<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/NCT03280251</url>
  </required_header>
  <id_info>
    <org_study_id>2015_81</org_study_id>
    <secondary_id>2016-005131-32</secondary_id>
    <nct_id>NCT03280251</nct_id>
  </id_info>
  <brief_title>Methylphenidate and Cognitive Training in Elderly</brief_title>
  <acronym>PACTE-1</acronym>
  <official_title>Potentiation of Cognitive Functions in Healthy Elderly by Association of Methylphenidate and Cognitive Training: Proof of Concept Study in Order to Develop a Synergic Symptomatic Treatment for the Cognitive Disorders Before Dementia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Lille</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Lille</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Currently, there is no available drug to treat the symptoms of neurodegenerative and vascular&#xD;
      cognitive disorders that affect millions of people worldwide.&#xD;
&#xD;
      Methylphenidate is indicated at high dose (1 mg/kg/day) in children having attention deficit&#xD;
      and hyperactivity disorder (ADHD) and remains the best cognitive enhancer drug at lower dose.&#xD;
      However, there is no proof of efficacy with chronic administration, outside ADHD, and concern&#xD;
      remains about long-term cardiac and vascular risks in elderly and particularly in population&#xD;
      with vascular risk factors and drug abuse in young people. Moreover, the effect appears to be&#xD;
      very limited at the very advanced stage of dementia, for which the neuronal plasticity is too&#xD;
      reduced to expect a benefit of training.&#xD;
&#xD;
      Taken all together, we sought to develop a new paradigm of association of both&#xD;
      pharmacological and non-pharmacological procedure to enhance the neuronal plasticity in order&#xD;
      to expect a persistent effect on slight to mild cognitive disorders with benefit on&#xD;
      ecological test (i.e. driving). Finally, short-term treatment would reduce the safety&#xD;
      concerns.&#xD;
&#xD;
      The concept will be to prove that low dose of methylphenidate associated with active&#xD;
      cognitive training during 6 weeks can improve the cognitive function in healthy aged&#xD;
      volunteers with a persistent effect at 3 months.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 19, 2018</start_date>
  <completion_date type="Anticipated">November 2024</completion_date>
  <primary_completion_date type="Anticipated">November 2024</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 (Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The difference of the average response time to a choice task at inclusion and at the end of treatment (after 6 weeks)</measure>
    <time_frame>6 weeks after the beginning of the treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline the composite cognitive functions</measure>
    <time_frame>Baseline, at 6 weeks, at 12 weeks</time_frame>
    <description>A composite measure of several cognitive functions: attention, executive functions, working memory, verbal and nonverbal episodic memory, visuo-spatial functions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of the results to task on a driving simulator</measure>
    <time_frame>Baseline, at 6 weeks, at 12 weeks</time_frame>
    <description>A composite measure of task on a driving simulator: travel time, speed parameters(average speed, maintaining the target speed) compliance with the instructions and code of the road (number and type of errors), number of cars doubled, reaction time in analytics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Behavior Rating Inventory of Executive Function (BRIEF-A)</measure>
    <time_frame>Baseline, at 6 weeks, at 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Anxiety and Depression scale (HAD)</measure>
    <time_frame>Baseline, at 6 weeks, at 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of undesirable effects of treatment</measure>
    <time_frame>at 2 weeks, at 4 weeks, at 6 weeks, at 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline the parameters of structured cognitive training (CogniPlus®)</measure>
    <time_frame>Baseline, at 6 weeks, at 12 weeks</time_frame>
    <description>A composite measure of parameters following : processing speed, inhibition and working memory resources.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Resting state EEG</measure>
    <time_frame>Baseline, at 6 weeks, at 12 weeks</time_frame>
    <description>EEG with Attentional Network Test and Go / No Go task</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>resting state functional MRI</measure>
    <time_frame>Baseline, at 6 weeks, at 12 weeks</time_frame>
