<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/NCT03785223</url>
  </required_header>
  <id_info>
    <org_study_id>5748</org_study_id>
    <nct_id>NCT03785223</nct_id>
  </id_info>
  <brief_title>A 14 Week, Randomized, Placebo-Controlled Cross-Over Study of Methylphenidate Hydrochloride Controlled Release Capsules in Adult ADHD With and Without Anxiety Disorder Comorbidity</brief_title>
  <official_title>A 14 Week, Randomized, Placebo-Controlled Cross-Over Study of Methylphenidate Hydrochloride Controlled Release Capsules in Adult ADHD With and Without Anxiety Disorder Comorbidity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>McMaster University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Purdue Pharma, Canada</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>McMaster 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>
      Other psychiatric disorders, including anxiety, often co-occur with adult ADHD; with 85% of&#xD;
      ADHD patients having at least one other psychiatric condition. The presence of a co-occurring&#xD;
      anxiety disorder has been associated with additive clinical effects, leading to more global&#xD;
      impairment, poorer outcome, greater resistance to treatment and increased costs of illness.&#xD;
      Stimulants are effective first-line treatments for adult ADHD patients, however the&#xD;
      literature has mostly examined these treatments in pure ADHD populations (i.e. without other&#xD;
      psychiatric disorders). Thus, there is little information to guide physicians in making&#xD;
      treatment decisions for patients with ADHD and a co-occurring condition.&#xD;
&#xD;
      This trial aims to evaluate the efficacy and safety of methylphenidate hydrochloride&#xD;
      controlled release capsules (Foquest) in treating adults aged 18-65 years with DSM-5 ADHD&#xD;
      with and without a co-occurring anxiety disorder.The study uses a 14-week, randomized,&#xD;
      placebo-controlled, cross-over design.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 20, 2019</start_date>
  <completion_date type="Anticipated">March 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">February 28, 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Attention Deficit and Hyperactivity Rating Scale - 5</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The ADHD-RS-5 is a scale for children and adolescents that assesses the frequency and severity of ADHD symptoms and impairments based on criteria from the Diagnostic Statistics Manual 5. The measure will be adapted for use with adults as a clinician rated scale in this study. It consists of 18 items, rated on a 4-point scale from 0 (never or rarely) to 3 (very often). The items can be summed to obtain a total score (range: 0-54), an Inattention subscore (range:0-27), and a Hyperactivity-Impulsivity subscore (range: 0-27), with higher scores indicating greater frequency and severity of symptoms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hamilton Anxiety Rating Scale (HAM-A)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The 14-item HAM-A was developed to assess general anxiety symptoms in a clinical population and has proven sensitive to change with treatment. It is a clinician-rated measure and will be administered by a trained, blinded rater, using the Structured Interview Guide for the HAM-A. It has 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) are summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicates less anxiety.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression - Severity (CGI-S)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The CGI-S is a clinician-rated instrument used to assess global severity of symptoms. The CGI-S ranges from 1 (normal, not ill) to 7 (among the most severely ill).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression - Improvement (CGI-I)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The CGI-I is a clinician-rated instrument used to assess overall improvement of illness. The CGI-I ranges from 1 (very much improved) to 7 (very much worse).