates the population mean with a standard deviation of 10; higher scores indicate better self-reported cognitive function; scores 41-45 suggest mild cognitive impairment, 31-40 suggest moderate cognitive impairment, and 30 or below suggest severe cognitive impairment</description>
        <time_frame>baseline, 3 months, 6 months</time_frame>
        <population>Differences in sample size due to attrition</population>
        <group_list>
          <group group_id="O1">
            <title>MBSR</title>
            <description>Mindfulness-Based Stress Reduction&#xD;
Mindfulness-Based Stress Reduction: The MBSR group will receive training from a certified instructor during a group-based, 2.5-hour manualized educational activity weekly for eight weeks. Activities include body scans, gentle stretching, yoga, and mindful awareness. Participants will be asked to complete daily 45-minute, audio-guided mindfulness activities and a one-day weekend retreat to reinforce learning.</description>
          </group>
          <group group_id="O2">
            <title>Health Enhancement Program</title>
            <description>Health Enhancement Program&#xD;
Health Enhancement Program: The HEP control, which was developed to serve as an active control to MBSR, will receive manualized health education from experts in physical activity, functional movement, music therapy, and nutrition-without mindfulness instruction-using similar modalities to MBSR training for a matched schedule.</description>
          </group>
        </group_list>
        <measure>
          <title>Cognitive Function</title>
          <description>From the Quality of Life in Neurological Disorders (Neuro-QoL) Bank; v2.0; patient-reported outcome; measures executive function and general cognitive concerns; T-score range 17.3-64.2; 50 indicates the population mean with a standard deviation of 10; higher scores indicate better self-reported cognitive function; scores 41-45 suggest mild cognitive impairment, 31-40 suggest moderate cognitive impairment, and 30 or below suggest severe cognitive impairment</description>
          <population>Differences in sample size due to attrition</population>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="11"/>
              </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="12"/>
                    <count group_id="O2" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.0" spread="6.49"/>
                    <measurement group_id="O2" value="45.9" spread="8.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.4" spread="5.12"/>
                    <measurement group_id="O2" value="46.0" spread="8.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.4" spread="6.37"/>
                    <measurement group_id="O2" value="46.4" spread="7.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>baseline</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.715</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>3 months</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.861</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 months</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.790</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Anxiety</title>
        <description>From the Quality of Life in Neurological Disorders (Neuro-QoL) Bank; v1.0; patient reported outcome; T-score range 36.4-76.8; 50 indicates the population mean with a standard deviation of 10; higher scores indicate worse self-reported anxiety; scores 55-59 suggest mild anxiety, 60-69 suggest moderate anxiety, and 70 or above suggest severe anxiety</description>
        <time_frame>baseline, 3 months, 6 months</time_frame>
        <population>Differences in sample size due to attrition</population>
        <group_list>
          <group group_id="O1">
            <title>MBSR</title>
            <description>Mindfulness-Based Stress Reduction&#xD;
Mindfulness-Based Stress Reduction: The MBSR group will receive training from a certified instructor during a group-based, 2.5-hour manualized educational activity weekly for eight weeks. Activities include body scans, gentle stretching, yoga, and mindful awareness. Participants will be asked to complete daily 45-minute, audio-guided mindfulness activities and a one-day weekend retreat to reinforce learning.</description>
          </group>
          <group group_id="O2">
            <title>Health Enhancement Program</title>
            <description>Health Enhancement Program&#xD;
Health Enhancement Program: The HEP control, which was developed to serve as an active control to MBSR, will receive manualized health education from experts in physical activity, functional movement, music therapy, and nutrition-without mindfulness instruction-using similar modalities to MBSR training for a matched schedule.</description>
          </group>
        </group_list>
        <measure>
          <title>Anxiety</title>
          <description>From the Quality of Life in Neurological Disorders (Neuro-QoL) Bank; v1.0; patient reported outcome; T-score range 36.4-76.8; 50 indicates the population mean with a standard deviation of 10; higher scores indicate worse self-reported anxiety; scores 55-59 suggest mild anxiety, 60-69 suggest moderate anxiety, and 70 or above suggest severe anxiety</description>
          <population>Differences in sample size due to attrition</population>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="11"/>
              </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="12"/>
                    <count group_id="O2" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.3" spread="5.40"/>
                    <measurement group_id="O2" value="53.1" spread="5.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.8" spread="6.91"/>
