<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/NCT03279393</url>
  </required_header>
  <id_info>
    <org_study_id>GCO 15-0893 P3</org_study_id>
    <secondary_id>1P01HL131478</secondary_id>
    <nct_id>NCT03279393</nct_id>
  </id_info>
  <brief_title>PPG Project 3 - PET/MRI of the Brain-hematopoiesis-atherosclerosis Axis in PTSD Patients</brief_title>
  <official_title>Stress and Atherosclerotic Plaque Macrophages: A Systems Biology Approach - PET/MRI of the Brain-hematopoiesis-atherosclerosis Axis in PTSD Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zahi Fayad</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Icahn School of Medicine at Mount Sinai</source>
  <oversight_info>
    <has_dmc>No</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>
      Project 3 of the PPG grant &quot;Stress and Atherosclerotic Plaque Macrophages A Systems Biology&#xD;
      Approach,&quot; funded by the NHLBI, examines the relationship between psychosocial stress and&#xD;
      atherosclerotic inflammation, cell proliferation and burden using novel PET/MRI. Individuals&#xD;
      with post-traumatic stress disorder, trauma controls and healthy controls will be recruited&#xD;
      into a two-center clinical study. The study team will use functional MRI to examine the&#xD;
      relationship between activation of fear circuits in the brain and relate these data to&#xD;
      hematopoietic system activation, and vascular inflammation measured by FDG-PET, and&#xD;
      atherosclerotic burden measured by MRI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In Project 3, the study team will employ innovative PET combined with magnetic resonance&#xD;
      imaging (PET/MRI) to simultaneously study the hematopoietic system, the artery wall, and the&#xD;
      brain's fear system, which comprises the amygdala and anterior cingulate cortex (ACC), to&#xD;
      elucidate the relationship between psychosocial stress and systemic&#xD;
      inflammation/atherosclerosis in a two center clinical study looking at: I) individuals with&#xD;
      PTSD, II) individuals without PTSD but with exposure to severe psychosocial trauma (Trauma&#xD;
      Control), and III) matched volunteers with neither PTSD nor exposure to trauma (Healthy&#xD;
      Control). Participants in the three study groups, recruited from urban settings in New York&#xD;
      and Boston, will be group-matched by age, gender, and Framingham risk scores (FRS). The study&#xD;
      team will recruit 80 subjects in each group and in Aim 1, investigate the relationship&#xD;
      between PTSD and atherosclerotic inflammation and burden measured by PET/MRI. In Aim 2, the&#xD;
      study team will examine the relationships between brain's fear circuit responsiveness to&#xD;
      threat assessed by functional MRI (fMRI) and white matter integrity assessed by diffusion&#xD;
      tensor imaging (DTI) and relate these data to hematopoietic system activation, and vascular&#xD;
      inflammation measured by fluorodeoxyglucose (FDG)-PET and atherosclerotic burden measured by&#xD;
      MRI.&#xD;
&#xD;
      The following will occur during the imaging visit:&#xD;
&#xD;
        1. Questionnaire: study staff will administer a standardized questionnaire to collect&#xD;
           general information on age, gender, race, and current contact information. A PET/MRI&#xD;
           pre-screening form will also be administered to confirm eligibility for the PET/MRI&#xD;
           scan. This questionnaire is specific to the PET/MRI scan.&#xD;
&#xD;
        2. Blood pressure: One blood pressure reading, taken in the dominant arm, will be performed&#xD;
           per the American Heart Association recommendations.&#xD;
&#xD;
        3. Anthropometrics: Body weight and height will be measured according to standard methods&#xD;
           and body mass index will be calculated as an index for obesity. Waist circumference will&#xD;
           also be measured.&#xD;
&#xD;
        4. Blood draw: approximately 3 tablespoons of blood will be drawn to evaluate clinical&#xD;
           variables.&#xD;
&#xD;
        5. Imaging at Mount Sinai or Massachusetts General Hospital: A Positron Emission&#xD;
           Tomography/Magnetic Resonance Imaging (PET/MRI) scan&#xD;