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Montgomery-Åsberg Depression Rating Scale (MADRS)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The MADRS is a clinician rated scale evaluating depressive symptoms. It consists of 10 items assessed on a 7-point scale (range: 0-6). The total score ranges from 0 to 60, with higher scores indicating greater severity of depressive symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Barkley Adult ADHD Rating Scale (BAARS-IV)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>Self-report scale evaluating ADHD symptoms. Symptom count scores range from 1 to 27, with higher scores indicating more ADHD symptoms. Total scores range from 27 to 108, with higher scores indicating greater severity of symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weiss Functional Impairment Rating Scale-Self Report (WFIRS-S)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The WFRIS is a self-reported measure of functional impairment associated with ADHD in various clinically-relevant domains of functioning. It examines both symptoms and behviours or emotional problems that may have impacted each functioning in each domain. It consists of 70 items, rated on a 4-point scale from 0 (never or not at all) to 3 (very often or very much). Total scores range from 0 to 210, with higher scores indicative of greater ADHD-related functional impairment. Subscores may be calculated for specific domains by summing the items within that section: family (range: 0-24), work (range: 0-33), school (range: 0-33), life skills (range: 0-36), self-concept (range: 0-15), social (range: 0-27), and risk (range: 0-42).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Barkley Deficits in Executive Functioning Scale (BDEFS)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The BDEFS is an adult self-report measure of executive functioning skills in daily life activities. It contains 20 items assessed on a 4-point scale ranging from 1 (never or rarely) to 4 (very often). The total score ranges from 20-80, with higher scores indicating greater deficit in executive functioning skills relevant to daily activities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Anxiety Severity and Impairment Scale (OASIS)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The OASIS is a self-report measure assessing the severity and impairment associated with anxiety disorders. It contains 5 items rated on a 5-point scale (range: 0-4). The total score ranges from 0-20, with greater scores indicating greater severity of anxiety and related impairment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Obsessive Compulsive Inventory - Revised (OCI-R)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The OCI-R is a self-report scale for assessing symptoms of Obsessive-Compulsive Disorder (OCD). It consists of 18 questions with a 5-point scale (range: 0 to 4). The possible range of scores is 0 to 72, with higher scores indicating a greater likelihood of the presence of OCD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quick Inventory of Depressive Symptoms (QID-SR-16)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The QIDS is a self-report measure of depression. It contains 16 items with a 4-point scale (range: 0 to 3) which assess the severity of the nine diagnostic symptom criteria used in the DSM: Sleep disturbance, sad mood, decrease/increase in appetite/weight, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, and psychomotor agitation/retardation. The total possible score is ranged from 0 to 27, with higher scores representing greater severity of depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sheehan Disability Scale (SDS)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The SDS is a 3 question instrument designed to assess functional impairment associated with mental disorders in three domains: work impairment, social impairment, and impairment of family life or home responsibilities. Each sub-scale score ranges from 0 to 10 and a total disability score, calculated as the sum of scores for each question ranges from 0 to 30. Higher scores reflect greater impairment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Social Phobia Inventory (SPIN)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The SPIN is a self-report questionnaire measuring the severity of social anxiety symptoms. It consists of 17 items assessed on a 5-point scale, ranging from 0 (not at all) to 4 (extremely). The total possible score ranges from 0-68, with higher scores representing greater severity of social anxiety symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Generalized Anxiety Disorder-7</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The GAD-7 is a self-reported questionnaire that measures the severity of various signs of GAD. It contains seven items with a 4-point scale (range: 0 to 3). The total possible score is ranged from 0 to 21, with higher scores representing greater severity of GAD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Panic and Agoraphobia Scale (PAS)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The PAS is a measure of the severity of illness in patients with panic disorder (with or without agoraphobia). It has 13 items with a 5-point scale (range: 0-4). The total possible score is ranged from 0 to 52, with higher scores representing increased severity of illness. It contains 5 sub-scales: panic attacks, agoraphobic avoidance, anticipatory anxiety, disability, and functional avoidance (health concerns).