<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/NCT03252093</url>
  </required_header>
  <id_info>
    <org_study_id>HL131014</org_study_id>
    <secondary_id>1U01HL131014-01A1</secondary_id>
    <nct_id>NCT03252093</nct_id>
  </id_info>
  <brief_title>Evaluation of the Safety and Efficacy of Ang-(1-7) to Enhance Cognitive Function in Participants Undergoing CABG</brief_title>
  <official_title>A Randomized, Placebo-controlled, Double Blind Evaluation of the Safety and Efficacy of Angiotensin 1-7 (Ang-(1-7)) to Enhance Cognitive Function in Participants Undergoing Coronary Artery Bypass Graft (CABG) Surgery.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Arizona</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Suburban Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Arizona</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Coronary Artery Bypass Graft (CABG) is a surgical procedure known to be associated with&#xD;
      cognitive impairment. Mechanisms of cognitive impairment are complex but may include&#xD;
      insufficient oxygenation and inflammation due to exposure to the bypass circuit. Currently&#xD;
      there are no approved therapeutics for the prevention or treatment of cognitive impairment in&#xD;
      these patients.&#xD;
&#xD;
      A small peptide, Angiotensin-(1-7) [Ang-(1-7)], is known to decrease inflammation in the&#xD;
      brain in animal models. Early studies in humans have shown it to be safe. This peptide is&#xD;
      naturally produced by the body and has anti-inflammatory and vasodilatory effects.&#xD;
      Investigators believe that Ang-(1-7) may be able to help lower the risk of cognitive&#xD;
      dysfunction in patients undergoing CABG.&#xD;
&#xD;
      The goal of this project is to explore effects of the experimental peptide Angiotensin-(1-7)&#xD;
      (Ang-(1-7) in patients undergoing an elective CABG surgery to determine its safety and&#xD;
      efficacy to prevent cognitive dysfunction in patients undergoing CABG.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Up to 104 participants (ages 60-80) undergoing elective CABG surgery at the Banner University&#xD;
      Medical Center in Tucson, AZ or at Suburban Hospital/NIH Clinical Center in Bethesda, MD,&#xD;
      will be enrolled in this randomized, placebo-controlled, double-blind study of&#xD;
      Angiotensin-(1-7). Subjects who have a pre-operative neurologic, learning or psychiatric&#xD;
      disorder will be excluded. In addition, a concurrent group of 20 age-matched adults will be&#xD;
      recruited as a neuropsychological control group and will undergo neuropsychological testing&#xD;
      at baseline, Day 21 and Day 90.&#xD;
&#xD;
      Participants will be asked to undergo a screening process to confirm eligibility and to rule&#xD;
      out depression, dementia and contraindications to MRI. Prior to randomization, baseline&#xD;
      measures will include neuropsychological testing, brain MRI, quality of life questionnaires,&#xD;
      inflammatory markers and DNA/RNA sample collection. Participants will be treated for 21 days&#xD;
      with a daily dose of subcutaneous Ang-(1-7) (100 mcg/kg/day) (n=60) or placebo (n=30). These&#xD;
      measures will then be repeated at Day 21 and Day 90. The MRI will be repeated at Day 21 only.&#xD;
&#xD;
      Pharmacokinetic measurements will be obtained prior to administration of Ang-(1-7) or placebo&#xD;
      and hourly for 6 hours following the first 6 doses. Delirium testing will occur on a daily&#xD;
      basis post surgery until discharge. Serum study drug level will be obtained at Day 21.&#xD;
&#xD;
      Lastly, subjects will be followed on a weekly basis by telephone for all 12 weeks of the&#xD;
      study.&#xD;
&#xD;
        1. Primary Objective: To evaluate the safety and tolerability of 21 days of subcutaneous&#xD;
           (s.c.) once daily administration of Ang-(1-7) in eligible participants undergoing&#xD;
           first-time, elective coronary artery bypass graft (CABG) surgery.&#xD;
&#xD;
        2. Secondary Objectives:&#xD;
&#xD;
             1. To determine the pharmacokinetics of 21 days of treatment with Ang-(1-7).&#xD;
&#xD;
             2. To determine if 21 days of treatment with 200 mcg/kg/day of Ang-(1-7) improves&#xD;
                memory function measured as a change in performance from baseline to follow up on a&#xD;
                composite score comprised of memory, executive functioning, language and processing&#xD;
                speed in Ang-(1-7) treatment group compared to placebo controls and non-surgical&#xD;
                controls.&#xD;
&#xD;
             3. To determine if treatment with 200 mcg/kg/day Ang-(1-7) decreases postoperative&#xD;
                delirium length and severity as measured with the Confusion Assessment Method (CAM)&#xD;
                D2 to D7 ( or discharge) after surgery as compared to treatment with placebo group.&#xD;
&#xD;
             4. To determine if 21 days of treatment with 200 mcg/kg/day Ang-(1-7) improves&#xD;
                participant self-reported outcomes using standardized Kansas City Cardiomyopathy&#xD;
                Questionnaire (KCCQ) and Instrumental Activities of Daily Living (IADL) measurement&#xD;
                tools.&#xD;
&#xD;
