<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/NCT02970500</url>
  </required_header>
  <id_info>
    <org_study_id>2016-MPH-02-3006</org_study_id>
    <nct_id>NCT02970500</nct_id>
  </id_info>
  <brief_title>Effect of Methylphenidate on Cancer-related Cognitive Impairment</brief_title>
  <acronym>CogMet</acronym>
  <official_title>Étude Pilote de Phase II Sur l'Effet du méthylphénidate Sur la Fonction Cognitive Des Patientes en rémission d'un Cancer du Sein</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CHU de Quebec-Universite Laval</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Équipe de Recherche Michel-Sarrazin en Oncologie psychosociale et Soins palliatifs</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Purdue Pharma LP</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fondation de l'Hôtel-Dieu de Lévis</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>CHU de Quebec-Universite Laval</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>
      Cancer-related cognitive Impairment (CRCI), commonly referred to as &quot;chemo brain&quot; or &quot;brain&#xD;
      fog&quot;-impact severely on the Quality of Life (QoL) of cancer survivors. However, it still&#xD;
      remains underdiagnosed and challenging to treat. One of the treatment options is the use of&#xD;
      psychostimulants such as Methylphenidate (MP), but well-designed clinical trials to test its&#xD;
      efficacy are limited. We will conduct a phase II study with a mixed method design to explore&#xD;
      the preliminary efficacy of MP to improve cognitive function and QoL in breast cancer&#xD;
      patients after treatment with chemotherapy and/or radiotherapy and determine the parameters&#xD;
      needed for designing a phase III study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objectives: The main objective of this study is to determine the parameters for a phase III&#xD;
      study to measure the efficacy of MP in improving CRCI in women with breast cancer who&#xD;
      received chemotherapy and/or radiotherapy. In addition, the profile of drug side effects will&#xD;
      be estimated. A better understanding of CRCI and its impact on the activities and QoL of the&#xD;
      study population is targeted.&#xD;
&#xD;
      Population: The sample will consist of 40 women in remission of non-metastatic breast cancer&#xD;
      whose profile meets the following criteria:&#xD;
&#xD;
        1. receiving follow-up at the radio-oncology department of the CHU de Québec-Université&#xD;
           Laval or at any other health institutions in Quebec participating in the project;&#xD;
&#xD;
        2. complaining about cognitive impairment;&#xD;
&#xD;
        3. not having any contraindications to the taking of MP or any medical condition that may&#xD;
           interfere with his taking and/or any medical condition that could explain the cognitive&#xD;
           impairment.&#xD;
&#xD;
      Before study inclusion, the eligibility of these women will be validated by questionnaires&#xD;
      and medical records.&#xD;
&#xD;
      Study design: This study will follow the design of a randomized, double-blind,&#xD;
      placebo-controlled trial that includes a mixed methodology (convergent design).&#xD;
&#xD;
      Procedures: The study will be divided into two phases. The first phase will start at time T0,&#xD;
      before any MP is taken, and will last 14 days (T1). Participants will be assigned to the&#xD;
      intervention group, where they will receive 10 mg of MP controlled-release (SR) for 14 days,&#xD;
      or the control group where they will receive an identical placebo capsule for 14 days. The&#xD;
      second phase begins at T1 and ends 14 days later (T2). This phase will explore a higher&#xD;
      dosage. Participants from the intervention group during phase 1 will received an increased&#xD;
      dose of MP (20 mg - two capsules) during 14 days whereas participants from the control group&#xD;
      will receive two placebo capsules during 14 days.&#xD;
&#xD;
      Measures: Quantitative data. Questionnaires and tests will be used. The effect size&#xD;
      calculation will be based on the 'Perceived Cognitive Impairments' (PCI) subscale of the&#xD;
      Functional Assessment of Cancer Therapy-Cognitive Function questionnaire (FACT-Cog) test and&#xD;
      will be used to determine the required power for a phase III study. Other tests will be&#xD;
      explored to assess the sensitivity to measure cognitive changes. Descriptive statistical&#xD;
      analysis will be performed. Tests such as the T-Test, χ2 and ANOVA will be used to estimate&#xD;
      the degree of improvement of cognitive function by comparing data of the different groups.&#xD;
      Qualitative data. Interviews will be conducted with the 40 women included in the study. These&#xD;
      interviews will focus on their experience of cognitive deficits before and after taking&#xD;
      MP/Placebo at T0 and T2. In order to document the experience of these women and to assess the&#xD;
      transferability of the resutls, two methods will be combined to analyze these interviews: an&#xD;
      intra-case analysis and an inter-case analysis. Each of the components of the study will&#xD;
      answer its main questions independently. However, the data will also be matched&#xD;
      (triangulation) to provide a global understanding of the issue and convergence of results&#xD;
      when possible.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    We decided to close recruitment in December 2022 as we were having trouble recruiting&#xD;
    participants who met our inclusion criteria and the study funding was coming to an end.&#xD;
  </why_stopped>
  <start_date type="Actual">October 9, 2017</start_date>
  <completion_date type="Actual">December 31, 2022</completion_date>
  <primary_completion_date type="Actual">December 31, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in cognitive impairment level</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>'Perceived Cognitive Impairments' (PCI) subscale of the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire (FACT-Cog) test</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Methylphenidate side effects</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Tracking and registration of methylphenidate side effects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Methylphenidate effect on fatigue</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Fatigue evaluation with a validated questionnaire: Multidimensional Fatigue Inventory (MFI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Experience of women with cancer-related cognitive impairment in cancer</measure>