&#xD;
        6. Urine drug screen&#xD;
&#xD;
        7. C-SSRS safety assessment&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 28, 2017</start_date>
  <completion_date type="Actual">February 14, 2023</completion_date>
  <primary_completion_date type="Actual">February 14, 2023</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Atherosclerotic burden in PTSD using PET/MRI</measure>
    <time_frame>Day 1</time_frame>
    <description>The atherosclerosis burden as measured by 18F-FDG-PET/MRI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Degree of brain fear circuit activation</measure>
    <time_frame>Day 1</time_frame>
    <description>The degree of brain fear circuit activation (both at rest and in response to validated stimuli) to be associated with activation of hematopoietic organs 18F-FDG PET imaging.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of circulating HPSCs</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of circulating immune cells</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of soluble inflammation biomarkers</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">190</enrollment>
  <condition>PTSD</condition>
  <condition>Trauma</condition>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>PTSD Subjects</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Trauma Control Subjects</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Control Subjects</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>fluorodeoxyglucose (FDG)-PET/MRI</intervention_name>
    <description>Innovative PET combined with magnetic resonance imaging (PET/MRI) to simultaneously study the hematopoietic system, the artery wall, and the brain's fear system, which comprises the amygdala and anterior cingulate cortex (ACC)</description>
    <arm_group_label>Healthy Control Subjects</arm_group_label>
    <arm_group_label>PTSD Subjects</arm_group_label>
    <arm_group_label>Trauma Control Subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Inclusion criteria for Group 1 (PTSD Subjects)&#xD;
&#xD;
          -  Male or female aged 30-65 years;&#xD;
&#xD;
          -  Meets DSM-V criteria for Post-Traumatic Stress Disorder (PTSD) from at least one year&#xD;
             prior to enrollment (as assessed using the SCID and the CAPS);&#xD;
&#xD;
          -  Participants must have a level of understanding of the English language sufficient to&#xD;
             agree to all tests and examinations required by the study and must be able to&#xD;
             participate fully in the informed consent process.&#xD;
&#xD;
        Inclusion for Group 2 (Trauma Control Subjects)&#xD;
&#xD;
          -  Male or female aged 30-65 years;&#xD;
&#xD;
          -  Meets DSM-V criteria A of Post-Traumatic Stress Disorder (PTSD) from at least one year&#xD;
             prior to enrollment, without satisfying criteria for a PTSD diagnoses according to the&#xD;
             DSM-V (as assessed using the SCID);&#xD;
&#xD;
          -  Participants must have a level of understanding of the English language sufficient to&#xD;
             agree to all tests and examinations required by the study and must be able to&#xD;
             participate fully in the informed consent process.&#xD;
&#xD;
        Inclusion criteria for Group 3 (Healthy Control Subjects)&#xD;
&#xD;
          -  Male or female aged 30-65 years;&#xD;
&#xD;
          -  Does not meet for any current or past psychiatric diagnoses as defined by DSM-V&#xD;
             criteria;&#xD;
&#xD;
          -  Participants must have a level of understanding of the English language sufficient to&#xD;
             agree to all tests and examinations required by the study and must be able to&#xD;
             participate fully in the informed consent process.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinical history of atherosclerotic disease (prior myocardial infarction, stroke,&#xD;
             peripheral artery disease)&#xD;
&#xD;
          -  Clinical history or presence of significant central nervous system and neurological&#xD;
             diseases (e.g., TBI, multiple sclerosis)&#xD;
&#xD;
          -  History of class 3 or 4 heart failure, severe life-threatening arrhythmia (e.g.,&#xD;
