<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/NCT03772834</url>
  </required_header>
  <id_info>
    <org_study_id>2018-0559</org_study_id>
    <secondary_id>NCI-2018-02527</secondary_id>
    <secondary_id>2018-0559</secondary_id>
    <nct_id>NCT03772834</nct_id>
  </id_info>
  <brief_title>Methylphenidate and Exercise in Reducing Cancer-Related Fatigue in Patients With Prostate Cancer</brief_title>
  <official_title>A Combination Therapy to Treat Cancer-Related Fatigue - NCI R01</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>M.D. Anderson Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>M.D. Anderson 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 phase II/III trial studies how well methylphenidate and exercise work in reducing&#xD;
      cancer-related fatigue in patients with prostate cancer. Methylphenidate is a type of central&#xD;
      nervous system stimulant that can improve cognitive ability, mainly in memory and cognitive&#xD;
      function. Exercise can improve mood and the physical aspects of cancer-related fatigue.&#xD;
      Giving methylphenidate in combination with exercise may work better in reducing&#xD;
      cancer-related fatigue in patients with prostate cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To determine if the combination of exercise (EX) plus methylphenidate (MP) is superior to&#xD;
      exercise plus placebo in the treatment of cancer-related fatigue (CRF) in patients with&#xD;
      prostate cancer scheduled to receive radiotherapy with androgen deprivation therapy for 12&#xD;
      weeks.&#xD;
&#xD;
      SECONDARY OBJECTIVE:&#xD;
&#xD;
      I. To determine the effects of combined exercise plus methylphenidate on quality-of-life,&#xD;
      mood, physical, and cognitive measures.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To identify potential synergistic effects of exercise and methylphenidate in improvement&#xD;
      of CRF.&#xD;
&#xD;
      II. To explore changes in brain activity by electroencephalography (EEG) in responders (with&#xD;
      4 point or greater change in Functional Assessment of Chronic Illness Therapy-Fatigue&#xD;
      [FACIT-F] scores) versus (vs) non-responders to the intervention.&#xD;
&#xD;
      OUTLINE: Patients are randomized to 1 of 4 groups.&#xD;
&#xD;
      GROUP I: Patients receive methylphenidate orally (PO) twice daily (BID) and undergo exercise&#xD;
      program consisting of resistance training twice weekly (BIW) and walking 15- 40 minutes a day&#xD;
      4 days a week for 12 weeks.&#xD;
&#xD;
      GROUP II: Patients receive a placebo PO BID and undergo exercise program consisting of&#xD;
      resistance training BIW and walking 15-40 minutes a day for 4 days a week for 12 weeks.&#xD;
&#xD;
      GROUP III: Patients receive methylphenidate PO BID and undergo stretching for 4 days a week&#xD;
      for 12 weeks.&#xD;
&#xD;
      GROUP IV: Patients receive a placebo PO BID and undergo stretching for 4 days a week for 12&#xD;
      weeks.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 3 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 25, 2019</start_date>
  <completion_date type="Anticipated">November 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2023</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Supportive Care</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Level of cancer-related fatigue in all groups</measure>
    <time_frame>Up to 12 weeks</time_frame>
    <description>Will measure cancer-related fatigue (CRF) using the area under the curve (AUC) of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale score. The intervention exposure will be operationalized as proportion of the total minutes of prescribed exercise intervention the study patient was actually able to participate, or the proportion of prescribed study medication the study patient was able to actually take.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life, mood, physical and cognitive measures in all groups</measure>
    <time_frame>Baseline up to 12 weeks</time_frame>
    <description>Will use a mixed-effects model to compare changes in Functional Assessment of Cancer Therapy - General (FACT-G), Pittsburgh Sleep Quality Index (PSQI), Multidimensional Fatigue Symptom Inventory - Short Form (MFSI-SF), Hospital Anxiety and Depression Scale (HADS), usual gait speed, hand grip strength (HGS), 30 second chair stand test (30s-CST), actigraphy, VO2 max, and C-reactive protein scores over time between the four treatment groups. For the mixed effects model, we will estimate the slopes for the changes in scores over time for each group and test the difference in these slopes.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Synergistic effects of methylphenidate and exercise in all groups</measure>
    <time_frame>Up to 12 weeks</time_frame>
    <description>Will measure the synergistic effects of methylphenidate and exercise in improving CRF using the AUC of the FACIT-F subscale score. The analysis will be conducted using a linear model with the AUC as the response variable and indicator variables for the exercise and methylphenidate main effects as well as a product term of these indicator variables to assess the magnitude of synergy.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in brain activity by electroencephalography (EEG) in responders versus non-responders as measured by the FACIT-F score</measure>
    <time_frame>Baseline up to 12 weeks</time_frame>
    <description>Responders are identified as those who report a 4 point or greater change, while non-responders report less than a 4 point change in the FACIT-F score. EEG data will be grouped according to response status. Between-group differences will be examined using univariate analysis of variance (ANOVA) with condition (responders or non-responders) as the fixed factor of interest, and the change of power from baseline to the resting state EEG at day 29 and day 84 as the dependent variable. Additional analyses will include analysis of covariance (ANCOVA) by adjusting for baseline covariates including age, stage of disease, total dose of radiotherapy, and other covariates as necessary.</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">354</enrollment>
  <condition>Prostate Carcinoma</condition>
  <arm_group>
    <arm_group_label>Group I (methylphenidate, resistance training, walking)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive methylphenidate PO BID and undergo exercise program consisting of resistance training BIW and walking 15- 40 minutes a day 4 days a week for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group II (placebo, resistance training, stretching)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive a placebo PO BID and undergo exercise program consisting of resistance training BIW and walking 15-40 minutes a day for 4 days a week for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group III (methylphenidate, stretching)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive methylphenidate PO BID and undergo stretching for 4 days a week for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group IV (placebo, stretching)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive a placebo PO BID and undergo stretching for 4 days a week for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Exercise Intervention</intervention_name>