             5. To determine if 21 days treatment with 200 mcg/kg/day Ang-(1-7) results in changes&#xD;
                in suicidal ideation and behavior as assessed by The Columbia Suicide Severity&#xD;
                Rating Scale (C-SSRS).&#xD;
&#xD;
             6. To compare postoperative mortality and morbidity at 90 days in the 200 mcg/kg/day&#xD;
                Ang-(1-7) treatment group with the placebo group.&#xD;
&#xD;
             7. To determine if 21 days of treatment of 200 mcg/kg/day Ang-(1-7) decreases&#xD;
                postoperative observable changes in brain fractional anisotropy as measured by&#xD;
                diffuse on magnetic resonance imaging (MRI) as compared to placebo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Due to funding&#xD;
  </why_stopped>
  <start_date type="Actual">July 20, 2017</start_date>
  <completion_date type="Anticipated">November 15, 2022</completion_date>
  <primary_completion_date type="Anticipated">November 15, 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>Demonstrate 21 days daily administration of Ang-(1-7) in participants undergoing 1st time CABG surgery is safe and efficacious as assessed by the number of related AEs grade 3 or &gt; and change in composite neuropsychological score up to Day 90.</measure>
    <time_frame>Up to Day 90</time_frame>
    <description>Adverse events (AEs), including serious adverse events (SAEs) will be monitored from the time of enrollment through Day 90. The number of AEs, withdrawals due to AE, and withdrawals for other reasons will be tabulated. Additional assessments include: serum blood levels of the Ang-(1-7) at Day 1, Day 3, Day 5 or Discharge and Day 21. Lastly blood pressuring monitoring pre and post treatment will occur Day 1 to discharge.&#xD;
Change in performance on composite scores of memory, executive functioning, language and processing speed in the treatment arm compared to placebo arm and non-surgical controls measured at 3 time points will assess the effectiveness of Ang-(1-7) in reducing postoperative cognitive impairment in CABG patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Demonstrated change in the neuropsychological component scores assessed at baseline, Day 21 and Day 90 in the treatment and placebo arms.</measure>
    <time_frame>Up to Day 90</time_frame>
    <description>The component scores to be analyzed will include Rey Auditory Verbal Learning Test (RAVLT) and Confusion Assessment Method (CAM), assessment of general intellectual functioning (North American Adult Reading Test), prospective memory (MIST; Memory Intentions Test) , Visual Paired Associates, Object-Spatial Locations, three areas of executive functions including updating (Keep Track), shifting (Letter-Number), and inhibition (Stroop Color-Word), and psychomotor speed (Deary Simple and Complex Reaction Times, Trials A and B).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evidence of change in fractional anisotropy from diffusion tensor imaging on Brain MRI at baseline versus post operative Day 21 will be assessed in the treatment and placebo arms as a measure of efficacy.</measure>
    <time_frame>Up to Day 21</time_frame>
    <description>CABG surgery will result in observable changes in gray matter volumes and integrity of white matter as measured by structural and diffusion MR imaging in all participants. Similar voxel-based multivariate regression analyses will be used for other MRI measures including gray and white matter volumes, axial and radial diffusion, and ASL perfusion. Comparisons between CABG patients and controls will use the general linear model in SPM8 with group (CABG, controls) as a categorical factor and age as a mean-centered control variable. For structural MRI, ICV will also be included as a covariate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Demonstrated change in PBR28 VT/fP, a quantitative measure of TSPO receptor density, in a composite cerebral region-of-interest (ROI) derived from brain PET imaging in the treatment and placebo arms.</measure>
    <time_frame>Up to Day 21</time_frame>
    <description>PBR28 VT/fP will be measured in a composite cerebral region-of-interest (ROI), including automatic anatomically labeled, bilateral medial and lateral temporal, parietal, precuneus, prefrontal ROIs (Reiman, 2009) in the treatment and placebo arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Demonstrated associations between neuropsychogical test results, MRI findings and PBR28 binding in all participants.</measure>
    <time_frame>Up to Day 90</time_frame>
    <description>Neuropsychological testing outcomes and MRI findings will analyzed to evaluate associations between these outcomes and PBR28 binding. In addition, systemic inflammatory markers will be measured, including GM-CSF, IFNγ, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, and TNFα.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Coronary Artery Bypass Surgery</condition>
  <condition>Cognitive Impairment</condition>
  <arm_group>
    <arm_group_label>Angiotensin-(1-7)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intervention: Drug: 200 mcg/kg/day injected subcutaneously once daily for 21 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo for Angiotensin-(1-7)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Intervention: Placebo for Angiotensin-(1-7) injected subcutaneously once daily for 21 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Angiotensin-(1-7)</intervention_name>
