<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/NCT03306979</url>
  </required_header>
  <id_info>
    <org_study_id>241-2017</org_study_id>
    <nct_id>NCT03306979</nct_id>
  </id_info>
  <brief_title>Memory and Antioxidants in Vascular Impairment Trial</brief_title>
  <official_title>Efficacy and Safety of N-acetylcysteine (NAC) in Patients With Mild Vascular Cognitive Impairment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sunnybrook Health Sciences Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sunnybrook Health Sciences Centre</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a 24-week randomized, double-blind, placebo-controlled parallel group design study&#xD;
      involving Vascular cognitive impairment-no dementia (VCIND) patients to evaluate the efficacy&#xD;
      and safety of oral NAC supplementation (2,400 mg daily) as an add-on therapy to improve&#xD;
      cognitive function in patients undergoing cardiac rehabilitation (CR). The CR program&#xD;
      consists of a harmonized aerobic and resistance training in a supervised group setting.&#xD;
      Eligible patients will be randomized to receive NAC (four 600 mg capsules given as 2 capsules&#xD;
      in the morning and 2 capsules in the evening) or matching placebo capsules. The initial NAC&#xD;
      dosage will be 600mg/day (one 600mg capsule in the morning) for the first week, followed by&#xD;
      1,200 mg/day (one 600 mg capsule in the morning, one 600mg capsule in the evening) for the&#xD;
      second week, followed by 1,800 mg/day (two 600mg capsules in the morning, one 600mg capsule&#xD;
      in the evening) for third week, followed by 2,400mg/day (two 600mg capsules in the morning,&#xD;
      two 600mg capsules in the evening) for the following 21 weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 30, 2018</start_date>
  <completion_date type="Anticipated">December 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2023</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in executive function</measure>
    <time_frame>6 months</time_frame>
    <description>Differences in executive function composite z scores between experimental and placebo groups at 6 months. Executive function will be based on the trail test B found in the 60-minute battery recommended by the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) harmonized standards.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in processing speed</measure>
    <time_frame>6 months</time_frame>
    <description>Differences in processing speed composite z scores between experimental and placebo groups at 6 months. Processing speed will be based on the symbol digit modalities test found in the 60-minute battery recommended by the NINDS-CSN.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in memory</measure>
    <time_frame>6 months</time_frame>
    <description>Differences in memory composite z scores between experimental and placebo groups at 6 months. Memory will be based on the Rey Complex Figure Test found in the 60-minute battery recommended by the NINDS-CSN.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Vascular Cognitive Impairment no Dementia</condition>
  <arm_group>
    <arm_group_label>N-acetylcysteine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants randomized into the N-acetylcysteine arm will be receiving N-acetylcysteine for 24 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants randomized into the placebo arm will be receiving placebo for 24 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>N Acetylcysteine</intervention_name>
    <description>Patients will be randomized to receive N Acetylcysteine (NAC) (four 600 mg capsules given as 2 capsules in the morning and 2 capsules in the evening). The initial NAC dosage will be 600mg/day (one 600mg capsule in the morning) for the first week, followed by 1,200 mg/day (one 600 mg capsule in the morning, one 600mg capsule in the evening) for the second week, followed by 1,800 mg/day (two 600mg capsules in the morning, one 600mg capsule in the evening) for third week, followed by 2,400mg/day (two 600mg capsules in the morning, two 600mg capsules in the evening) for the following 21 weeks.</description>
    <arm_group_label>N-acetylcysteine</arm_group_label>
    <other_name>NPN 80004844</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>Patients will receive four placebo capsules (lactose-based filler) given as 2 capsules in the morning and 2 capsules in the evening, which will be prepared to mimic the weight of the experimental capsules.The initial placebo dosage will be 600mg/day (one 600mg capsule in the morning) for the first week, followed by 1,200 mg/day (one 600 mg capsule in the morning, one 600mg capsule in the evening) for the second week, followed by 1,800 mg/day (two 600mg capsules in the morning, one 600mg capsule in the evening) for third week, followed by 2,400mg/day (two 600mg capsules in the morning, two 600mg capsules in the evening) for the following 21 weeks.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males or females aged 55-80 years.&#xD;
&#xD;
          -  MoCA score of less than 28.&#xD;
&#xD;
          -  Modest deficits (1 SD below population norm) in executive function, memory, processing&#xD;
             speed, or working memory based on the 60-minute battery recommended by the NINDS-CSN.&#xD;
&#xD;
          -  Speaks and understands English.&#xD;
&#xD;
          -  Enrollment in the Cardiac Rehabilitation program at the University Health Network&#xD;
             Toronto Rehabilitation Institute.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A history of stroke&#xD;
&#xD;
          -  A history of epilepsy&#xD;
&#xD;
          -  Uncontrolled asthma (requiring hospitalization or ER visit in the last 3 months by&#xD;
             patient report)&#xD;
&#xD;
          -  Uncontrolled diabetes (clinical determination)&#xD;
&#xD;
          -  Severe hypo/hypertension (clinical determination)&#xD;
&#xD;
          -  Uncontrolled hypercholesterolemia (clinical determination)&#xD;
&#xD;
          -  Presence of significant medical illnesses (Severely disturbed liver function, Severely&#xD;
             disturbed kidney function, Severely disturbed lung function, HIV, HBV and/or HCV&#xD;
             infection, Malignant tumors)&#xD;