                    <measurement group_id="O2" value="53.9" spread="12.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.7" spread="7.56"/>
                    <measurement group_id="O2" value="50.3" spread="12.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>baseline</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.452</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>3 months</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.253</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 months</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.469</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Depression</title>
        <description>From the Quality of Life in Neurological Disorders (Neuro-QoL) Bank; v1.0; patient-reported outcome; measures depressive symptoms; T-score range 36.9-75.0; 50 indicates the population mean with a standard deviation of 10; higher scores indicate worse depressive symptoms; scores 55-59 suggest mild depressive symptoms, 60-69 suggest moderate depressive symptoms, and 70 or above suggest severe depressive symptoms</description>
        <time_frame>baseline, 3 months, 6 months</time_frame>
        <population>Differences in sample size due to attrition</population>
        <group_list>
          <group group_id="O1">
            <title>MBSR</title>
            <description>Mindfulness-Based Stress Reduction&#xD;
Mindfulness-Based Stress Reduction: The MBSR group will receive training from a certified instructor during a group-based, 2.5-hour manualized educational activity weekly for eight weeks. Activities include body scans, gentle stretching, yoga, and mindful awareness. Participants will be asked to complete daily 45-minute, audio-guided mindfulness activities and a one-day weekend retreat to reinforce learning.</description>
          </group>
          <group group_id="O2">
            <title>Health Enhancement Program</title>
            <description>Health Enhancement Program&#xD;
Health Enhancement Program: The HEP control, which was developed to serve as an active control to MBSR, will receive manualized health education from experts in physical activity, functional movement, music therapy, and nutrition-without mindfulness instruction-using similar modalities to MBSR training for a matched schedule.</description>
          </group>
        </group_list>
        <measure>
          <title>Depression</title>
          <description>From the Quality of Life in Neurological Disorders (Neuro-QoL) Bank; v1.0; patient-reported outcome; measures depressive symptoms; T-score range 36.9-75.0; 50 indicates the population mean with a standard deviation of 10; higher scores indicate worse depressive symptoms; scores 55-59 suggest mild depressive symptoms, 60-69 suggest moderate depressive symptoms, and 70 or above suggest severe depressive symptoms</description>
          <population>Differences in sample size due to attrition</population>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="11"/>
              </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="12"/>
                    <count group_id="O2" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.3" spread="6.31"/>
                    <measurement group_id="O2" value="45.3" spread="3.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.0" spread="6.78"/>
                    <measurement group_id="O2" value="49.7" spread="10.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.9" spread="7.24"/>
                    <measurement group_id="O2" value="48.4" spread="8.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>baseline</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.628</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>3 months</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.345</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 months</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.384</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Gene Expression</title>
        <description>AMIGO1 gene expression in raw gene counts for MBSR group compared to Health Enhancement Program group in a whole transcriptome analysis using ribonucleic acid sequencing (RNA-Seq); minimum 0, no maximum; value has no reference ranges; higher values indicate more gene expression</description>
        <time_frame>baseline, 3 months, 6 months</time_frame>
        <population>participants with usable gene expression data after quality control</population>
        <group_list>
          <group group_id="O1">
            <title>MBSR</title>
            <description>Mindfulness-Based Stress Reduction&#xD;
Mindfulness-Based Stress Reduction: The MBSR group will receive training from a certified instructor during a group-based, 2.5-hour manualized educational activity weekly for eight weeks. Activities include body scans, gentle stretching, yoga, and mindful awareness. Participants will be asked to complete daily 45-minute, audio-guided mindfulness activities and a one-day weekend retreat to reinforce learning.</description>
          </group>
          <group group_id="O2">
            <title>Health Enhancement Program</title>
            <description>Health Enhancement Program&#xD;
Health Enhancement Program: The HEP control, which was developed to serve as an active control to MBSR, will receive manualized health education from experts in physical activity, functional movement, music therapy, and nutrition-without mindfulness instruction-using similar modalities to MBSR training for a matched schedule.</description>
          </group>
        </group_list>
        <measure>
          <title>Gene Expression</title>