    <description>Subcutaneous injection of 200 mcg/kg/day</description>
    <arm_group_label>Angiotensin-(1-7)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo for Angiotensin-(1-7)</intervention_name>
    <description>Subcutaneous injection of Placebo</description>
    <arm_group_label>Placebo for Angiotensin-(1-7)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult male or female first time cardiac surgical participants&#xD;
&#xD;
          -  Elective on pump coronary artery bypass grafting (CABG)&#xD;
&#xD;
          -  Age 60-80&#xD;
&#xD;
          -  Signed, informed consent&#xD;
&#xD;
          -  Geriatric Depression Scale score less than or = 14or Beck's Depression Inventory less&#xD;
             than or = 20&#xD;
&#xD;
          -  Score &gt; or = 25 on the Mini-Mental State Examination (MMSE)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Recent (within 60 days) Cerebrovascular disease with neurological change&#xD;
&#xD;
          -  Malignancy or pre-malignant state within 5 years not including non-melanoma skin&#xD;
             cancer&#xD;
&#xD;
          -  History of liver dysfunction with ongoing sequelae (including but not limited to liver&#xD;
             enzymes &gt; 2.5 x upper limit or normal (ULN) at screening).&#xD;
&#xD;
          -  History of renal dysfunction with ongoing sequelae (including but not limited to&#xD;
             creatinine value &gt; 2.5 mg/dL at screening).&#xD;
&#xD;
          -  Significant Lung Disease (FEV1&lt; 1.5 L, pO2 &lt;70 on room air, pCO2 &gt;45)&#xD;
&#xD;
          -  Presence of any severe mental illness that could affect interpretation of efficacy&#xD;
             data, such as schizophrenia or bipolar affective disorder; any untreated or unstable&#xD;
             psychiatric condition including depressive disorder or anxiety disorder.&#xD;
&#xD;
          -  Active substance abuse&#xD;
&#xD;
          -  Less than Grade 7 education or inability to read and perform cognitive assessment.&#xD;
&#xD;
          -  Significant neurological disorder affecting memory&#xD;
&#xD;
          -  Uncontrolled atrial fibrillation prior to surgery&#xD;
&#xD;
          -  Concurrent use of prescription medications specifically for memory enhancement&#xD;
             including herbal or natural supplements&#xD;
&#xD;
          -  General anesthesia (defined as anesthesia requiring intubation or ventilatory support)&#xD;
             within 3 months prior to randomization.&#xD;
&#xD;
          -  Cardiopulmonary bypass or thoracotomy within 2 years prior to randomization.&#xD;
&#xD;
          -  Chronic obstructive pulmonary disease (COPD) requiring oxygen therapy.&#xD;
&#xD;
          -  Participants on immunosuppressive drugs, such as azathioprine, chemotherapeutic&#xD;
             agents, mycophenolate, monoclonal antibodies, or more than 20 mg/day prednisone,&#xD;
             within the previous 3 months&#xD;
&#xD;
          -  Receipt of any investigational agent or device within 30 days of screening&#xD;
&#xD;
          -  MRI contraindication not limited to abnormally high weight or height to fit in scanner&#xD;
             (Bore 70cm); Presence of device/hardware incompatible with MR imaging&#xD;
&#xD;
          -  Conditions causing severe anemia&#xD;
&#xD;
          -  Participant is practicing Jehovah Witness&#xD;
&#xD;
          -  Sexually active males not practicing a medically acceptable method of contraception,&#xD;
             unless there is documented azoospermia.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nancy K Sweitzer, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Arizona</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Banner- University Medical Center Phoenix</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Arizona Sarver Heart Center</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Suburban Hospital</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20814</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Institutes of Health</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>INOVA Heart &amp; Vascular Research</name>
      <address>
        <city>Falls Church</city>
        <state>Virginia</state>
        <zip>22042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>August 1, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 17, 2017</study_first_posted>
  <last_update_submitted>May 24, 2022</last_update_submitted>
  <last_update_submitted_qc>May 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Angiotensin I (1-7)</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/NCT03252093
org study id: HL131014
secondary id: 1U01HL131014-01A1
nct id: NCT03252093
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Coronary Artery Bypass Graft (CABG) is a surgical procedure known to be associated with
      cognitive impairment. Mechanisms of cognitive impairment are complex but may include
      insufficient oxygenation and inflammation due to exposure to the bypass circuit. Currently
      there are no approved therapeutics for the prevention or treatment of cognitive impairment in
      these patients.