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PTSD Checklist for DSM-5 (PCL-5)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The PCL-5 is a 20 item self-report measure that assesses symptoms of PTSD. Each item is rated on a 5-point scale from 0 (not at all) to 4 (extremely). The possible range of scores is 0 to 80, with higher scores indicating greater severity of PTSD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drug Abuse Screening Test (DAST)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The DAST is a self-report measure used to identify individuals that are abusing drugs (not including alcohol). It contains 20 items requiring a &quot;yes&quot; or &quot;no&quot; response, of which &quot;yes&quot; is scored as 1 and &quot;no&quot; is scored as 0 for 18 items, and &quot;yes&quot; is scored as 0 and &quot;no&quot; is scored as 1 for 2 items. The total score ranges from 0-20, with higher scores indicated a greater degree of drug use and misuse issues.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alcohol Use Disorders Identification Test (AUDIT)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The AUDIT is a self-report screening test that assesses alcohol consumption, drinking behaviours, and alcohol-related problems. It consists of 20 items, 8 of which are rated on a 4-point scale from 0-4, and 2 of which are rated on a 3-point scale from 0, 2 and 4. The items are summed to obtain a total score ranging from 0-40, with higher scores indicating a greater degree of risky drinking. Consumption and dependance subscores (range: 0-12) may also be calculated by summing specific items.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cannabis Use Disorder Identification Test-Revised (CUDIT-R)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The CUDIT-R is a self-report screening test that assesses cannabis use and related problems. It contains 8 items, 7 of which are rated on a 5-point scale ranging from 0 (never) to 4 (daily or almost daily), and 1 of which is rated on a 3-point scale from 0, 2 and 4. The total score ranges from 0-32, with higher scores indicating more hazardous cannabis use.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hoarding Rating Scale (HRS)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The HRS will be administered as a self-report questionnaire to assess hoarding symptoms. It consists of 5 items rated on a 9-point scale from 0 (none) to 8 (extreme). The total scores range from 0-40, with greater scores indicating greater hoarding severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Binge Eating Scale (BES)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The BES is a self-report measure of behaviours, cognitions, and emotions related to binge eating. It consists of 16 items, 14 of which are rated on a 4-point scale from 0-3, and 2 of which are rated on a 3-point scale from 0-2. The total score ranges from 0-46, with higher scores indicating more severe binge eating problems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pittsburgh Sleep Quality Index (PSQI)</measure>
    <time_frame>Change from baseline to Week 12</time_frame>
    <description>The PSQI is a self-report questionnaire which measures sleep quality, patterns, and disturbances. It consists of 9 items, 4 of which are rated on a 4-point scale of 0 (not during the past month) to 3 (3 or more times a week), and 1 of which is rated on a 4 point scale of 0 (very good) to 3 (very bad). The other 4 questions collect information on sleep time and duration. The items are summed to produce 7 component scores ranging from 0-3, which are subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction. These component scores are then combined to get the total score ranging from 0-21, with higher scores indicating worse sleep quality.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Attention Deficit Hyperactivity Disorder</condition>
  <condition>Generalized Anxiety Disorder</condition>
  <condition>Social Anxiety Disorder</condition>
  <condition>Panic Disorder</condition>
  <condition>Agoraphobia</condition>
  <arm_group>
    <arm_group_label>Methylphenidate Hydrochloride Controlled-Release Capsules</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Flexibly dosed at 25-100 mg per day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Capsules</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>1-4 capsules daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylphenidate Hydrochloride Controlled-Release Capsules</intervention_name>
