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 15, 2021
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
PTSD Trauma Healthy | Drug: fluorodeoxyglucose (FDG)-PET/MRI | Early Phase 1 |
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:
- 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.
- Blood pressure: One blood pressure reading, taken in the dominant arm, will be performed per the American Heart Association recommendations.
- 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.
- Blood draw: approximately 3 tablespoons of blood will be drawn to evaluate clinical variables.
- Imaging at Mount Sinai or Massachusetts General Hospital: A Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) scan
- Urine drug screen
- C-SSRS safety assessment
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 240 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Basic Science |
Official Title: | Stress and Atherosclerotic Plaque Macrophages: A Systems Biology Approach - PET/MRI of the Brain-hematopoiesis-atherosclerosis Axis in PTSD Patients |
Actual Study Start Date : | November 28, 2017 |
Estimated Primary Completion Date : | February 28, 2022 |
Estimated Study Completion Date : | February 28, 2022 |

Arm | Intervention/treatment |
---|---|
Active Comparator: PTSD Subjects |
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) |
Active Comparator: Trauma Control Subjects |
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) |
Placebo Comparator: Healthy Control Subjects |
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) |
- Atherosclerotic burden in PTSD using PET/MRI [ Time Frame: Day 1 ]The atherosclerosis burden as measured by 18F-FDG-PET/MRI
- 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 ]

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Ages Eligible for Study: | 30 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03279393
Contact: Mallory Stellato, MPH | (212) 824-8492 | mallory.stellato@mssm.edu | |
Contact: Alex Cardeiro, BA | 978-822-6834 | acardeiro@mgh.harvard.edu |
United States, Massachusetts | |
Massachusetts General Hospital | Recruiting |
Boston, Massachusetts, United States, 02114 | |
Contact: Ahmed Tawakol, MD atwakol@mgh.harvard.edu | |
Contact: Nikki Naddaf nnaddaf@mgh.harvard.edu | |
United States, New York | |
Icahn School of Medicine at Mount Sinai | Recruiting |
New York, New York, United States, 10029 | |
Contact: Mallory Stellato, MPH 212-824-8492 mallory.stellato@mssm.edu | |
Contact: Alex Cardeiro, BA 978-822-6834 acardeiro@mgh.harvard.edu | |
Principal Investigator: Zahi Fayad, PhD |
Principal Investigator: | Zahi Fayad, PhD | Icahn School of Medicine at Mount Sinai |
Responsible Party: | Zahi Fayad, Director of Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai |
ClinicalTrials.gov Identifier: | NCT03279393 |
Other Study ID Numbers: |
GCO 15-0893 P3 1P01HL131478 ( U.S. NIH Grant/Contract ) |
First Posted: | September 12, 2017 Key Record Dates |
Last Update Posted: | July 15, 2021 |
Last Verified: | July 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
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. |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Post-Traumatic Stress Disorder stress atherosclerosis PTSD trauma macrophage |
plaque burden vascular inflammation atherosclerotic inflammation PET/MRI 18F-FDG-PET |
Atherosclerosis Arteriosclerosis Arterial Occlusive Diseases Vascular Diseases |
Cardiovascular Diseases Fluorodeoxyglucose F18 Radiopharmaceuticals Molecular Mechanisms of Pharmacological Action |