          <description>AMIGO1 gene expression in raw gene counts for MBSR group compared to Health Enhancement Program group in a whole transcriptome analysis using ribonucleic acid sequencing (RNA-Seq); minimum 0, no maximum; value has no reference ranges; higher values indicate more gene expression</description>
          <population>participants with usable gene expression data after quality control</population>
          <units>raw gene counts</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
              </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="9"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="106.1" spread="74.98"/>
                    <measurement group_id="O2" value="137.3" spread="77.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>3 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="196.0" spread="210.74"/>
                    <measurement group_id="O2" value="176.3" spread="114.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 months</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="114.4" spread="81.11"/>
                    <measurement group_id="O2" value="218.3" spread="86.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>baseline</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.398</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>3 months</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.811</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>6 months</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.027</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>For each participant, adverse event data were collected from the date of enrollment through the final assessment (i.e., approximately 6 months after enrollment).</time_frame>
      <desc>questionnaire at each follow-up assessment (i.e., post intervention, 3 months post intervention)</desc>
      <group_list>
        <group group_id="E1">
          <title>MBSR</title>
          <description>Mindfulness-Based Stress Reduction&#xD;
Mindfulness-Based Stress Reduction: The MBSR group will receive training from a certified instructor during a group-based, 2.5-hour manualized educational activity weekly for eight weeks. Activities include body scans, gentle stretching, yoga, and mindful awareness. Participants will be asked to complete daily 45-minute, audio-guided mindfulness activities and a one-day weekend retreat to reinforce learning.</description>
        </group>
        <group group_id="E2">
          <title>Health Enhancement Program</title>
          <description>Health Enhancement Program&#xD;
Health Enhancement Program: The HEP control, which was developed to serve as an active control to MBSR, will receive manualized health education from experts in physical activity, functional movement, music therapy, and nutrition-without mindfulness instruction-using similar modalities to MBSR training for a matched schedule.</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="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The sample was less than the anticipated final sample size of 32; it included fewer minority participants than planned. The advent of the COVID-19 pandemic prohibited further recruitment and conduct of this study, which had unavoidable in-person activities (e.g., neuroimaging).</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>John Merriman, PhD, RN</name_or_title>
      <organization>New York University Meyers College of Nursing</organization>
      <phone>212-998-5375</phone>
      <email>john.merriman@nyu.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/NCT03253627
org study id: s17-00995
secondary id: 4R00NR015473-03
nct id: NCT03253627
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will use non-invasive neuroimaging (i.e., MRI) to examine whether
      Mindfulness-Based Stress Reduction (MBSR) improves neural markers of cognitive function for
      postmenopausal women taking aromatase inhibitor (AI) therapy for breast cancer. The pilot
      randomized controlled trial will obtain preliminary efficacy of MBSR versus Health
      Enhancement Program (HEP) active control to improve neural markers of cognitive function. The
      final sample will include 32 postmenopausal women with breast cancer. MBSR and HEP groups
      will meet for a matched schedule of 8 weekly 2.5-hour sessions and a one-day weekend retreat.
      Specimen and data collection will be done at three time points: pre-randomization (i.e.,
      within three weeks before beginning the intervention), within three weeks after completion of
      the intervention, and approximately three months (+/- three weeks) post intervention. Change
      scores for neuroimaging parameter estimates will be correlated with change scores for
      measures of cognitive function and affect. Differential expression of genes will be
      correlated with neuroimaging parameter estimates.
Adjuvant aromatase inhibitor (AI) therapy improves disease-free and overall survival for
      postmenopausal women after surgery for hormone receptor-positive breast cancer. Among
      symptoms associated with AI therapy are changes in cognitive function. Up to 25% of
      postmenopausal women with breast cancer report that they experience changes in cognitive
      function during AI therapy. Studies using neuropsychological tests found subtle
      deteriorations in verbal and visual learning and memory-as well as concentration, working
      memory, and executive function-for as many as a third of these patients. Changes in cognitive
      function may be associated with changes in affect (e.g., worry, depressive symptoms). Neural
      markers of cognitive changes, including changes in brain function and structure, may underlie
      changes in cognitive function.