&#xD;
          -  A current neurological condition (Parkinson's disease, Multiple sclerosis, Significant&#xD;
             traumatic brain injury)&#xD;
&#xD;
          -  Major psychiatric condition (Current major depressive disorder, Schizophrenia, Bipolar&#xD;
             disorder, Substance use disorder (alcohol abuse, heavy smoking (20 cigarettes or&#xD;
             more/day))&#xD;
&#xD;
          -  Contraindication to MRI or MRS (e.g. metal in body, pacemaker).&#xD;
&#xD;
          -  Contraindication to NAC (documented allergy) or allergy to lactose.&#xD;
&#xD;
          -  Daily Nitroglycerin use.&#xD;
&#xD;
          -  Bleeding disorders (e.g. hemophilia, Thrombotic Thrombocytopenic Purpura) and/or&#xD;
             elective surgery within 30 days.&#xD;
&#xD;
          -  Volunteers who currently participate in another pharmacological study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Krista L Lanctôt, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sunnybrook Research Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Krista L Lanctôt, PhD</last_name>
    <phone>416-480-6100</phone>
    <phone_ext>2241</phone_ext>
    <email>krista.lanctot@sunnybrook.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jane Ding</last_name>
      <phone>416-480-6100</phone>
      <phone_ext>63185</phone_ext>
      <email>jane.ding@sunnybrook.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>October 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 11, 2017</study_first_posted>
  <last_update_submitted>February 6, 2023</last_update_submitted>
  <last_update_submitted_qc>February 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</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>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetylcysteine</mesh_term>
    <mesh_term>N-monoacetylcystine</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/NCT03306979
org study id: 241-2017
nct id: NCT03306979
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a 24-week randomized, double-blind, placebo-controlled parallel group design study
      involving Vascular cognitive impairment-no dementia (VCIND) patients to evaluate the efficacy
      and safety of oral NAC supplementation (2,400 mg daily) as an add-on therapy to improve
      cognitive function in patients undergoing cardiac rehabilitation (CR). The CR program
      consists of a harmonized aerobic and resistance training in a supervised group setting.
      Eligible patients will be randomized to receive NAC (four 600 mg capsules given as 2 capsules
      in the morning and 2 capsules in the evening) or matching placebo capsules. The initial NAC
      dosage will be 600mg/day (one 600mg capsule in the morning) for the first week, followed by
      1,200 mg/day (one 600 mg capsule in the morning, one 600mg capsule in the evening) for the
      second week, followed by 1,800 mg/day (two 600mg capsules in the morning, one 600mg capsule
      in the evening) for third week, followed by 2,400mg/day (two 600mg capsules in the morning,
      two 600mg capsules in the evening) for the following 21 weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in executive function
time frame: 6 months
description: Differences in executive function composite z scores between experimental and placebo groups at 6 months. Executive function will be based on the trail test B found in the 60-minute battery recommended by the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) harmonized standards.
measure: Change in processing speed
time frame: 6 months
description: Differences in processing speed composite z scores between experimental and placebo groups at 6 months. Processing speed will be based on the symbol digit modalities test found in the 60-minute battery recommended by the NINDS-CSN.
measure: Change in memory
time frame: 6 months
description: Differences in memory composite z scores between experimental and placebo groups at 6 months. Memory will be based on the Rey Complex Figure Test found in the 60-minute battery recommended by the NINDS-CSN.
arm group label: N-acetylcysteine
arm group type: Active Comparator
description: Participants randomized into the N-acetylcysteine arm will be receiving N-acetylcysteine for 24 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants randomized into the placebo arm will be receiving placebo for 24 weeks.
intervention type: Drug
intervention name: N Acetylcysteine
description: Patients will be randomized to receive N Acetylcysteine (NAC) (four 600 mg capsules given as 2 capsules in the morning and 2 capsules in the evening). The initial NAC dosage will be 600mg/day (one 600mg capsule in the morning) for the first week, followed by 1,200 mg/day (one 600 mg capsule in the morning, one 600mg capsule in the evening) for the second week, followed by 1,800 mg/day (two 600mg capsules in the morning, one 600mg capsule in the evening) for third week, followed by 2,400mg/day (two 600mg capsules in the morning, two 600mg capsules in the evening) for the following 21 weeks.
arm group label: N-acetylcysteine
other name: NPN 80004844
intervention type: Other
intervention name: Placebo oral capsule
description: Patients will receive four placebo capsules (lactose-based filler) given as 2 capsules in the morning and 2 capsules in the evening, which will be prepared to mimic the weight of the experimental capsules.The initial placebo dosage will be 600mg/day (one 600mg capsule in the morning) for the first week, followed by 1,200 mg/day (one 600 mg capsule in the morning, one 600mg capsule in the evening) for the second week, followed by 1,800 mg/day (two 600mg capsules in the morning, one 600mg capsule in the evening) for third week, followed by 2,400mg/day (two 600mg capsules in the morning, two 600mg capsules in the evening) for the following 21 weeks.
arm group label: Placebo
other name: Placebo
criteria: 
gender: All
minimum age: 55 Years
maximum age: 85 Years
healthy volunteers: No
last name: Krista L Lanctôt, PhD
role: Principal Investigator
affiliation: Sunnybrook Research Institute
last name: Krista L Lanctôt, PhD
phone: 416-480-6100
phone ext: 2241
email: krista.lanctot@sunnybrook.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Sponsor
mesh term: Cognitive Dysfunction
mesh term: Acetylcysteine
mesh term: N-monoacetylcystine