             ventricular tachycardia) or severe mitral or aortic valvular disease Current, primary&#xD;
             psychiatric disorder other than PTSD (not including ADD, ADHD)&#xD;
&#xD;
          -  History or current schizophrenia or primary psychotic disorders (e.g. schizophrenia,&#xD;
             schizoaffective disorder)&#xD;
&#xD;
          -  Suicidal ideation with any intent or plan as measured by a Columbia Suicide Severity&#xD;
             Rating Scale [C-SSRS] score of greater than 3 during the past month at the time of&#xD;
             screening&#xD;
&#xD;
          -  Current or history of a major cognitive disorder or evidence of cognitive impairment&#xD;
             as assessed by a score of the Mini Mental Status Exam (MMSE) of &lt;24&#xD;
&#xD;
          -  Substance Use Disorder within the past 6 months;&#xD;
&#xD;
          -  Hypnotic medications used PRN are allowed except within 24 hours of the scan&#xD;
             assessment day (V1)&#xD;
&#xD;
          -  Benzodiazepine medications used PRN (not to exceed 2 mg of lorazepam daily) are&#xD;
             allowed except within 12 hours of the scan assessment day (V1)&#xD;
&#xD;
          -  Positive urine-toxicology (u-tox) screening for illicit substances at assessment day&#xD;
&#xD;
          -  Alcohol consumption above the NIAA cut-off for moderate alcohol intake (maximum 14&#xD;
             drinks for men and 7 drinks for women per week)&#xD;
&#xD;
          -  Concomitant use of high intensity statins (atorvastatin ≥ 40 mg/day; rosuvastatin &gt; 20&#xD;
             mg/day; pitavastatin ≥ 2 mg/day)&#xD;
&#xD;
          -  Concomitant systemically-administered anti-inflammatory agents for chronic&#xD;
             inflammatory conditions (e.g., methotrexate or anti-inflammatory biologics). On the&#xD;
             other hand, NSAIDS, aspirin, and topical or inhaled steroids are permitted;&#xD;
&#xD;
          -  Chronic inflammatory conditions including but not limited to psoriasis and rheumatoid&#xD;
             arthritis;&#xD;
&#xD;
          -  Subjects with malignancies that are within 5 years of remission are excluded.&#xD;
&#xD;
          -  Clinically significant abnormalities of laboratories or advanced systemic disease&#xD;
             (i.e. malignancy); specific cutoffs include:&#xD;
&#xD;
          -  A value of &gt;52 for high-sensitivity troponin (however a value between 13 and 52 will&#xD;
             need PI clearance); a threshold of .03 and .01 respectively, for older generation&#xD;
             troponin&#xD;
&#xD;
               -  Leukopenia: WBC &lt;4.0&#xD;
&#xD;
               -  HsCRP &gt;10&#xD;
&#xD;
               -  EGFR &lt;60&#xD;
&#xD;
               -  Known or active liver disease with AST/ALT &gt;3 times the ULN, Bil &gt;2 times the ULN&#xD;
&#xD;
               -  Coagulation abnormalities such as INR &gt;1.1, aPTT &gt;34.9 (unless subject is on&#xD;
                  anticoagulation therapy)&#xD;
&#xD;
          -  Type 1 diabetes&#xD;
&#xD;
          -  Type 2 diabetes AND HbA1C &gt; 7.5;&#xD;
&#xD;
          -  Women who are pregnant;&#xD;
&#xD;
          -  Any contraindications to MRI, including claustrophobia, any trauma or surgery which&#xD;
             may have left magnetic material in the body, magnetic implants or pacemakers, and&#xD;
             inability to lie still for 1 hour or more.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zahi Fayad, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Icahn School of Medicine at Mount Sinai</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Fuster V, Kovacic JC. Acute coronary syndromes: pathology, diagnosis, genetics, prevention, and treatment. Circ Res. 2014 Jun 6;114(12):1847-51. doi: 10.1161/CIRCRESAHA.114.302806. Epub 2014 May 13. No abstract available.</citation>
    <PMID>24824094</PMID>
  </reference>
  <reference>
    <citation>Fuster V, Stein B, Ambrose JA, Badimon L, Badimon JJ, Chesebro JH. Atherosclerotic plaque rupture and thrombosis. Evolving concepts. Circulation. 1990 Sep;82(3 Suppl):II47-59.</citation>
    <PMID>2203564</PMID>
  </reference>
  <reference>
    <citation>Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol. 2006 Jul;6(7):508-19. doi: 10.1038/nri1882. Epub 2006 Jun 16.</citation>
