Clinical trial NCT01778569: The Psoriasis, Atherosclerosis, and Cardiometabolic Disease Initiative (PACI)
Official title: Human Translational Studies of Inflammation and Cardiometabolic Diseases: The Psoriasis, Atherosclerosis and Cardiometabolic Disease (PACI) Initiative
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Metabolic Disease
Cardiovascular Disease
Inflammation
Psoriasis
Keywords: Imaging
Cardiovascular Risk Factors
Inflammation
Lipoproteins
Metabolic Dysfunction
Natural History
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2013-01-29
Enrollment: 386
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Any patient with a diagnosis of chronic plaque psoriasis, psoriatic arthritis, or pustular psoriasis will be considered for this protocol.

Brief summary: Background:

- Cardiometabolic diseases are medical disorders that can occur together and affect the heart. They increase the risk of developing heart disease and diabetes. One disorder, psoriasis, is an inflammation that mostly affects the skin but can affect the entire body. Another disorder, atherosclerosis, is a process in which cholesterol is gradually deposited on the wall of arteries. This causes arteries to harden and become less flexible. Many cells that cause psoriasis also cause atherosclerosis. Researchers want to look at the relationship between cardiometabolic diseases and psoriasis.

Objectives:

- To study the relationship between psoriasis and cardiometabolic diseases.

Eligibility:

- Individuals at least 18 years of age who have psoriasis.

Design:

* Participants will be screened with a physical exam and medical history.
* Participants will have up to seven outpatient visits over the 4 years. The first visit will be a screening visit. Visits 2 will be12 months after visit 1. Visits 3, 4, and 5, will be scheduled yearly for the next 3 years. If participants have a psoriasis flare with more severe symptoms, they may have an extra visit. Those who leave the study early will have a final visit with the full series of tests.
* At visits 1, 2,and 5, and any flare visits, participants will have a physical exam and medical history. They will provide blood and urine samples, as well as optional tissue biopsies. They will also have heart function tests. Imaging studies, as well as optional photographs of affected areas, will be performed. These tests will also be performed at the final visit.
* At visits 3 and 4, participants will have a physical exam and medical history. They will also provide blood and urine samples, and have heart function tests.

Detailed description: Over the past two decades, inflammation has been identified as an important pathogenic process in cardiometabolic diseases (CMD) such atherosclerotic cardiovascular disease (CVD), dyslipidemia, insulin resistance, diabetes and obesity. However, mechanistic links between inflammation and these disease states in humans remain poorly understood. In this study, we propose to utilize psoriasis, a common, chronic inflammatory T-cell skin disease associated with increased CVD and CMD as a model to understand the effect of chronic inflammation on these diseases states. We will conduct a prospective cohort study to understand the effect of chronic inflammation on vascular and metabolic disease at the NIH Clinical Center. Furthermore, we will initiate a large scale collection of blood and skin from extramural sites to facilitate discovery of pathways involved in inflammatory modulation of CVD and CMD.

Eligibility criteria: * INCLUSION CRITERIA
* 18 years of age or older
* Diagnosed with psoriasis clinically confirmed by provider, consisting of typical skin findings and associated findings of systemic disease of joints, nails and hair)

EXCLUSION CRITERIA

* For skin and adipose biopsy, any subject with known bleeding disorder, current fever or on anticoagulation.
* Pregnant women and lactating women, may not undergo any study procedures until they are no longer pregnant or breast feeding.
* Subjects with a contraindication to MRI scanning will not receive the optional PET/MRI. These contraindications include subjects with the following devices:

  * Central nervous system aneurysm clips
  * Implanted neural stimulator
  * Implanted cardiac pacemaker or defibrillator
  * Cochlear implant
  * Ocular foreign body (e.g. metal shavings)
  * Implanted Insulin pump
  * Metal shrapnel or bullet
* Subjects with a BMI \>45 will also not receive the PET MRI.
* Subjects with severe renal excretory dysfunction, estimated glomerular filtration rate \< 30 mL/min/1.73m\^2 body surface area according to the Modification of Diet in Renal Disease criteria, will not receive the cardiac CT angiography, or gadolinium contrast agent during the PET/MRI.

Primary outcomes:
measure: Our primary outcome of interest is vascular inflammation measured by standard uptake values from PET-CT imaging with FDG.
timeFrame: 4-6 years
Secondary outcomes:
measure: Mean Aortic Wall Thickness
timeFrame: 4-6 years
measure: Coronary Artery Calcium Score
timeFrame: 4-6 years
measure: HDL function
timeFrame: 4-6 years
measure: lipoprotein particle size and number
timeFrame: 4-6 years
measure: immune, metabolic &amp; inflammation measure
timeFrame: 4-6 years
measure: Myocardial Flow Reserve (MFR)
timeFrame: 4-6 years
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Heart, Lung, and Blood Institute (NHLBI)
name: Michael N Sack, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sajja A, Abdelrahman KM, Reddy AS, Dey AK, Uceda DE, Lateef SS, Sorokin AV, Teague HL, Chung J, Rivers J, Joshi AA, Elnabawi YA, Goyal A, Rodante JA, Keel A, Alvarez JE, Lockshin B, Prussick R, Siegel E, Playford MP, Chen MY, Bluemke DA, Gelfand JM, Mehta NN. Chronic inflammation in psoriasis promotes visceral adiposity associated with noncalcified coronary burden over time. JCI Insight. 2020 Nov 19;5(22):e142534. doi: 10.1172/jci.insight.142534.
citation: Salahuddin T, Natarajan B, Playford MP, Joshi AA, Teague H, Masmoudi Y, Selwaness M, Chen MY, Bluemke DA, Mehta NN. Cholesterol efflux capacity in humans with psoriasis is inversely related to non-calcified burden of coronary atherosclerosis. Eur Heart J. 2015 Oct 14;36(39):2662-5. doi: 10.1093/eurheartj/ehv339. Epub 2015 Jul 18.
citation: Rose S, Stansky E, Dagur PK, Samsel L, Weiner E, Jahanshad A, Doveikis J, Naik HB, Playford MP, McCoy JP, Mehta NN. Characterization of immune cells in psoriatic adipose tissue. J Transl Med. 2014 Sep 16;12:258. doi: 10.1186/s12967-014-0258-2.
citation: Mehta NN, Dagur PK, Rose SM, Naik HB, Stansky E, Doveikis J, Biancotto A, Playford MP, Philip McCoy J Jr. IL-17A production in human psoriatic blood and lesions by CD146+ T cells. J Invest Dermatol. 2015 Jan;135(1):311-314. doi: 10.1038/jid.2014.317. Epub 2014 Jul 24. No abstract available.