      A small peptide, Angiotensin-(1-7) [Ang-(1-7)], is known to decrease inflammation in the
      brain in animal models. Early studies in humans have shown it to be safe. This peptide is
      naturally produced by the body and has anti-inflammatory and vasodilatory effects.
      Investigators believe that Ang-(1-7) may be able to help lower the risk of cognitive
      dysfunction in patients undergoing CABG.

      The goal of this project is to explore effects of the experimental peptide Angiotensin-(1-7)
      (Ang-(1-7) in patients undergoing an elective CABG surgery to determine its safety and
      efficacy to prevent cognitive dysfunction in patients undergoing CABG.
Up to 104 participants (ages 60-80) undergoing elective CABG surgery at the Banner University
      Medical Center in Tucson, AZ or at Suburban Hospital/NIH Clinical Center in Bethesda, MD,
      will be enrolled in this randomized, placebo-controlled, double-blind study of
      Angiotensin-(1-7). Subjects who have a pre-operative neurologic, learning or psychiatric
      disorder will be excluded. In addition, a concurrent group of 20 age-matched adults will be
      recruited as a neuropsychological control group and will undergo neuropsychological testing
      at baseline, Day 21 and Day 90.

      Participants will be asked to undergo a screening process to confirm eligibility and to rule
      out depression, dementia and contraindications to MRI. Prior to randomization, baseline
      measures will include neuropsychological testing, brain MRI, quality of life questionnaires,
      inflammatory markers and DNA/RNA sample collection. Participants will be treated for 21 days
      with a daily dose of subcutaneous Ang-(1-7) (100 mcg/kg/day) (n=60) or placebo (n=30). These
      measures will then be repeated at Day 21 and Day 90. The MRI will be repeated at Day 21 only.

      Pharmacokinetic measurements will be obtained prior to administration of Ang-(1-7) or placebo
      and hourly for 6 hours following the first 6 doses. Delirium testing will occur on a daily
      basis post surgery until discharge. Serum study drug level will be obtained at Day 21.

      Lastly, subjects will be followed on a weekly basis by telephone for all 12 weeks of the
      study.

        1. Primary Objective: To evaluate the safety and tolerability of 21 days of subcutaneous
           (s.c.) once daily administration of Ang-(1-7) in eligible participants undergoing
           first-time, elective coronary artery bypass graft (CABG) surgery.

        2. Secondary Objectives:

             1. To determine the pharmacokinetics of 21 days of treatment with Ang-(1-7).

             2. To determine if 21 days of treatment with 200 mcg/kg/day of Ang-(1-7) improves
                memory function measured as a change in performance from baseline to follow up on a
                composite score comprised of memory, executive functioning, language and processing
                speed in Ang-(1-7) treatment group compared to placebo controls and non-surgical
                controls.

             3. To determine if treatment with 200 mcg/kg/day Ang-(1-7) decreases postoperative
                delirium length and severity as measured with the Confusion Assessment Method (CAM)
                D2 to D7 ( or discharge) after surgery as compared to treatment with placebo group.

             4. To determine if 21 days of treatment with 200 mcg/kg/day Ang-(1-7) improves
                participant self-reported outcomes using standardized Kansas City Cardiomyopathy
                Questionnaire (KCCQ) and Instrumental Activities of Daily Living (IADL) measurement
                tools.

             5. To determine if 21 days treatment with 200 mcg/kg/day Ang-(1-7) results in changes
                in suicidal ideation and behavior as assessed by The Columbia Suicide Severity
                Rating Scale (C-SSRS).