    <PMID>16778830</PMID>
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  <reference>
    <citation>Heidt T, Sager HB, Courties G, Dutta P, Iwamoto Y, Zaltsman A, von Zur Muhlen C, Bode C, Fricchione GL, Denninger J, Lin CP, Vinegoni C, Libby P, Swirski FK, Weissleder R, Nahrendorf M. Chronic variable stress activates hematopoietic stem cells. Nat Med. 2014 Jul;20(7):754-758. doi: 10.1038/nm.3589. Epub 2014 Jun 22.</citation>
    <PMID>24952646</PMID>
  </reference>
  <reference>
    <citation>Brudey C, Park J, Wiaderkiewicz J, Kobayashi I, Mellman TA, Marvar PJ. Autonomic and inflammatory consequences of posttraumatic stress disorder and the link to cardiovascular disease. Am J Physiol Regul Integr Comp Physiol. 2015 Aug 15;309(4):R315-21. doi: 10.1152/ajpregu.00343.2014. Epub 2015 Jun 10.</citation>
    <PMID>26062635</PMID>
  </reference>
  <reference>
    <citation>Plantinga L, Bremner JD, Miller AH, Jones DP, Veledar E, Goldberg J, Vaccarino V. Association between posttraumatic stress disorder and inflammation: a twin study. Brain Behav Immun. 2013 May;30:125-32. doi: 10.1016/j.bbi.2013.01.081. Epub 2013 Feb 4.</citation>
    <PMID>23379997</PMID>
  </reference>
  <reference>
    <citation>Nahrendorf M, Swirski FK. Lifestyle effects on hematopoiesis and atherosclerosis. Circ Res. 2015 Feb 27;116(5):884-94. doi: 10.1161/CIRCRESAHA.116.303550.</citation>
    <PMID>25722442</PMID>
  </reference>
  <reference>
    <citation>Edmondson D, Kronish IM, Shaffer JA, Falzon L, Burg MM. Posttraumatic stress disorder and risk for coronary heart disease: a meta-analytic review. Am Heart J. 2013 Nov;166(5):806-14. doi: 10.1016/j.ahj.2013.07.031. Epub 2013 Sep 24.</citation>
    <PMID>24176435</PMID>
  </reference>
  <reference>
    <citation>Thakur GS, Daigle BJ Jr, Dean KR, Zhang Y, Rodriguez-Fernandez M, Hammamieh R, Yang R, Jett M, Palma J, Petzold LR, Doyle FJ 3rd. Systems biology approach to understanding post-traumatic stress disorder. Mol Biosyst. 2015 Apr;11(4):980-93. doi: 10.1039/c4mb00404c.</citation>
    <PMID>25627823</PMID>
  </reference>
  <reference>
    <citation>Graebe M, Borgwardt L, Hojgaard L, Sillesen H, Kjaer A. When to image carotid plaque inflammation with FDG PET/CT. Nucl Med Commun. 2010 Sep;31(9):773-9. doi: 10.1097/MNM.0b013e32833c365e.</citation>
    <PMID>20543757</PMID>
  </reference>
  <reference>
    <citation>Tawakol A, Fayad ZA, Mogg R, Alon A, Klimas MT, Dansky H, Subramanian SS, Abdelbaky A, Rudd JH, Farkouh ME, Nunes IO, Beals CR, Shankar SS. Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a multicenter fluorodeoxyglucose-positron emission tomography/computed tomography feasibility study. J Am Coll Cardiol. 2013 Sep 3;62(10):909-17. doi: 10.1016/j.jacc.2013.04.066. Epub 2013 May 30.</citation>
    <PMID>23727083</PMID>
  </reference>
  <reference>
    <citation>Calcagno C, Cornily JC, Hyafil F, Rudd JH, Briley-Saebo KC, Mani V, Goldschlager G, Machac J, Fuster V, Fayad ZA. Detection of neovessels in atherosclerotic plaques of rabbits using dynamic contrast enhanced MRI and 18F-FDG PET. Arterioscler Thromb Vasc Biol. 2008 Jul;28(7):1311-7. doi: 10.1161/ATVBAHA.108.166173. Epub 2008 May 8.</citation>
    <PMID>18467641</PMID>
  </reference>
  <reference>
    <citation>Hodes GE, Pfau ML, Leboeuf M, Golden SA, Christoffel DJ, Bregman D, Rebusi N, Heshmati M, Aleyasin H, Warren BL, Lebonte B, Horn S, Lapidus KA, Stelzhammer V, Wong EH, Bahn S, Krishnan V, Bolanos-Guzman CA, Murrough JW, Merad M, Russo SJ. Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress. Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):16136-41. doi: 10.1073/pnas.1415191111. Epub 2014 Oct 20.</citation>
    <PMID>25331895</PMID>
  </reference>
  <reference>
    <citation>Kim EJ, Kim S, Kang DO, Seo HS. Metabolic activity of the spleen and bone marrow in patients with acute myocardial infarction evaluated by 18f-fluorodeoxyglucose positron emission tomograpic imaging. Circ Cardiovasc Imaging. 2014 May;7(3):454-60. doi: 10.1161/CIRCIMAGING.113.001093. Epub 2014 Jan 31.</citation>
    <PMID>24488982</PMID>
  </reference>
  <reference>