    <description>25 mg methylphenidate hydrochloride- titrated as tolerated up to a maximum 4 capsules daily (25 mg- 100 mg total dose)&#xD;
At Week 0 or Week 7, dosing will start at 1 capsule/day for one week, and be titrated to 2 capsules/day for Week 2. 50 mg of methylphenidate hydrochloride per day (i.e. 2 capsules/day) is the minimum dose that must be achieved. The dose may be titrated to 75 mg/day for Week 3 and to 100 mg/day for Week 4 if participants are tolerating their current dose, are experiencing no adverse events, and have not fully responded. By Week 4 or Week 11, no further dose changes will occur.</description>
    <arm_group_label>Methylphenidate Hydrochloride Controlled-Release Capsules</arm_group_label>
    <other_name>Foquest</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Capsule</intervention_name>
    <description>At Week 0 or Week 7, dosing will start at 1 capsule/day for one week, and be titrated to 2 capsules/day for Week 2. The dose may be titrated to 75 mg/day for Week 3 and to 100 mg/day for Week 4 if participants are tolerating their current dose, are experiencing no adverse events, and have not fully responded. By Week 4 or Week 11 no further dose changes will occur.</description>
    <arm_group_label>Placebo Capsules</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Outpatient men and women between 18 and 65 years who meet criteria for Current DSM-5&#xD;
             ADHDalone or with one of the following DSM-5 diagnoses: GAD, SAD,PD or Agoraphobia.&#xD;
             Major Depressive Disorder or Persistent Depressive Disorder will be allowed, providing&#xD;
             the severity is considered moderate or less, as defined by a score on the Montgomery&#xD;
             Depressive Rating Scale-MADRS score of ≤ 25.&#xD;
&#xD;
          2. ADHD rating scale for DSM-5 (ADHD-5-RS) score ≥ 24.&#xD;
&#xD;
          3. Concomitant treatment with selective serotonin reuptake inhibitors (SSRI's), serotonin&#xD;
             noradrenaline reuptake inhibitors (SNRI's), benzodiazepines, beta-blockers, atypical&#xD;
             anti-psychotics, anti-epileptics is allowed, provided the dose has been stable for 8&#xD;
             weeks prior to study entry. Dose changes of allowed concomitant medication should be&#xD;
             avoided during the treatment phases of the study.&#xD;
&#xD;
          4. The ability to comprehend and satisfactorily comply with protocol requirements.&#xD;
&#xD;
          5. Written informed consent given prior to entering the baseline period of the study.&#xD;
&#xD;
          6. All women of child bearing potential must have a negative screening visit serum or&#xD;
             urine pregnancy test and be using adequate contraception for the duration of the&#xD;
             study. Medically acceptable forms of contraception include oral contraceptives,&#xD;
             injectable or implantable methods, intrauterine devices or properly used barrier&#xD;
             contraception. Additionally, the use of condoms is suggested as an adjunct to the&#xD;
             methods previously addressed to provide additional protection against accidental&#xD;
             pregnancy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participants who currently fulfill criteria for a lifetime history of bipolar&#xD;
             disorder, schizophrenia or other psychotic disorders, delirium, dementia and amnesic&#xD;
             and other cognitive disorders, severe head injury, autism spectrum disorders, or are&#xD;
             in a current agitated state.&#xD;
&#xD;
          2. Participants with a history of seizure disorders, or an unstable medical condition&#xD;
             will also be excluded.&#xD;
&#xD;
          3. Participants with significant suicidal ideation (MADRS item 10 score &gt; 3) or who have&#xD;
             enacted suicidal behaviours within 6 months prior to intake will be excluded from&#xD;
             study participation and referred for appropriate clinical intervention.&#xD;
&#xD;
          4. Current treatment with a stimulant.&#xD;
&#xD;
          5. A history of &gt; 2 failed trials of adequately dosed psychostimulants for Adult ADHD.&#xD;
&#xD;
          6. Patients receiving current psychotherapy, including cognitive behavioural therapy for&#xD;
             either ADHD or an anxiety disorder, within 4 weeks prior to the baseline period.&#xD;
&#xD;
          7. Patients who are known to be allergic to methylphenidate or components of&#xD;
             methylphenidate hydrochloride, have known hypersensitivity or idiosyncrasy to&#xD;
             methylphenidate hydrochloride.&#xD;
&#xD;