             6. To compare postoperative mortality and morbidity at 90 days in the 200 mcg/kg/day
                Ang-(1-7) treatment group with the placebo group.

             7. To determine if 21 days of treatment of 200 mcg/kg/day Ang-(1-7) decreases
                postoperative observable changes in brain fractional anisotropy as measured by
                diffuse on magnetic resonance imaging (MRI) as compared to placebo.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Demonstrate 21 days daily administration of Ang-(1-7) in participants undergoing 1st time CABG surgery is safe and efficacious as assessed by the number of related AEs grade 3 or > and change in composite neuropsychological score up to Day 90.
time frame: Up to Day 90
description: Adverse events (AEs), including serious adverse events (SAEs) will be monitored from the time of enrollment through Day 90. The number of AEs, withdrawals due to AE, and withdrawals for other reasons will be tabulated. Additional assessments include: serum blood levels of the Ang-(1-7) at Day 1, Day 3, Day 5 or Discharge and Day 21. Lastly blood pressuring monitoring pre and post treatment will occur Day 1 to discharge.
Change in performance on composite scores of memory, executive functioning, language and processing speed in the treatment arm compared to placebo arm and non-surgical controls measured at 3 time points will assess the effectiveness of Ang-(1-7) in reducing postoperative cognitive impairment in CABG patients.
measure: Demonstrated change in the neuropsychological component scores assessed at baseline, Day 21 and Day 90 in the treatment and placebo arms.
time frame: Up to Day 90
description: The component scores to be analyzed will include Rey Auditory Verbal Learning Test (RAVLT) and Confusion Assessment Method (CAM), assessment of general intellectual functioning (North American Adult Reading Test), prospective memory (MIST; Memory Intentions Test) , Visual Paired Associates, Object-Spatial Locations, three areas of executive functions including updating (Keep Track), shifting (Letter-Number), and inhibition (Stroop Color-Word), and psychomotor speed (Deary Simple and Complex Reaction Times, Trials A and B).
measure: Evidence of change in fractional anisotropy from diffusion tensor imaging on Brain MRI at baseline versus post operative Day 21 will be assessed in the treatment and placebo arms as a measure of efficacy.
time frame: Up to Day 21
description: CABG surgery will result in observable changes in gray matter volumes and integrity of white matter as measured by structural and diffusion MR imaging in all participants. Similar voxel-based multivariate regression analyses will be used for other MRI measures including gray and white matter volumes, axial and radial diffusion, and ASL perfusion. Comparisons between CABG patients and controls will use the general linear model in SPM8 with group (CABG, controls) as a categorical factor and age as a mean-centered control variable. For structural MRI, ICV will also be included as a covariate.
measure: Demonstrated change in PBR28 VT/fP, a quantitative measure of TSPO receptor density, in a composite cerebral region-of-interest (ROI) derived from brain PET imaging in the treatment and placebo arms.
time frame: Up to Day 21
description: PBR28 VT/fP will be measured in a composite cerebral region-of-interest (ROI), including automatic anatomically labeled, bilateral medial and lateral temporal, parietal, precuneus, prefrontal ROIs (Reiman, 2009) in the treatment and placebo arms.
measure: Demonstrated associations between neuropsychogical test results, MRI findings and PBR28 binding in all participants.
time frame: Up to Day 90
description: Neuropsychological testing outcomes and MRI findings will analyzed to evaluate associations between these outcomes and PBR28 binding. In addition, systemic inflammatory markers will be measured, including GM-CSF, IFNγ, IL-1 β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, and TNFα.
arm group label: Angiotensin-(1-7)
arm group type: Experimental
description: Intervention: Drug: 200 mcg/kg/day injected subcutaneously once daily for 21 days
arm group label: Placebo for Angiotensin-(1-7)
arm group type: Placebo Comparator
description: Intervention: Placebo for Angiotensin-(1-7) injected subcutaneously once daily for 21 days
intervention type: Drug
intervention name: Angiotensin-(1-7)
description: Subcutaneous injection of 200 mcg/kg/day
arm group label: Angiotensin-(1-7)
intervention type: Drug
intervention name: Placebo for Angiotensin-(1-7)
description: Subcutaneous injection of Placebo
arm group label: Placebo for Angiotensin-(1-7)
criteria: 
gender: All
minimum age: 60 Years
maximum age: 80 Years
healthy volunteers: No
last name: Nancy K Sweitzer, MD, PhD
role: Principal Investigator
affiliation: University of Arizona
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Cognitive Dysfunction
mesh term: Angiotensin I (1-7)