    <description>The changes of resting state functional MRI after treatment and cognitive training</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Methylphenidate and structured cognitive training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Methylphenidate (capsules of Ritaline LP 10) encapsulated, 0,3 mg per kg per day during 6 weeks Structured cognitive training with CogniPlus software, twice per week during 6 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo and structured cognitive training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo, identical capsules to encapsulated MPH, number of capsules per day identical to MPH during 6 weeks Structured cognitive training with CogniPlus software, twice per week during 6 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Methylphenidate and pseudo cognitive training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Methylphenidate (capsules of Ritaline LP 10) encapsulated, 0,3 mg per kg per day during 6 weeks Pseudo cognitive training with 45 minutes documentary videos and 15 minutes quiz, twice per week during 6 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo and pseudo cognitive training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo, identical capsules to encapsulated MPH, number of capsules per day identical to MPH during 6 weeks Pseudo cognitive training with 45 minutes documentary videos and 15 minutes quiz, twice per week during 6 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylphenidate</intervention_name>
    <description>Methylphenidate (capsules of Ritaline LP 10) encapsulated, 0,3 mg per kg per day during 6 weeks</description>
    <arm_group_label>Methylphenidate and pseudo cognitive training</arm_group_label>
    <arm_group_label>Methylphenidate and structured cognitive training</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo, identical capsules to encapsulated MPH, number of capsules per day identical to MPH during 6 weeks</description>
    <arm_group_label>Placebo and pseudo cognitive training</arm_group_label>
    <arm_group_label>Placebo and structured cognitive training</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>CogniPlus software</intervention_name>
    <description>Structured cognitive training with CogniPlus software, twice per week during 6 weeks</description>
    <arm_group_label>Methylphenidate and structured cognitive training</arm_group_label>
    <arm_group_label>Placebo and structured cognitive training</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pseudo cognitive training</intervention_name>
    <description>Pseudo cognitive training with 45 minutes documentary videos and 15 minutes quiz, twice per week during 6 weeks</description>
    <arm_group_label>Methylphenidate and pseudo cognitive training</arm_group_label>
    <arm_group_label>Placebo and pseudo cognitive training</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Without severe chronic neurological or mental or psychiatric pathology&#xD;
&#xD;
          -  Absence of cognitive impairment affecting autonomy (scores on the dementia scale of&#xD;
             Mattis&gt; 130 and the IADL = 4)&#xD;
&#xD;
          -  Right-handed participant&#xD;
&#xD;
          -  Subjects holding driving license B and continuing a driving activity&#xD;
&#xD;
          -  Affiliate or beneficiary of a social security scheme&#xD;
&#xD;
          -  Subject having signed informed consent&#xD;
&#xD;
          -  Subject having agreed to be registered on the National File of Healthy Volunteers&#xD;
&#xD;
          -  Patient willing to comply with all procedures of the study and its duration&#xD;
&#xD;
          -  No planned changes in lifestyle (nutritional and physical, social interactions) during&#xD;
             the life of the protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Administrative reasons: impossibility of receiving informed information, inability to&#xD;
             participate in the whole study, absence of coverage by the social security system,&#xD;
             refusal to sign consent.&#xD;
&#xD;
          -  Subject simultaneously participating in another clinical trial or in an exclusion&#xD;
             period.&#xD;
&#xD;
          -  Subject under tutelage or curatelle.&#xD;
&#xD;
          -  Subject during breastfeeding or pregnancy.&#xD;
&#xD;
          -  Subject not sufficiently fluent in the French language to understand the instructions&#xD;
             necessary to carry out the cognitive tests.&#xD;
&#xD;
          -  Subject with uncorrected visual pathology or motor pathology (orthopedic example)&#xD;
             likely to interfere with the passing of tests.&#xD;
&#xD;
          -  Subject with dependencies pre-existing to medicines, drugs or alcohol.&#xD;
&#xD;
          -  Presence of contraindications to MRI: Claustrophobia, Anxiety crisis, Morphotype not&#xD;
             allowing access to MRI, metal implant (eg a pacemaker), surgical clips Ferromagnetic,&#xD;
             orbital or brain metallic foreign bodies).&#xD;
&#xD;
          -  Hypersensitivity to methylphenidate or any other constituents of the product.&#xD;
&#xD;
          -  Subject with a personal and / or family history of motor tics and Gilles de la&#xD;
             Tourette syndrome.&#xD;
&#xD;
          -  Subjects with a previous psychiatric history (based on the semi-structured psychiatric&#xD;
             interview with the MINI of DSM IV adapted to DSM V): state, severe depression, severe&#xD;
             generalized anxiety, anorexia nervosa or anorexic disorders, suicidal tendencies,&#xD;