    <description>Undergo resistance training and walking</description>
    <arm_group_label>Group I (methylphenidate, resistance training, walking)</arm_group_label>
    <arm_group_label>Group II (placebo, resistance training, stretching)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylphenidate</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Group I (methylphenidate, resistance training, walking)</arm_group_label>
    <arm_group_label>Group III (methylphenidate, stretching)</arm_group_label>
    <other_name>Daytrana</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Group II (placebo, resistance training, stretching)</arm_group_label>
    <arm_group_label>Group IV (placebo, stretching)</arm_group_label>
    <other_name>placebo therapy</other_name>
    <other_name>PLCB</other_name>
    <other_name>sham therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Quality-of-Life Assessment</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Group I (methylphenidate, resistance training, walking)</arm_group_label>
    <arm_group_label>Group II (placebo, resistance training, stretching)</arm_group_label>
    <arm_group_label>Group III (methylphenidate, stretching)</arm_group_label>
    <arm_group_label>Group IV (placebo, stretching)</arm_group_label>
    <other_name>Quality of Life Assessment</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaire Administration</intervention_name>
    <description>Ancillary studies</description>
    <arm_group_label>Group I (methylphenidate, resistance training, walking)</arm_group_label>
    <arm_group_label>Group II (placebo, resistance training, stretching)</arm_group_label>
    <arm_group_label>Group III (methylphenidate, stretching)</arm_group_label>
    <arm_group_label>Group IV (placebo, stretching)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Stretching</intervention_name>
    <description>Undergo stretching</description>
    <arm_group_label>Group III (methylphenidate, stretching)</arm_group_label>
    <arm_group_label>Group IV (placebo, stretching)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have a diagnosis of prostate cancer and be scheduled to receive radiotherapy with&#xD;
             concurrent androgen deprivation therapy, and presence of fatigue with severity of&#xD;
             1/10, on a 0-10 scale for at least 2 weeks&#xD;
&#xD;
          -  Patient not regularly engaging in moderate aerobic exercise for &gt;90 minutes/week&#xD;
             and/or vigorous aerobic exercise for &gt;30 minutes/week, and/ or strength training for&#xD;
             &gt;/= 1 day/week&#xD;
&#xD;
          -  Have no clinical evidence of cognitive failure as evidenced by Memorial Delirium&#xD;
             Assessment Scale score of &lt;/=13 at baseline&#xD;
&#xD;
          -  Be aged 18 years or older&#xD;
&#xD;
          -  Be willing to engage in follow-up telephone calls with a research staff&#xD;
&#xD;
          -  Be willing to participate in the exercise programs&#xD;
&#xD;
          -  Have telephone access so they can be contacted by the research staff&#xD;
&#xD;
          -  Have a hemoglobin level of &gt;/= 10 g/dL within 2 weeks of enrollment&#xD;
&#xD;
          -  Be able to understand the description of the study and give written informed consent&#xD;
&#xD;
          -  Have a Zubrod performance status score of 0 to 2&#xD;
&#xD;
          -  Seen at an outpatient clinic at MD Anderson Cancer Center, its Houston Area Locations&#xD;
             (HALs) or Smith Radiation Oncology Clinic (HHS)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have a major contraindication to MethylphenidateMP) (e.g., allergy/hypersensitivity to&#xD;
             study medications or their constituents), exercise (e.g., cardiac disease), or&#xD;
             conditions making adherence difficult as determined by the attending physician&#xD;
&#xD;
          -  Be currently taking MP, or have taken it within the previous 10 days&#xD;
&#xD;
          -  Be unable to complete the baseline assessment forms (e.g., due to language or sensory&#xD;
             barriers) or to understand the recommendations for participation in the study&#xD;
&#xD;
          -  Need monoamine oxidase inhibitors, tricyclic antidepressants, or clonidine&#xD;
&#xD;
          -  Have glaucoma&#xD;
&#xD;
          -  Have severe cardiac disease (New York Heart Association functional class III or IV)&#xD;
&#xD;
          -  Have tachycardia and/or uncontrolled hypertension&#xD;
&#xD;
          -  Be currently receiving anticoagulants, anticonvulsants (phenobarbital,&#xD;
             diphenylhydantone, primidone), phenylbutazone, and/or tricyclic drugs (imipramine,&#xD;
             clomipramine, or desipramine).&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sriram Yennu</last_name>
    <role>Principal Investigator</role>
    <affiliation>M.D. Anderson Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sriram Yennu</last_name>
    <phone>713-792-6085</phone>
    <email>syennu@mdanderson.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sriram Yennu</last_name>
      <phone>713-792-6085</phone>
    </contact>
    <investigator>
      <last_name>Sriram Yennu</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mdanderson.org</url>
    <description>MD Anderson Cancer Center Website</description>
  </link>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>December 7, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <last_update_submitted>September 21, 2022</last_update_submitted>
  <last_update_submitted_qc>September 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 22, 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>Prostatic Neoplasms</mesh_term>
    <mesh_term>Fatigue</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylphenidate</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03772834
org study id: 2018-0559
secondary id: NCI-2018-02527
secondary id: 2018-0559
nct id: NCT03772834
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II/III trial studies how well methylphenidate and exercise work in reducing
      cancer-related fatigue in patients with prostate cancer. Methylphenidate is a type of central
      nervous system stimulant that can improve cognitive ability, mainly in memory and cognitive
      function. Exercise can improve mood and the physical aspects of cancer-related fatigue.
      Giving methylphenidate in combination with exercise may work better in reducing
      cancer-related fatigue in patients with prostate cancer.
PRIMARY OBJECTIVE:

      I. To determine if the combination of exercise (EX) plus methylphenidate (MP) is superior to
      exercise plus placebo in the treatment of cancer-related fatigue (CRF) in patients with
      prostate cancer scheduled to receive radiotherapy with androgen deprivation therapy for 12
      weeks.

      SECONDARY OBJECTIVE:

      I. To determine the effects of combined exercise plus methylphenidate on quality-of-life,
      mood, physical, and cognitive measures.

      EXPLORATORY OBJECTIVES:

      I. To identify potential synergistic effects of exercise and methylphenidate in improvement
      of CRF.

      II. To explore changes in brain activity by electroencephalography (EEG) in responders (with
      4 point or greater change in Functional Assessment of Chronic Illness Therapy-Fatigue
      [FACIT-F] scores) versus (vs) non-responders to the intervention.

      OUTLINE: Patients are randomized to 1 of 4 groups.

      GROUP I: Patients receive methylphenidate orally (PO) twice daily (BID) and undergo exercise
      program consisting of resistance training twice weekly (BIW) and walking 15- 40 minutes a day
      4 days a week for 12 weeks.

      GROUP II: Patients receive a placebo PO BID and undergo exercise program consisting of
      resistance training BIW and walking 15-40 minutes a day for 4 days a week for 12 weeks.

      GROUP III: Patients receive methylphenidate PO BID and undergo stretching for 4 days a week
      for 12 weeks.

      GROUP IV: Patients receive a placebo PO BID and undergo stretching for 4 days a week for 12
      weeks.