    <time_frame>Up to 24 months</time_frame>
    <description>Semi-structured interviews</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Breast Cancer Female</condition>
  <condition>Cancer-Related Condition</condition>
  <arm_group>
    <arm_group_label>Methylphenidate HCl 10Mg SR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants of the intervention group (n=20) will receive 1 capsule of Methylphenidate HCl 10 mg SR each morning during 14 days during phase 1 and 2 capsules of Methylphenidate HCl 10 mg SR each morning during 14 days during phase 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants of the control group (n=20) will receive 1 capsule of placebo each morning during 14 days during phase 1 and 2 capsules of placebo each morning during 14 days during phase 2.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylphenidate HCl 10Mg SR</intervention_name>
    <description>Methylphenidate HCl 10Mg SR (Phase 1) and Methylphenidate HCl 20Mg SR (Phase 2)</description>
    <arm_group_label>Methylphenidate HCl 10Mg SR</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Group</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Breast cancer stage I, II or III&#xD;
&#xD;
          2. Completed chemotherapy and/or radiotherapy at least 6 months before entering the study&#xD;
&#xD;
          3. Being in remission of breast cancer&#xD;
&#xD;
          4. Complaining of cognitive impairment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Current or recent use (&lt;2 years) of psychostimulant drugs&#xD;
&#xD;
          2. Women receiving drugs with a potential of interaction with methylphenidate:&#xD;
&#xD;
             i. Anticoagulants; ii. Antidepressants with the exception of: amitriptyline (≤75mg);&#xD;
             citalopram (≤40mg); desipramine (≤75mg); duloxetine (≤60mg); escitalopram (≤20mg);&#xD;
             fluoxetine (≤60mg); fluvoxamine (≤150mg); mirtazapine (≤60mg); nortriptyline (≤50mg);&#xD;
             trazadone (≤50mg); venlafaxine (≤150mg); vortioxetine (≤20mg); iii. Drugs (cocaine);&#xD;
             iv. Erythropoietin; v. Drugs acting on the cerebral dopaminergic system, including&#xD;
             drugs that inhibit monoamine oxidase; vi. John's wort, natural medicines for&#xD;
             depression or supplements for fatigue.&#xD;
&#xD;
          3. Conditions that may increase the risk of cognitive impairment or toxicity of&#xD;
             methylphenidate such as:&#xD;
&#xD;
             i. Pregnancy and breastfeeding ii. Bipolar status iii. Cerebral tumor or any brain&#xD;
             injury iv. Metastatic cancer v. Alcohol addiction vi. Active Major depression vii.&#xD;
             Parkinson disease viii. Dementia ix. Epilepsia x. Glaucoma xi. Cardiovascular diseases&#xD;
             xii. Auto-immunes and chronic inflammatory disease xiii. Cerebrovascular disease xiv.&#xD;
             Narcolepsy xv. Pheochromocytoma xvi. Thyrotoxicosis xvii. Motor tic, Tourette syndrome&#xD;
             xviii. Generalized anxiety disorder or panic attacks xix. Living under the same roof&#xD;
             as people taking Biphentin® 10 mg capsules (this exclusion criteria is necessary&#xD;
             because the placebo capsule is identical to the commercial formulation of Biphentin®)&#xD;
             xx. Any other medical criteria, according to the clinical judgment of the principal&#xD;
             investigator.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bruno Gagnon</last_name>
    <role>Principal Investigator</role>
    <affiliation>Laval University, Centre de recherche du CHU de Québec</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Hôtel-Dieu de Lévis</name>
      <address>
        <city>Lévis</city>
        <state>Quebec</state>
        <zip>G6V 3Z1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre de recherche du CHU de QUébec</name>
      <address>
        <city>Quebec</city>
        <zip>G1R 2J6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>November 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2016</study_first_posted>
  <last_update_submitted>March 21, 2023</last_update_submitted>
  <last_update_submitted_qc>March 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>CHU de Quebec-Universite Laval</investigator_affiliation>
    <investigator_full_name>Dr Bruno Gagnon</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Cognitive impairment</keyword>
  <keyword>Methylphenidate</keyword>
  <keyword>Cancer-related cognitive impairment</keyword>
  <keyword>Mixed method</keyword>
  <keyword>Phase II study</keyword>
  <keyword>Breast cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylphenidate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02970500
org study id: 2016-MPH-02-3006
nct id: NCT02970500
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Cancer-related cognitive Impairment (CRCI), commonly referred to as "chemo brain" or "brain
      fog"-impact severely on the Quality of Life (QoL) of cancer survivors. However, it still
      remains underdiagnosed and challenging to treat. One of the treatment options is the use of
      psychostimulants such as Methylphenidate (MP), but well-designed clinical trials to test its
      efficacy are limited. We will conduct a phase II study with a mixed method design to explore
      the preliminary efficacy of MP to improve cognitive function and QoL in breast cancer
      patients after treatment with chemotherapy and/or radiotherapy and determine the parameters
      needed for designing a phase III study.
Objectives: The main objective of this study is to determine the parameters for a phase III
      study to measure the efficacy of MP in improving CRCI in women with breast cancer who
      received chemotherapy and/or radiotherapy. In addition, the profile of drug side effects will
      be estimated. A better understanding of CRCI and its impact on the activities and QoL of the
      study population is targeted.