      The investigators' recent preliminary neuroimaging work to describe neural markers of
      cognitive changes suggests that postmenopausal women with breast cancer have inefficient
      cognitive-emotion processing before AI therapy, as evidenced by greater neural activity in
      the hippocampus (working memory) and amygdala (emotion processing) during task performance
      compared to controls. During AI therapy, patients show differential activation compared to
      controls in the dorsolateral prefrontal cortex (executive function and working memory),
      medial prefrontal cortices (cortical control of amygdala responses), and hippocampus.

      Stress responses could partially explain relationships between AI therapy and neural markers
      of cognitive changes. The Mindfulness Stress-Buffering Account suggests that interventions
      such as Mindfulness-Based Stress Reduction (MBSR) may improve stress responses by attenuating
      negative appraisals of stress and reducing reactivity to stressful situations. For example,
      mindfulness meditation improved psychological stress responses in women with breast cancer.
      It improved some measures of cognitive function. Mindfulness practices reduced physiological
      markers of stress responses, including inflammatory markers in women with breast cancer and
      in stressed community adults, as well as cortisol reactivity for breast cancer survivors and
      during chemotherapy for colorectal cancer. Although similar neural deficits as were found in
      the investigators' preliminary work have been shown to improve in stressed adult populations
      using MBSR, it is not known whether the intervention improves neural deficits in women taking
      AI therapy (estrogen, production of which is blocked by AI therapy, is neuroprotective and
      promotes neural plasticity). Genetic variability was previously found to moderate the effect
      of MBSR on self-reported cognitive function. Therefore, it is possible that inter-individual
      variability in the expression of genes involved in stress responses could moderate
      relationships between AI therapy and neural markers of cognitive changes during MBSR. Taken
      together, MBSR may improve neural markers of cognitive changes shown in preliminary work to
      be deficient in postmenopausal women before and during AI therapy for breast cancer by
      targeting stress responses. Changes in these neural markers may correspond to improved
      self-report and neuropsychological measures of cognitive function.

      Hypothesis: Stress reduction, moderated by gene expression, blunts the impact of AI therapy
      on neural markers of cognitive function, thereby improving cognitive function and affect in
      women with breast cancer.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A pilot, single-center randomized controlled trial of the preliminary efficacy of an eight-week, group-based Mindfulness-Based Stress Reduction intervention versus Health Enhancement Program active control (i.e., two groups, parallel design) to improve neural markers of changes in cognitive function in postmenopausal women receiving aromatase inhibitor therapy for breast cancer. Participants will be stratified in a permuted block design by receipt of chemotherapy (i.e., two strata). Data will be collected at up to three time points using a repeated measures design (i.e., pre-intervention, post-intervention, approximately three months after the intervention). The study groups will meet at NYU for MBSR or HEP. Neuropsychological, self-report, and biospecimen data collection will be conducted at the Bluestone Center. Neuroimaging data will be collected at the NYU Center for Brain Imaging.
primary purpose: Supportive Care
masking: Double (Investigator, Outcomes Assessor)
masking description: Participants will complete the baseline assessment and be randomly assigned to study group in a permuted block design stratified by receipt of chemotherapy (i.e., two strata). It will not be possible to blind study participants or interventionists to group assignment. To reduce bias, research staff who conduct assessments, including the PI, will be blinded to group assignment (i.e., single blind). Participants will be reminded not to reveal their group assignment to study staff conducting assessments. The study biostatistician will have no direct contact with study participants and will not be blinded to group assignment. The biostatistician will produce and maintain the randomization codes for the permuted blocks. Randomization may only be unmasked by the biostatistician at the completion of data collection, or for reporting of serious adverse events or unanticipated problems for which it will be essential to provide information to the PI on group assignment.