          8. Patients who have thyroid pathology, treatment of which has not been stabilized for at&#xD;
             least 3 months.&#xD;
&#xD;
          9. MAO inhibitors within 3 weeks of the start of the baseline.&#xD;
&#xD;
         10. Individuals meeting criteria for current cannabis use disorder or substance use&#xD;
             disorder will be excluded.&#xD;
&#xD;
         11. Current use of bupropion or tri-cyclic antidepressants, with the exception of&#xD;
             clomipramine.&#xD;
&#xD;
         12. Current use of clonidine, modafinil or atomoxetine.&#xD;
&#xD;
         13. Previous intolerance or failure to respond to an adequate trial of methylphenidate&#xD;
             hydrochloride controlled release capsules (defined as a minimum of 55mg per day for at&#xD;
             least 4 weeks).&#xD;
&#xD;
         14. Patients who have a history or evidence of a medical condition that would expose them&#xD;
             to an increase or significant adverse event or interfere with assessments of safety&#xD;
             and efficacy during the course of the trial including: advanced arteriosclerosis,&#xD;
             symptomatic cardiovascular disease, moderate to severe hypertension, or other&#xD;
             pre-existing cardiac abnormalities or other serious cardiac problems.&#xD;
&#xD;
         15. Patients with a history of Glaucoma.&#xD;
&#xD;
         16. Sleep medications during the study period are excluded with the exception of zopiclone&#xD;
             and zolpidem and melatonin.&#xD;
&#xD;
         17. Patients using any herbal psychoactive treatments, eg; St.John's Wort, Valerian, Kava&#xD;
             Kava, or Chamomile Extract within 14 days prior to randomization.&#xD;
&#xD;
         18. Patients who have received electroconvulsive therapy within the previous 6 months.&#xD;
&#xD;
         19. Patients with any condition or on any therapy that in the investigator's opinion or as&#xD;
             indicated in the methylphenidate hydrochlorideproduct label, that may pose a risk to&#xD;
             the subject or interfere with the study objective.&#xD;
&#xD;
         20. Patients having clinically significant abnormal laboratory or ECG findings not&#xD;
             resolved by the baseline examination.&#xD;
&#xD;
         21. Patients with a proximal family history of sudden, unexplained cardiac death.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Van Ameringen, MD, FRCPC</last_name>
    <role>Principal Investigator</role>
    <affiliation>McMaster University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Beth Patterson, MSc</last_name>
    <phone>289-396-4242</phone>
    <email>bpatter@mcmaster.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>MacAnxiety Research Center</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8S 1B7</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Beth Patterson, MSc</last_name>
      <phone>905-921-7644</phone>
      <email>bpatter@mcmaster.ca</email>
    </contact>
    <investigator>
      <last_name>Michael Van Ameringen, MD, FRCPC</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Arun Ravindran, MBBS, PhD, FRCPC, FRCPsych</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>December 20, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>August 31, 2020</last_update_submitted>
  <last_update_submitted_qc>August 31, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>ADHD</keyword>
  <keyword>Anxiety Disorders</keyword>
  <keyword>Stimulants</keyword>
  <keyword>Methylphenidate</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anxiety Disorders</mesh_term>
    <mesh_term>Attention Deficit Disorder with Hyperactivity</mesh_term>
    <mesh_term>Panic Disorder</mesh_term>
    <mesh_term>Phobia, Social</mesh_term>
    <mesh_term>Agoraphobia</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>Undecided</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/NCT03785223
org study id: 5748
nct id: NCT03785223
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Other psychiatric disorders, including anxiety, often co-occur with adult ADHD; with 85% of
      ADHD patients having at least one other psychiatric condition. The presence of a co-occurring
      anxiety disorder has been associated with additive clinical effects, leading to more global
      impairment, poorer outcome, greater resistance to treatment and increased costs of illness.
      Stimulants are effective first-line treatments for adult ADHD patients, however the
      literature has mostly examined these treatments in pure ADHD populations (i.e. without other
      psychiatric disorders). Thus, there is little information to guide physicians in making
      treatment decisions for patients with ADHD and a co-occurring condition.