    <citation>Shin LM, Lasko NB, Macklin ML, Karpf RD, Milad MR, Orr SP, Goetz JM, Fischman AJ, Rauch SL, Pitman RK. Resting metabolic activity in the cingulate cortex and vulnerability to posttraumatic stress disorder. Arch Gen Psychiatry. 2009 Oct;66(10):1099-107. doi: 10.1001/archgenpsychiatry.2009.138.</citation>
    <PMID>19805700</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>September 8, 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>April 13, 2023</last_update_submitted>
  <last_update_submitted_qc>April 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Icahn School of Medicine at Mount Sinai</investigator_affiliation>
    <investigator_full_name>Zahi Fayad</investigator_full_name>
    <investigator_title>Director of Translational and Molecular Imaging Institute</investigator_title>
  </responsible_party>
  <keyword>Post-Traumatic Stress Disorder</keyword>
  <keyword>PTSD</keyword>
  <keyword>trauma</keyword>
  <keyword>stress</keyword>
  <keyword>atherosclerosis</keyword>
  <keyword>macrophage</keyword>
  <keyword>plaque burden</keyword>
  <keyword>vascular inflammation</keyword>
  <keyword>atherosclerotic inflammation</keyword>
  <keyword>PET/MRI</keyword>
  <keyword>18F-FDG-PET</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atherosclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluorodeoxyglucose F18</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>After each imaging visit, de-identified images of the subject will be transferred via a secure BrickFTP server to the Coordinating Center (Icahn School of Medicine at Mount Sinai) for storage and analysis.</ipd_description>
  </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/NCT03279393
org study id: GCO 15-0893 P3
secondary id: 1P01HL131478
nct id: NCT03279393
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Project 3 of the PPG grant "Stress and Atherosclerotic Plaque Macrophages A Systems Biology
      Approach," funded by the NHLBI, examines the relationship between psychosocial stress and
      atherosclerotic inflammation, cell proliferation and burden using novel PET/MRI. Individuals
      with post-traumatic stress disorder, trauma controls and healthy controls will be recruited
      into a two-center clinical study. The study team will use functional MRI to examine the
      relationship between activation of fear circuits in the brain and relate these data to
      hematopoietic system activation, and vascular inflammation measured by FDG-PET, and
      atherosclerotic burden measured by MRI.
In Project 3, the study team will employ innovative PET combined with magnetic resonance
      imaging (PET/MRI) to simultaneously study the hematopoietic system, the artery wall, and the
      brain's fear system, which comprises the amygdala and anterior cingulate cortex (ACC), to
      elucidate the relationship between psychosocial stress and systemic
      inflammation/atherosclerosis in a two center clinical study looking at: I) individuals with
      PTSD, II) individuals without PTSD but with exposure to severe psychosocial trauma (Trauma
      Control), and III) matched volunteers with neither PTSD nor exposure to trauma (Healthy
      Control). Participants in the three study groups, recruited from urban settings in New York
      and Boston, will be group-matched by age, gender, and Framingham risk scores (FRS). The study
      team will recruit 80 subjects in each group and in Aim 1, investigate the relationship
      between PTSD and atherosclerotic inflammation and burden measured by PET/MRI. In Aim 2, the
      study team will examine the relationships between brain's fear circuit responsiveness to
      threat assessed by functional MRI (fMRI) and white matter integrity assessed by diffusion
      tensor imaging (DTI) and relate these data to hematopoietic system activation, and vascular
      inflammation measured by fluorodeoxyglucose (FDG)-PET and atherosclerotic burden measured by
      MRI.

      The following will occur during the imaging visit:

        1. Questionnaire: study staff will administer a standardized questionnaire to collect
           general information on age, gender, race, and current contact information. A PET/MRI
           pre-screening form will also be administered to confirm eligibility for the PET/MRI
           scan. This questionnaire is specific to the PET/MRI scan.