measure: Functional Neural Activation Parameter Estimate
time frame: baseline, 3 months
description: global maximum cluster-level neural activation during task-based functional magnetic resonance imaging for MBSR group compared to Health Enhancement Program group in a whole-brain analysis; paradigm: Emotional Faces N-Back; conditions: happy face distractors minus no face distractors; value has no minimum or maximum; value has no reference ranges; higher values indicate more neural activation
measure: List Sorting Working Memory Test
time frame: baseline, 6 months
description: from National Institutes of Health (NIH) Toolbox; Age 7+ v2.1; measures working memory; T-score range 23-77; 50 indicates the population mean with a standard deviation of 10; higher scores indicate better working memory performance; scores below 40 suggest cognitive impairment
measure: Flanker Inhibitory Control and Attention Test
time frame: baseline, 6 months
description: from National Institutes of Health (NIH) Toolbox; Age 12+ v2.1; measures attention; T-score range 23-77; 50 indicates the population mean with a standard deviation of 10; higher scores indicate better attention performance; scores below 40 suggest cognitive impairment
measure: Cognitive Function
time frame: baseline, 3 months, 6 months
description: From the Quality of Life in Neurological Disorders (Neuro-QoL) Bank; v2.0; patient-reported outcome; measures executive function and general cognitive concerns; T-score range 17.3-64.2; 50 indicates the population mean with a standard deviation of 10; higher scores indicate better self-reported cognitive function; scores 41-45 suggest mild cognitive impairment, 31-40 suggest moderate cognitive impairment, and 30 or below suggest severe cognitive impairment
measure: Anxiety
time frame: baseline, 3 months, 6 months
description: From the Quality of Life in Neurological Disorders (Neuro-QoL) Bank; v1.0; patient reported outcome; T-score range 36.4-76.8; 50 indicates the population mean with a standard deviation of 10; higher scores indicate worse self-reported anxiety; scores 55-59 suggest mild anxiety, 60-69 suggest moderate anxiety, and 70 or above suggest severe anxiety
measure: Depression
time frame: baseline, 3 months, 6 months
description: From the Quality of Life in Neurological Disorders (Neuro-QoL) Bank; v1.0; patient-reported outcome; measures depressive symptoms; T-score range 36.9-75.0; 50 indicates the population mean with a standard deviation of 10; higher scores indicate worse depressive symptoms; scores 55-59 suggest mild depressive symptoms, 60-69 suggest moderate depressive symptoms, and 70 or above suggest severe depressive symptoms
measure: Gene Expression
time frame: baseline, 3 months, 6 months
description: AMIGO1 gene expression in raw gene counts for MBSR group compared to Health Enhancement Program group in a whole transcriptome analysis using ribonucleic acid sequencing (RNA-Seq); minimum 0, no maximum; value has no reference ranges; higher values indicate more gene expression
arm group label: MBSR
arm group type: Experimental
description: Mindfulness-Based Stress Reduction
arm group label: Health Enhancement Program
arm group type: Active Comparator
description: Health Enhancement Program
intervention type: Behavioral
intervention name: Health Enhancement Program
description: The HEP control, which was developed to serve as an active control to MBSR, will receive manualized health education from experts in physical activity, functional movement, music therapy, and nutrition-without mindfulness instruction-using similar modalities to MBSR training for a matched schedule.
arm group label: Health Enhancement Program
other name: HEP
intervention type: Behavioral
intervention name: Mindfulness-Based Stress Reduction
description: The MBSR group will receive training from a certified instructor during a group-based, 2.5-hour manualized educational activity weekly for eight weeks. Activities include body scans, gentle stretching, yoga, and mindful awareness. Participants will be asked to complete daily 45-minute, audio-guided mindfulness activities and a one-day weekend retreat to reinforce learning.
arm group label: MBSR
other name: MBSR
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 79 Years
healthy volunteers: No
last name: John D Merriman, PhD, RN
role: Principal Investigator
affiliation: New York University Meyers College of Nursing
facility: 
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Neurobehavioral Manifestations
sharing ipd: Yes
ipd description: Even though the R00 study is not anticipated to reach the threshold for required genomic data sharing, the study will have in place plans for sharing de-identified data for secondary analyses with qualified investigators. The consent language for the R00 study will be worded for possible broad data sharing.
ipd time frame: The timeline for submission to an NIH-designated data repository will allow first for publication of findings related to the aims of the R00 study, as well as submission of findings as preliminary data for anticipated grant application(s).
ipd access criteria: The investigators plan to submit genomic data and relevant phenotypic data (e.g., clinical characteristics of the sample) generated in the R00 study to an NIH-designated data repository in a timely manner. The submission process will likely include registration in the database of Genotypes and Phenotypes (dbGaP) and submission to Gene Expression Omnibus (GEO) for controlled access to the data.
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The sample was less than the anticipated final sample size of 32; it included fewer minority participants than planned. The advent of the COVID-19 pandemic prohibited further recruitment and conduct of this study, which had unavoidable in-person activities (e.g., neuroimaging).
point of contact: 