      This trial aims to evaluate the efficacy and safety of methylphenidate hydrochloride
      controlled release capsules (Foquest) in treating adults aged 18-65 years with DSM-5 ADHD
      with and without a co-occurring anxiety disorder.The study uses a 14-week, randomized,
      placebo-controlled, cross-over design.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Attention Deficit and Hyperactivity Rating Scale - 5
time frame: Change from baseline to Week 12
description: The ADHD-RS-5 is a scale for children and adolescents that assesses the frequency and severity of ADHD symptoms and impairments based on criteria from the Diagnostic Statistics Manual 5. The measure will be adapted for use with adults as a clinician rated scale in this study. It consists of 18 items, rated on a 4-point scale from 0 (never or rarely) to 3 (very often). The items can be summed to obtain a total score (range: 0-54), an Inattention subscore (range:0-27), and a Hyperactivity-Impulsivity subscore (range: 0-27), with higher scores indicating greater frequency and severity of symptoms.
measure: Hamilton Anxiety Rating Scale (HAM-A)
time frame: Change from baseline to Week 12
description: The 14-item HAM-A was developed to assess general anxiety symptoms in a clinical population and has proven sensitive to change with treatment. It is a clinician-rated measure and will be administered by a trained, blinded rater, using the Structured Interview Guide for the HAM-A. It has 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) are summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicates less anxiety.
measure: Clinical Global Impression - Severity (CGI-S)
time frame: Change from baseline to Week 12
description: The CGI-S is a clinician-rated instrument used to assess global severity of symptoms. The CGI-S ranges from 1 (normal, not ill) to 7 (among the most severely ill).
measure: Clinical Global Impression - Improvement (CGI-I)
time frame: Change from baseline to Week 12
description: The CGI-I is a clinician-rated instrument used to assess overall improvement of illness. The CGI-I ranges from 1 (very much improved) to 7 (very much worse).
measure: Montgomery-Åsberg Depression Rating Scale (MADRS)
time frame: Change from baseline to Week 12
description: The MADRS is a clinician rated scale evaluating depressive symptoms. It consists of 10 items assessed on a 7-point scale (range: 0-6). The total score ranges from 0 to 60, with higher scores indicating greater severity of depressive symptoms.
measure: Barkley Adult ADHD Rating Scale (BAARS-IV)
time frame: Change from baseline to Week 12
description: Self-report scale evaluating ADHD symptoms. Symptom count scores range from 1 to 27, with higher scores indicating more ADHD symptoms. Total scores range from 27 to 108, with higher scores indicating greater severity of symptoms.
measure: Weiss Functional Impairment Rating Scale-Self Report (WFIRS-S)
time frame: Change from baseline to Week 12
description: The WFRIS is a self-reported measure of functional impairment associated with ADHD in various clinically-relevant domains of functioning. It examines both symptoms and behviours or emotional problems that may have impacted each functioning in each domain. It consists of 70 items, rated on a 4-point scale from 0 (never or not at all) to 3 (very often or very much). Total scores range from 0 to 210, with higher scores indicative of greater ADHD-related functional impairment. Subscores may be calculated for specific domains by summing the items within that section: family (range: 0-24), work (range: 0-33), school (range: 0-33), life skills (range: 0-36), self-concept (range: 0-15), social (range: 0-27), and risk (range: 0-42).
measure: Barkley Deficits in Executive Functioning Scale (BDEFS)
time frame: Change from baseline to Week 12
description: The BDEFS is an adult self-report measure of executive functioning skills in daily life activities. It contains 20 items assessed on a 4-point scale ranging from 1 (never or rarely) to 4 (very often). The total score ranges from 20-80, with higher scores indicating greater deficit in executive functioning skills relevant to daily activities.
measure: Overall Anxiety Severity and Impairment Scale (OASIS)
time frame: Change from baseline to Week 12
description: The OASIS is a self-report measure assessing the severity and impairment associated with anxiety disorders. It contains 5 items rated on a 5-point scale (range: 0-4). The total score ranges from 0-20, with greater scores indicating greater severity of anxiety and related impairment.