        2. Blood pressure: One blood pressure reading, taken in the dominant arm, will be performed
           per the American Heart Association recommendations.

        3. Anthropometrics: Body weight and height will be measured according to standard methods
           and body mass index will be calculated as an index for obesity. Waist circumference will
           also be measured.

        4. Blood draw: approximately 3 tablespoons of blood will be drawn to evaluate clinical
           variables.

        5. Imaging at Mount Sinai or Massachusetts General Hospital: A Positron Emission
           Tomography/Magnetic Resonance Imaging (PET/MRI) scan

        6. Urine drug screen

        7. C-SSRS safety assessment
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Atherosclerotic burden in PTSD using PET/MRI
time frame: Day 1
description: The atherosclerosis burden as measured by 18F-FDG-PET/MRI
measure: Degree of brain fear circuit activation
time frame: Day 1
description: The degree of brain fear circuit activation (both at rest and in response to validated stimuli) to be associated with activation of hematopoietic organs 18F-FDG PET imaging.
measure: Level of circulating HPSCs
time frame: Day 1
measure: Level of circulating immune cells
time frame: Day 1
measure: Level of soluble inflammation biomarkers
time frame: Day 1
arm group label: PTSD Subjects
arm group type: Active Comparator
arm group label: Trauma Control Subjects
arm group type: Active Comparator
arm group label: Healthy Control Subjects
arm group type: Placebo Comparator
intervention type: Drug
intervention name: fluorodeoxyglucose (FDG)-PET/MRI
description: Innovative PET combined with magnetic resonance imaging (PET/MRI) to simultaneously study the hematopoietic system, the artery wall, and the brain's fear system, which comprises the amygdala and anterior cingulate cortex (ACC)
arm group label: Healthy Control Subjects
arm group label: PTSD Subjects
arm group label: Trauma Control Subjects
criteria: 
gender: All
minimum age: 30 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Zahi Fayad, PhD
role: Principal Investigator
affiliation: Icahn School of Medicine at Mount Sinai
facility: 
facility: 
country: United States
citation: Fuster V, Kovacic JC. Acute coronary syndromes: pathology, diagnosis, genetics, prevention, and treatment. Circ Res. 2014 Jun 6;114(12):1847-51. doi: 10.1161/CIRCRESAHA.114.302806. Epub 2014 May 13. No abstract available.
PMID: 24824094
citation: Fuster V, Stein B, Ambrose JA, Badimon L, Badimon JJ, Chesebro JH. Atherosclerotic plaque rupture and thrombosis. Evolving concepts. Circulation. 1990 Sep;82(3 Suppl):II47-59.
PMID: 2203564
citation: Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol. 2006 Jul;6(7):508-19. doi: 10.1038/nri1882. Epub 2006 Jun 16.
PMID: 16778830
citation: Heidt T, Sager HB, Courties G, Dutta P, Iwamoto Y, Zaltsman A, von Zur Muhlen C, Bode C, Fricchione GL, Denninger J, Lin CP, Vinegoni C, Libby P, Swirski FK, Weissleder R, Nahrendorf M. Chronic variable stress activates hematopoietic stem cells. Nat Med. 2014 Jul;20(7):754-758. doi: 10.1038/nm.3589. Epub 2014 Jun 22.
PMID: 24952646
citation: Brudey C, Park J, Wiaderkiewicz J, Kobayashi I, Mellman TA, Marvar PJ. Autonomic and inflammatory consequences of posttraumatic stress disorder and the link to cardiovascular disease. Am J Physiol Regul Integr Comp Physiol. 2015 Aug 15;309(4):R315-21. doi: 10.1152/ajpregu.00343.2014. Epub 2015 Jun 10.
PMID: 26062635
citation: Plantinga L, Bremner JD, Miller AH, Jones DP, Veledar E, Goldberg J, Vaccarino V. Association between posttraumatic stress disorder and inflammation: a twin study. Brain Behav Immun. 2013 May;30:125-32. doi: 10.1016/j.bbi.2013.01.081. Epub 2013 Feb 4.