      After completion of study treatment, patients are followed up at 3 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Double (Participant, Investigator)
measure: Level of cancer-related fatigue in all groups
time frame: Up to 12 weeks
description: Will measure cancer-related fatigue (CRF) using the area under the curve (AUC) of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale score. The intervention exposure will be operationalized as proportion of the total minutes of prescribed exercise intervention the study patient was actually able to participate, or the proportion of prescribed study medication the study patient was able to actually take.
measure: Change in quality of life, mood, physical and cognitive measures in all groups
time frame: Baseline up to 12 weeks
description: Will use a mixed-effects model to compare changes in Functional Assessment of Cancer Therapy - General (FACT-G), Pittsburgh Sleep Quality Index (PSQI), Multidimensional Fatigue Symptom Inventory - Short Form (MFSI-SF), Hospital Anxiety and Depression Scale (HADS), usual gait speed, hand grip strength (HGS), 30 second chair stand test (30s-CST), actigraphy, VO2 max, and C-reactive protein scores over time between the four treatment groups. For the mixed effects model, we will estimate the slopes for the changes in scores over time for each group and test the difference in these slopes.
measure: Synergistic effects of methylphenidate and exercise in all groups
time frame: Up to 12 weeks
description: Will measure the synergistic effects of methylphenidate and exercise in improving CRF using the AUC of the FACIT-F subscale score. The analysis will be conducted using a linear model with the AUC as the response variable and indicator variables for the exercise and methylphenidate main effects as well as a product term of these indicator variables to assess the magnitude of synergy.
measure: Change in brain activity by electroencephalography (EEG) in responders versus non-responders as measured by the FACIT-F score
time frame: Baseline up to 12 weeks
description: Responders are identified as those who report a 4 point or greater change, while non-responders report less than a 4 point change in the FACIT-F score. EEG data will be grouped according to response status. Between-group differences will be examined using univariate analysis of variance (ANOVA) with condition (responders or non-responders) as the fixed factor of interest, and the change of power from baseline to the resting state EEG at day 29 and day 84 as the dependent variable. Additional analyses will include analysis of covariance (ANCOVA) by adjusting for baseline covariates including age, stage of disease, total dose of radiotherapy, and other covariates as necessary.
arm group label: Group I (methylphenidate, resistance training, walking)
arm group type: Experimental
description: Patients receive methylphenidate PO BID and undergo exercise program consisting of resistance training BIW and walking 15- 40 minutes a day 4 days a week for 12 weeks.
arm group label: Group II (placebo, resistance training, stretching)
arm group type: Active Comparator
description: Patients receive a placebo PO BID and undergo exercise program consisting of resistance training BIW and walking 15-40 minutes a day for 4 days a week for 12 weeks.
arm group label: Group III (methylphenidate, stretching)
arm group type: Active Comparator
description: Patients receive methylphenidate PO BID and undergo stretching for 4 days a week for 12 weeks.
arm group label: Group IV (placebo, stretching)
arm group type: Active Comparator
description: Patients receive a placebo PO BID and undergo stretching for 4 days a week for 12 weeks.
intervention type: Behavioral
intervention name: Exercise Intervention
description: Undergo resistance training and walking
arm group label: Group I (methylphenidate, resistance training, walking)
arm group label: Group II (placebo, resistance training, stretching)
intervention type: Drug
intervention name: Methylphenidate
description: Given PO
arm group label: Group I (methylphenidate, resistance training, walking)
arm group label: Group III (methylphenidate, stretching)
other name: Daytrana
intervention type: Other
intervention name: Placebo
description: Given PO
arm group label: Group II (placebo, resistance training, stretching)
arm group label: Group IV (placebo, stretching)
other name: placebo therapy
other name: PLCB
other name: sham therapy
intervention type: Other
intervention name: Quality-of-Life Assessment
description: Ancillary studies
arm group label: Group I (methylphenidate, resistance training, walking)
arm group label: Group II (placebo, resistance training, stretching)
arm group label: Group III (methylphenidate, stretching)
arm group label: Group IV (placebo, stretching)
other name: Quality of Life Assessment
intervention type: Other
intervention name: Questionnaire Administration
description: Ancillary studies
arm group label: Group I (methylphenidate, resistance training, walking)
arm group label: Group II (placebo, resistance training, stretching)
arm group label: Group III (methylphenidate, stretching)
arm group label: Group IV (placebo, stretching)
intervention type: Other
intervention name: Stretching
description: Undergo stretching
arm group label: Group III (methylphenidate, stretching)
arm group label: Group IV (placebo, stretching)
criteria: 
gender: Male
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sriram Yennu
role: Principal Investigator
affiliation: M.D. Anderson Cancer Center
last name: Sriram Yennu
phone: 713-792-6085
email: syennu@mdanderson.org
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: http://www.mdanderson.org
description: MD Anderson Cancer Center Website
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: Fatigue
mesh term: Methylphenidate