measure: Obsessive Compulsive Inventory - Revised (OCI-R)
time frame: Change from baseline to Week 12
description: The OCI-R is a self-report scale for assessing symptoms of Obsessive-Compulsive Disorder (OCD). It consists of 18 questions with a 5-point scale (range: 0 to 4). The possible range of scores is 0 to 72, with higher scores indicating a greater likelihood of the presence of OCD.
measure: Quick Inventory of Depressive Symptoms (QID-SR-16)
time frame: Change from baseline to Week 12
description: The QIDS is a self-report measure of depression. It contains 16 items with a 4-point scale (range: 0 to 3) which assess the severity of the nine diagnostic symptom criteria used in the DSM: Sleep disturbance, sad mood, decrease/increase in appetite/weight, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, and psychomotor agitation/retardation. The total possible score is ranged from 0 to 27, with higher scores representing greater severity of depression.
measure: Sheehan Disability Scale (SDS)
time frame: Change from baseline to Week 12
description: The SDS is a 3 question instrument designed to assess functional impairment associated with mental disorders in three domains: work impairment, social impairment, and impairment of family life or home responsibilities. Each sub-scale score ranges from 0 to 10 and a total disability score, calculated as the sum of scores for each question ranges from 0 to 30. Higher scores reflect greater impairment.
measure: Social Phobia Inventory (SPIN)
time frame: Change from baseline to Week 12
description: The SPIN is a self-report questionnaire measuring the severity of social anxiety symptoms. It consists of 17 items assessed on a 5-point scale, ranging from 0 (not at all) to 4 (extremely). The total possible score ranges from 0-68, with higher scores representing greater severity of social anxiety symptoms.
measure: Generalized Anxiety Disorder-7
time frame: Change from baseline to Week 12
description: The GAD-7 is a self-reported questionnaire that measures the severity of various signs of GAD. It contains seven items with a 4-point scale (range: 0 to 3). The total possible score is ranged from 0 to 21, with higher scores representing greater severity of GAD.
measure: Panic and Agoraphobia Scale (PAS)
time frame: Change from baseline to Week 12
description: The PAS is a measure of the severity of illness in patients with panic disorder (with or without agoraphobia). It has 13 items with a 5-point scale (range: 0-4). The total possible score is ranged from 0 to 52, with higher scores representing increased severity of illness. It contains 5 sub-scales: panic attacks, agoraphobic avoidance, anticipatory anxiety, disability, and functional avoidance (health concerns).
measure: PTSD Checklist for DSM-5 (PCL-5)
time frame: Change from baseline to Week 12
description: The PCL-5 is a 20 item self-report measure that assesses symptoms of PTSD. Each item is rated on a 5-point scale from 0 (not at all) to 4 (extremely). The possible range of scores is 0 to 80, with higher scores indicating greater severity of PTSD.
measure: Drug Abuse Screening Test (DAST)
time frame: Change from baseline to Week 12
description: The DAST is a self-report measure used to identify individuals that are abusing drugs (not including alcohol). It contains 20 items requiring a "yes" or "no" response, of which "yes" is scored as 1 and "no" is scored as 0 for 18 items, and "yes" is scored as 0 and "no" is scored as 1 for 2 items. The total score ranges from 0-20, with higher scores indicated a greater degree of drug use and misuse issues.
measure: Alcohol Use Disorders Identification Test (AUDIT)
time frame: Change from baseline to Week 12
description: The AUDIT is a self-report screening test that assesses alcohol consumption, drinking behaviours, and alcohol-related problems. It consists of 20 items, 8 of which are rated on a 4-point scale from 0-4, and 2 of which are rated on a 3-point scale from 0, 2 and 4. The items are summed to obtain a total score ranging from 0-40, with higher scores indicating a greater degree of risky drinking. Consumption and dependance subscores (range: 0-12) may also be calculated by summing specific items.
