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PPG Project 3 - PET/MRI of the Brain-hematopoiesis-atherosclerosis Axis in PTSD Patients

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ClinicalTrials.gov Identifier: NCT03279393
Recruitment Status : Recruiting
First Posted : September 12, 2017
Last Update Posted : July 14, 2020
Sponsor:
Collaborators:
Massachusetts General Hospital
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Zahi Fayad, Icahn School of Medicine at Mount Sinai

Tracking Information
First Submitted Date  ICMJE September 8, 2017
First Posted Date  ICMJE September 12, 2017
Last Update Posted Date July 14, 2020
Actual Study Start Date  ICMJE November 28, 2017
Estimated Primary Completion Date February 28, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 8, 2017)
Atherosclerotic burden in PTSD using PET/MRI [ Time Frame: Day 1 ]
The atherosclerosis burden as measured by 18F-FDG-PET/MRI
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2017)
  • Degree of brain fear circuit activation [ Time Frame: Day 1 ]
    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.
  • Level of circulating HPSCs [ Time Frame: Day 1 ]
  • Level of circulating immune cells [ Time Frame: Day 1 ]
  • Level of soluble inflammation biomarkers [ Time Frame: Day 1 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PPG Project 3 - PET/MRI of the Brain-hematopoiesis-atherosclerosis Axis in PTSD Patients
Official Title  ICMJE Stress and Atherosclerotic Plaque Macrophages: A Systems Biology Approach - PET/MRI of the Brain-hematopoiesis-atherosclerosis Axis in PTSD Patients
Brief Summary 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.
Detailed Description

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
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • PTSD
  • Trauma
  • Healthy
Intervention  ICMJE Drug: fluorodeoxyglucose (FDG)-PET/MRI
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)
Study Arms  ICMJE
  • Active Comparator: PTSD Subjects
    Intervention: Drug: fluorodeoxyglucose (FDG)-PET/MRI
  • Active Comparator: Trauma Control Subjects
    Intervention: Drug: fluorodeoxyglucose (FDG)-PET/MRI
  • Placebo Comparator: Healthy Control Subjects
    Intervention: Drug: fluorodeoxyglucose (FDG)-PET/MRI
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 8, 2017)
240
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2022
Estimated Primary Completion Date February 28, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Inclusion criteria for Group 1 (PTSD Subjects)

  • Male or female aged 30-65 years;
  • Meets DSM-V criteria for Post-Traumatic Stress Disorder (PTSD) from at least one year prior to enrollment (as assessed using the SCID and the CAPS);
  • Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process.

Inclusion for Group 2 (Trauma Control Subjects)

  • Male or female aged 30-65 years;
  • Meets DSM-V criteria A of Post-Traumatic Stress Disorder (PTSD) from at least one year prior to enrollment, without satisfying criteria for a PTSD diagnoses according to the DSM-V (as assessed using the SCID);
  • Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process.

Inclusion criteria for Group 3 (Healthy Control Subjects)

  • Male or female aged 30-65 years;
  • Does not meet for any current or past psychiatric diagnoses as defined by DSM-V criteria;
  • Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process.

Exclusion Criteria:

  • Clinical history of atherosclerotic disease (prior myocardial infarction, stroke, peripheral artery disease)
  • Clinical history or presence of significant central nervous system and neurological diseases (e.g., TBI, multiple sclerosis)
  • History of class 3 or 4 heart failure, severe life-threatening arrhythmia (e.g., ventricular tachycardia) or severe mitral or aortic valvular disease Current, primary psychiatric disorder other than PTSD (not including ADD, ADHD)
  • History or current schizophrenia or primary psychotic disorders (e.g. schizophrenia, schizoaffective disorder)
  • Suicidal ideation with any intent or plan as measured by a Columbia Suicide Severity Rating Scale [C-SSRS] score of greater than 3 during the past month at the time of screening
  • Current or history of a major cognitive disorder or evidence of cognitive impairment as assessed by a score of the Mini Mental Status Exam (MMSE) of <24
  • Substance Use Disorder within the past 6 months;
  • Hypnotic medications used PRN are allowed except within 24 hours of the scan assessment day (V1)
  • Benzodiazepine medications used PRN (not to exceed 2 mg of lorazepam daily) are allowed except within 12 hours of the scan assessment day (V1)
  • Positive urine-toxicology (u-tox) screening for illicit substances at assessment day
  • Alcohol consumption above the NIAA cut-off for moderate alcohol intake (maximum 14 drinks for men and 7 drinks for women per week)
  • Concomitant use of high intensity statins (atorvastatin ≥ 40 mg/day; rosuvastatin > 20 mg/day; pitavastatin ≥ 2 mg/day)
  • Concomitant systemically-administered anti-inflammatory agents for chronic inflammatory conditions (e.g., methotrexate or anti-inflammatory biologics). On the other hand, NSAIDS, aspirin, and topical or inhaled steroids are permitted;
  • Chronic inflammatory conditions including but not limited to psoriasis and rheumatoid arthritis;
  • Subjects with malignancies that are within 5 years of remission are excluded.
  • Clinically significant abnormalities of laboratories or advanced systemic disease (i.e. malignancy); specific cutoffs include:
  • A value of >52 for high-sensitivity troponin (however a value between 13 and 52 will need PI clearance); a threshold of .03 and .01 respectively, for older generation troponin

    • Leukopenia: WBC <4.0
    • HsCRP >10
    • EGFR <60
    • Known or active liver disease with AST/ALT >3 times the ULN, Bil >2 times the ULN
    • Coagulation abnormalities such as INR >1.1, aPTT >34.9 (unless subject is on anticoagulation therapy)
  • Type 1 diabetes
  • Type 2 diabetes AND HbA1C > 7.5;
  • Women who are pregnant;
  • Any contraindications to MRI, including claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, and inability to lie still for 1 hour or more.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Zahi Fayad, PhD 212-824-8452 zahi.fayad@mssm.edu
Contact: Alexis Mark, MS 212-824-8458 alexis.mark@mountsinai.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03279393
Other Study ID Numbers  ICMJE GCO 15-0893 P3
1P01HL131478 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan 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.
Responsible Party Zahi Fayad, Icahn School of Medicine at Mount Sinai
Study Sponsor  ICMJE Zahi Fayad
Collaborators  ICMJE
  • Massachusetts General Hospital
  • National Heart, Lung, and Blood Institute (NHLBI)
  • National Institutes of Health (NIH)
Investigators  ICMJE
Principal Investigator: Zahi Fayad, PhD Icahn School of Medicine at Mount Sinai
PRS Account Icahn School of Medicine at Mount Sinai
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP