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

April 13, 2023 updated by: Zahi Fayad

Stress and Atherosclerotic Plaque Macrophages: A Systems Biology Approach - PET/MRI of the Brain-hematopoiesis-atherosclerosis Axis in PTSD Patients

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
190

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • New York
      • New York, New York, United States, 10029
        • ICAHN School of Medicine at Mount Sinai

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

30 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Atherosclerotic burden in PTSD using PET/MRI
Time Frame: Day 1
The atherosclerosis burden as measured by 18F-FDG-PET/MRI
Day 1

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Day 1
Level of circulating HPSCs
Time Frame: Day 1
Day 1
Level of circulating immune cells
Time Frame: Day 1
Day 1
Level of soluble inflammation biomarkers
Time Frame: Day 1
Day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Zahi Fayad

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Massachusetts General Hospital
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Zahi Fayad, PhD, ICAHN School of Medicine at Mount Sinai

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 28, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 14, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 14, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 8, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 8, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 12, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 14, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 13, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GCO 15-0893 P3
  • 1P01HL131478 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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