             psychotic symptoms, severe mood disorders, mania, schizophrenia, psychopathic&#xD;
             personality disorder or borderline disorder. Dysthymia and an isolated history of&#xD;
             depression do not constitute an exclusion criterion.&#xD;
&#xD;
          -  Subjects consuming one or more psychotropic drugs or related products&#xD;
             (antidepressants, antipsychotics, antiepileptic drugs, daily use of benzodiazepine&#xD;
             anxiolytics or other anxiolytics, vesperal hypnotic intake). A history of taking point&#xD;
             hypnotics is not a criterion of exclusion. However, there should be no regular and&#xD;
             regular intake in the previous 3 months and less than once a week (ideally, lack of&#xD;
             intake would be desirable but would considerably limit the potential for inclusion).&#xD;
             They will be asked not to change their habits during the study period.&#xD;
&#xD;
          -  Subjects with dysthyroidism or thyrotoxicosis&#xD;
&#xD;
          -  Subjects with pre-existing cardiovascular disorders including severe hypertension,&#xD;
             heart failure, occlusive arterial disease, angina pectoris, congenital heart disease&#xD;
             with hemodynamic repercussions, cardiomyopathy, myocardial infarction, arrhythmias and&#xD;
             channelopathies&#xD;
&#xD;
          -  Subject with angle-closure glaucoma.&#xD;
&#xD;
          -  Significant abnormalities on MRI and EEG according to the investigator's judgment&#xD;
&#xD;
          -  Presence of untreated hypertension discovered during screening&#xD;
&#xD;
          -  Subject with pheochromocytoma&#xD;
&#xD;
          -  Pre-existing cerebrovascular disorders, cerebral aneurysm, vascular abnormalities,&#xD;
             including vasculitis or stroke in the subject&#xD;
&#xD;
          -  Subjects with hepatic and renal insufficiency&#xD;
&#xD;
          -  Obese subject according to WHO classification (BMI&gt; 30)&#xD;
&#xD;
          -  Presence of one of the following treatments that cannot be stopped for a period&#xD;
             corresponding to 5 half-lives before inclusion: selective and non-selective MAOIs&#xD;
             (nialamide and iproniazide, selegiline), other indirect sympathomimetics&#xD;
             (phenylpropanolamine, pseudoephedrine, Phenylephrine), halogenated volatile&#xD;
             anesthetics, guanethidine and related compounds.&#xD;
&#xD;
          -  Treatment with alpha sympathomimetics (oral and / or nasal route) (etilefrin,&#xD;
             midodrine, naphazoline, oxymetazoline, tetryzoline, tuaminoheptane, tymazoline),&#xD;
             opiates and morphine derivatives. These concomitant treatments are contraindicated at&#xD;
             baseline and throughout the study period.&#xD;
&#xD;
          -  Subject with leukopathy classified ≥2 on the Fazekas scale&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Devos, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Lille</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>David Devos, MD,PhD</last_name>
    <phone>3 20 44 54 49</phone>
    <phone_ext>+33</phone_ext>
    <email>david.devos@chru-lille.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hôpital Roger Salengro, CHU</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>David DEVOS, MD,PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>August 16, 2022</last_update_submitted>
  <last_update_submitted_qc>August 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cognitive disorders</keyword>
  <keyword>cognitive training</keyword>
  <keyword>symptomatic treatment</keyword>
  <keyword>Methylphenidate</keyword>
  <keyword>elderly</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>
  <!-- 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/NCT03280251
org study id: 2015_81
secondary id: 2016-005131-32
nct id: NCT03280251
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Currently, there is no available drug to treat the symptoms of neurodegenerative and vascular
      cognitive disorders that affect millions of people worldwide.

      Methylphenidate is indicated at high dose (1 mg/kg/day) in children having attention deficit
      and hyperactivity disorder (ADHD) and remains the best cognitive enhancer drug at lower dose.
      However, there is no proof of efficacy with chronic administration, outside ADHD, and concern
      remains about long-term cardiac and vascular risks in elderly and particularly in population
      with vascular risk factors and drug abuse in young people. Moreover, the effect appears to be
      very limited at the very advanced stage of dementia, for which the neuronal plasticity is too
      reduced to expect a benefit of training.

      Taken all together, we sought to develop a new paradigm of association of both
      pharmacological and non-pharmacological procedure to enhance the neuronal plasticity in order
      to expect a persistent effect on slight to mild cognitive disorders with benefit on
      ecological test (i.e. driving). Finally, short-term treatment would reduce the safety
      concerns.

      The concept will be to prove that low dose of methylphenidate associated with active
      cognitive training during 6 weeks can improve the cognitive function in healthy aged
      volunteers with a persistent effect at 3 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Care Provider, Investigator, Outcomes Assessor)
measure: The difference of the average response time to a choice task at inclusion and at the end of treatment (after 6 weeks)
time frame: 6 weeks after the beginning of the treatment
measure: Change from baseline the composite cognitive functions
time frame: Baseline, at 6 weeks, at 12 weeks
description: A composite measure of several cognitive functions: attention, executive functions, working memory, verbal and nonverbal episodic memory, visuo-spatial functions
measure: Change from baseline of the results to task on a driving simulator
time frame: Baseline, at 6 weeks, at 12 weeks
description: A composite measure of task on a driving simulator: travel time, speed parameters(average speed, maintaining the target speed) compliance with the instructions and code of the road (number and type of errors), number of cars doubled, reaction time in analytics.
measure: Behavior Rating Inventory of Executive Function (BRIEF-A)
time frame: Baseline, at 6 weeks, at 12 weeks
measure: Hospital Anxiety and Depression scale (HAD)
time frame: Baseline, at 6 weeks, at 12 weeks
measure: Number of undesirable effects of treatment
time frame: at 2 weeks, at 4 weeks, at 6 weeks, at 12 weeks
measure: Change from baseline the parameters of structured cognitive training (CogniPlus®)
time frame: Baseline, at 6 weeks, at 12 weeks
description: A composite measure of parameters following : processing speed, inhibition and working memory resources.
measure: Resting state EEG
time frame: Baseline, at 6 weeks, at 12 weeks
description: EEG with Attentional Network Test and Go / No Go task
measure: resting state functional MRI
time frame: Baseline, at 6 weeks, at 12 weeks
description: The changes of resting state functional MRI after treatment and cognitive training
arm group label: Methylphenidate and structured cognitive training
arm group type: Experimental
description: Methylphenidate (capsules of Ritaline LP 10) encapsulated, 0,3 mg per kg per day during 6 weeks Structured cognitive training with CogniPlus software, twice per week during 6 weeks
arm group label: Placebo and structured cognitive training
arm group type: Experimental
description: Placebo, identical capsules to encapsulated MPH, number of capsules per day identical to MPH during 6 weeks Structured cognitive training with CogniPlus software, twice per week during 6 weeks
arm group label: Methylphenidate and pseudo cognitive training
arm group type: Experimental
description: Methylphenidate (capsules of Ritaline LP 10) encapsulated, 0,3 mg per kg per day during 6 weeks Pseudo cognitive training with 45 minutes documentary videos and 15 minutes quiz, twice per week during 6 weeks
arm group label: Placebo and pseudo cognitive training
arm group type: Experimental
description: Placebo, identical capsules to encapsulated MPH, number of capsules per day identical to MPH during 6 weeks Pseudo cognitive training with 45 minutes documentary videos and 15 minutes quiz, twice per week during 6 weeks
intervention type: Drug
intervention name: Methylphenidate
description: Methylphenidate (capsules of Ritaline LP 10) encapsulated, 0,3 mg per kg per day during 6 weeks
arm group label: Methylphenidate and pseudo cognitive training
arm group label: Methylphenidate and structured cognitive training
intervention type: Drug
intervention name: Placebo
description: Placebo, identical capsules to encapsulated MPH, number of capsules per day identical to MPH during 6 weeks
arm group label: Placebo and pseudo cognitive training
arm group label: Placebo and structured cognitive training
intervention type: Other
intervention name: CogniPlus software
description: Structured cognitive training with CogniPlus software, twice per week during 6 weeks
arm group label: Methylphenidate and structured cognitive training
arm group label: Placebo and structured cognitive training
intervention type: Other
intervention name: Pseudo cognitive training
description: Pseudo cognitive training with 45 minutes documentary videos and 15 minutes quiz, twice per week during 6 weeks
arm group label: Methylphenidate and pseudo cognitive training
arm group label: Placebo and pseudo cognitive training
criteria: 
gender: All
minimum age: 55 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: David Devos, MD,PhD
role: Principal Investigator
affiliation: University Hospital, Lille
last name: David Devos, MD,PhD
phone: 3 20 44 54 49
phone ext: +33
email: david.devos@chru-lille.fr
facility: 
status: Recruiting
investigator: 
country: France
responsible party type: Sponsor
mesh term: Cognitive Dysfunction
mesh term: Methylphenidate