PMID: 23379997
citation: Nahrendorf M, Swirski FK. Lifestyle effects on hematopoiesis and atherosclerosis. Circ Res. 2015 Feb 27;116(5):884-94. doi: 10.1161/CIRCRESAHA.116.303550.
PMID: 25722442
citation: Edmondson D, Kronish IM, Shaffer JA, Falzon L, Burg MM. Posttraumatic stress disorder and risk for coronary heart disease: a meta-analytic review. Am Heart J. 2013 Nov;166(5):806-14. doi: 10.1016/j.ahj.2013.07.031. Epub 2013 Sep 24.
PMID: 24176435
citation: Thakur GS, Daigle BJ Jr, Dean KR, Zhang Y, Rodriguez-Fernandez M, Hammamieh R, Yang R, Jett M, Palma J, Petzold LR, Doyle FJ 3rd. Systems biology approach to understanding post-traumatic stress disorder. Mol Biosyst. 2015 Apr;11(4):980-93. doi: 10.1039/c4mb00404c.
PMID: 25627823
citation: Graebe M, Borgwardt L, Hojgaard L, Sillesen H, Kjaer A. When to image carotid plaque inflammation with FDG PET/CT. Nucl Med Commun. 2010 Sep;31(9):773-9. doi: 10.1097/MNM.0b013e32833c365e.
PMID: 20543757
citation: Tawakol A, Fayad ZA, Mogg R, Alon A, Klimas MT, Dansky H, Subramanian SS, Abdelbaky A, Rudd JH, Farkouh ME, Nunes IO, Beals CR, Shankar SS. Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a multicenter fluorodeoxyglucose-positron emission tomography/computed tomography feasibility study. J Am Coll Cardiol. 2013 Sep 3;62(10):909-17. doi: 10.1016/j.jacc.2013.04.066. Epub 2013 May 30.
PMID: 23727083
citation: Calcagno C, Cornily JC, Hyafil F, Rudd JH, Briley-Saebo KC, Mani V, Goldschlager G, Machac J, Fuster V, Fayad ZA. Detection of neovessels in atherosclerotic plaques of rabbits using dynamic contrast enhanced MRI and 18F-FDG PET. Arterioscler Thromb Vasc Biol. 2008 Jul;28(7):1311-7. doi: 10.1161/ATVBAHA.108.166173. Epub 2008 May 8.
PMID: 18467641
citation: Hodes GE, Pfau ML, Leboeuf M, Golden SA, Christoffel DJ, Bregman D, Rebusi N, Heshmati M, Aleyasin H, Warren BL, Lebonte B, Horn S, Lapidus KA, Stelzhammer V, Wong EH, Bahn S, Krishnan V, Bolanos-Guzman CA, Murrough JW, Merad M, Russo SJ. Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress. Proc Natl Acad Sci U S A. 2014 Nov 11;111(45):16136-41. doi: 10.1073/pnas.1415191111. Epub 2014 Oct 20.
PMID: 25331895
citation: Kim EJ, Kim S, Kang DO, Seo HS. Metabolic activity of the spleen and bone marrow in patients with acute myocardial infarction evaluated by 18f-fluorodeoxyglucose positron emission tomograpic imaging. Circ Cardiovasc Imaging. 2014 May;7(3):454-60. doi: 10.1161/CIRCIMAGING.113.001093. Epub 2014 Jan 31.
PMID: 24488982
citation: Shin LM, Lasko NB, Macklin ML, Karpf RD, Milad MR, Orr SP, Goetz JM, Fischman AJ, Rauch SL, Pitman RK. Resting metabolic activity in the cingulate cortex and vulnerability to posttraumatic stress disorder. Arch Gen Psychiatry. 2009 Oct;66(10):1099-107. doi: 10.1001/archgenpsychiatry.2009.138.
PMID: 19805700
responsible party type: Sponsor-Investigator
investigator affiliation: Icahn School of Medicine at Mount Sinai
investigator full name: Zahi Fayad
investigator title: Director of Translational and Molecular Imaging Institute
mesh term: Atherosclerosis
mesh term: Fluorodeoxyglucose F18
sharing ipd: Yes
ipd description: After each imaging visit, de-identified images of the subject will be transferred via a secure BrickFTP server to the Coordinating Center (Icahn School of Medicine at Mount Sinai) for storage and analysis.