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

NCT03279393 | Completed Early Phase 1 FDA Drug

• 2 other identifiers: GCO 15-0893 P31P01HL131478
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 2

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.

Conditions

PTSD; Trauma; Healthy

Keywords

Post-Traumatic Stress Disorder; PTSD; trauma; stress; atherosclerosis; macrophage; plaque burden; vascular inflammation; atherosclerotic inflammation; PET/MRI; 18F-FDG-PET

Outcome Measures

Primary Outcomes (1)

• Atherosclerotic burden in PTSD using PET/MRI

  The atherosclerosis burden as measured by 18F-FDG-PET/MRI

  Day 1

Secondary Outcomes (4)

• Degree of brain fear circuit activation

  Day 1

• Level of circulating HPSCs

  Day 1

• Level of circulating immune cells

  Day 1

• Level of soluble inflammation biomarkers

  Day 1

Study Arms (3)

PTSD Subjects

ACTIVE COMPARATOR

Drug: fluorodeoxyglucose (FDG)-PET/MRI

Trauma Control Subjects

ACTIVE COMPARATOR

Drug: fluorodeoxyglucose (FDG)-PET/MRI

Healthy Control Subjects

PLACEBO COMPARATOR

Drug: fluorodeoxyglucose (FDG)-PET/MRI

Interventions

fluorodeoxyglucose (FDG)-PET/MRI DRUG

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)

Healthy Control Subjects; PTSD Subjects; Trauma Control Subjects

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zahi Fayad: lead
• Massachusetts General Hospital: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (15)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Wounds and Injuries; Atherosclerosis

Interventions

Fluorodeoxyglucose F18

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Deoxyglucose; Deoxy Sugars; Carbohydrates

Study Officials

• Zahi Fayad, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Translational and Molecular Imaging Institute

Study Record Dates

• First Submitted: September 8, 2017
• First Posted: September 12, 2017
• Study Start: November 28, 2017
• Primary Completion: February 14, 2023
• Study Completion: February 14, 2023
• Last Updated: April 14, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share

Locations

US (2)