      Population: The sample will consist of 40 women in remission of non-metastatic breast cancer
      whose profile meets the following criteria:

        1. receiving follow-up at the radio-oncology department of the CHU de Québec-Université
           Laval or at any other health institutions in Quebec participating in the project;

        2. complaining about cognitive impairment;

        3. not having any contraindications to the taking of MP or any medical condition that may
           interfere with his taking and/or any medical condition that could explain the cognitive
           impairment.

      Before study inclusion, the eligibility of these women will be validated by questionnaires
      and medical records.

      Study design: This study will follow the design of a randomized, double-blind,
      placebo-controlled trial that includes a mixed methodology (convergent design).

      Procedures: The study will be divided into two phases. The first phase will start at time T0,
      before any MP is taken, and will last 14 days (T1). Participants will be assigned to the
      intervention group, where they will receive 10 mg of MP controlled-release (SR) for 14 days,
      or the control group where they will receive an identical placebo capsule for 14 days. The
      second phase begins at T1 and ends 14 days later (T2). This phase will explore a higher
      dosage. Participants from the intervention group during phase 1 will received an increased
      dose of MP (20 mg - two capsules) during 14 days whereas participants from the control group
      will receive two placebo capsules during 14 days.

      Measures: Quantitative data. Questionnaires and tests will be used. The effect size
      calculation will be based on the 'Perceived Cognitive Impairments' (PCI) subscale of the
      Functional Assessment of Cancer Therapy-Cognitive Function questionnaire (FACT-Cog) test and
      will be used to determine the required power for a phase III study. Other tests will be
      explored to assess the sensitivity to measure cognitive changes. Descriptive statistical
      analysis will be performed. Tests such as the T-Test, χ2 and ANOVA will be used to estimate
      the degree of improvement of cognitive function by comparing data of the different groups.
      Qualitative data. Interviews will be conducted with the 40 women included in the study. These
      interviews will focus on their experience of cognitive deficits before and after taking
      MP/Placebo at T0 and T2. In order to document the experience of these women and to assess the
      transferability of the resutls, two methods will be combined to analyze these interviews: an
      intra-case analysis and an inter-case analysis. Each of the components of the study will
      answer its main questions independently. However, the data will also be matched
      (triangulation) to provide a global understanding of the issue and convergence of results
      when possible.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in cognitive impairment level
time frame: Up to 24 months
description: 'Perceived Cognitive Impairments' (PCI) subscale of the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire (FACT-Cog) test
measure: Methylphenidate side effects
time frame: Up to 24 months
description: Tracking and registration of methylphenidate side effects
measure: Methylphenidate effect on fatigue
time frame: Up to 24 months
description: Fatigue evaluation with a validated questionnaire: Multidimensional Fatigue Inventory (MFI)
measure: Experience of women with cancer-related cognitive impairment in cancer
time frame: Up to 24 months
description: Semi-structured interviews
arm group label: Methylphenidate HCl 10Mg SR
arm group type: Experimental
description: Participants of the intervention group (n=20) will receive 1 capsule of Methylphenidate HCl 10 mg SR each morning during 14 days during phase 1 and 2 capsules of Methylphenidate HCl 10 mg SR each morning during 14 days during phase 2.
arm group label: Placebo Group
arm group type: Placebo Comparator
description: Participants of the control group (n=20) will receive 1 capsule of placebo each morning during 14 days during phase 1 and 2 capsules of placebo each morning during 14 days during phase 2.
intervention type: Drug
intervention name: Methylphenidate HCl 10Mg SR
description: Methylphenidate HCl 10Mg SR (Phase 1) and Methylphenidate HCl 20Mg SR (Phase 2)
arm group label: Methylphenidate HCl 10Mg SR
intervention type: Drug
intervention name: Placebo Group
description: Placebo
arm group label: Placebo Group
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Bruno Gagnon
role: Principal Investigator
affiliation: Laval University, Centre de recherche du CHU de Québec
facility: 
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: CHU de Quebec-Universite Laval
investigator full name: Dr Bruno Gagnon
investigator title: Associate Professor
mesh term: Cognitive Dysfunction
mesh term: Methylphenidate
sharing ipd: No