measure: Cannabis Use Disorder Identification Test-Revised (CUDIT-R)
time frame: Change from baseline to Week 12
description: The CUDIT-R is a self-report screening test that assesses cannabis use and related problems. It contains 8 items, 7 of which are rated on a 5-point scale ranging from 0 (never) to 4 (daily or almost daily), and 1 of which is rated on a 3-point scale from 0, 2 and 4. The total score ranges from 0-32, with higher scores indicating more hazardous cannabis use.
measure: Hoarding Rating Scale (HRS)
time frame: Change from baseline to Week 12
description: The HRS will be administered as a self-report questionnaire to assess hoarding symptoms. It consists of 5 items rated on a 9-point scale from 0 (none) to 8 (extreme). The total scores range from 0-40, with greater scores indicating greater hoarding severity.
measure: Binge Eating Scale (BES)
time frame: Change from baseline to Week 12
description: The BES is a self-report measure of behaviours, cognitions, and emotions related to binge eating. It consists of 16 items, 14 of which are rated on a 4-point scale from 0-3, and 2 of which are rated on a 3-point scale from 0-2. The total score ranges from 0-46, with higher scores indicating more severe binge eating problems.
measure: Pittsburgh Sleep Quality Index (PSQI)
time frame: Change from baseline to Week 12
description: The PSQI is a self-report questionnaire which measures sleep quality, patterns, and disturbances. It consists of 9 items, 4 of which are rated on a 4-point scale of 0 (not during the past month) to 3 (3 or more times a week), and 1 of which is rated on a 4 point scale of 0 (very good) to 3 (very bad). The other 4 questions collect information on sleep time and duration. The items are summed to produce 7 component scores ranging from 0-3, which are subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction. These component scores are then combined to get the total score ranging from 0-21, with higher scores indicating worse sleep quality.
arm group label: Methylphenidate Hydrochloride Controlled-Release Capsules
arm group type: Experimental
description: Flexibly dosed at 25-100 mg per day
arm group label: Placebo Capsules
arm group type: Placebo Comparator
description: 1-4 capsules daily
intervention type: Drug
intervention name: Methylphenidate Hydrochloride Controlled-Release Capsules
description: 25 mg methylphenidate hydrochloride- titrated as tolerated up to a maximum 4 capsules daily (25 mg- 100 mg total dose)
At Week 0 or Week 7, dosing will start at 1 capsule/day for one week, and be titrated to 2 capsules/day for Week 2. 50 mg of methylphenidate hydrochloride per day (i.e. 2 capsules/day) is the minimum dose that must be achieved. The dose may be titrated to 75 mg/day for Week 3 and to 100 mg/day for Week 4 if participants are tolerating their current dose, are experiencing no adverse events, and have not fully responded. By Week 4 or Week 11, no further dose changes will occur.
arm group label: Methylphenidate Hydrochloride Controlled-Release Capsules
other name: Foquest
intervention type: Drug
intervention name: Placebo Capsule
description: At Week 0 or Week 7, dosing will start at 1 capsule/day for one week, and be titrated to 2 capsules/day for Week 2. The dose may be titrated to 75 mg/day for Week 3 and to 100 mg/day for Week 4 if participants are tolerating their current dose, are experiencing no adverse events, and have not fully responded. By Week 4 or Week 11 no further dose changes will occur.
arm group label: Placebo Capsules
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Michael Van Ameringen, MD, FRCPC
role: Principal Investigator
affiliation: McMaster University
last name: Beth Patterson, MSc
phone: 289-396-4242
email: bpatter@mcmaster.ca
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Canada
responsible party type: Sponsor
mesh term: Anxiety Disorders
mesh term: Attention Deficit Disorder with Hyperactivity
mesh term: Panic Disorder
mesh term: Phobia, Social
mesh term: Agoraphobia
mesh term: Methylphenidate
sharing ipd: Undecided