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Non-Invasive Assessment of Atherosclerosis in Patients With CGD and Other Disorders of the Immune System

Completed
Conditions
Chronic Granulomatous Disease (CGD)
Atherosclerosis
Registration Number
NCT01063309
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

Background:

* Atherosclerosis, the arterial plaques or blockages that cause heart disease, develops in many people by the time they are in their mid-20s. The rate of atherosclerosis in patients with immune system disorders has not been well studied, but it may be very different from the general population.

* Patients with chronic granulomatous disease (CGD) produce less of a group of molecules known as free radicals, which help to fight infection and may play a role in the development of atherosclerosis. Patients with CGD may develop atherosclerosis much more slowly than people without CGD. On the other hand, carrier mothers of children with genetically-linked CGD often have problems with autoimmune problems in addition to a problem with making free radicals. Patients with other immune system disorders also have very different responses to infection, and many of them also have autoimmune-like problems that may change the risk of developing atherosclerosis.

Objectives:

- To study the prevalence of atherosclerosis in patients with immune system disorders, compared with healthy individuals.

Eligibility:

- Individuals at least 18 years of age who either have been diagnosed with an immune system disorder or are healthy volunteers.

Design:

* The active part of the study involves one or two visits to the National Institutes of Health Clinical Center for a series of imaging tests and scans.

* Participants will have the following tests during the active part of the study:

* (1) CAT scan to obtain images of the chest arteries and measure the amount of calcium in the artery walls.

* (2) Magnetic resonance imaging scan to obtain images of the coronary and carotid arteries in the chest and neck.

* (3) Electrocardiogram to provide data on current heart function.

* (4) Blood samples to provide data on heart, kidney, and immune system function.

* Participants will be contacted every 2 years in the future for up to 30 years to determine whether they have developed heart disease. Researchers will ask participants to provide contact information for two other people who may likely know how to get in touch with the participant in the future.

Detailed Description

Heart disease kills more than half a million people in the U.S. each year. Atherosclerosis, the major cause of heart disease, is thought to relate to dysregulated inflammation in the cardiovascular system and possibly results from over production of reactive oxygen species (ROS). The rate of atherosclerosis in patients with disorders of the immune system has not been well characterized but is likely to be dramatically different than that seen in the general population. Specifically, patients with Chronic Granulomatous Disease (CGD) may be protected from developing atherosclerosis due to reduced superoxide and other ROS production by phagocytic cells. We hypothesize that patients with CGD are at decreased risk of developing atherosclerosis. The primary objective of this study is to determine the prevalence of atherosclerosis and it s inflammatory characteristics in these and other patients with in-born disorders of immune function. The primary objective will be assessed using carotid studies and other imaging techniques to measure coronary artery calcium scores and the presence or absence of soft plaque. Secondary endpoints include physiologic characteristics such as blood pressure as well as circulating biomarkers associated with heart disease such as C-reactive protein and lipid profile. This study may lead to improved understanding of the pathophysiology of atherosclerosis, specifically the role of free radical stress, and could lead to novel therapies for atherosclerosis that may benefit patients with immune disorders and the general population.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
156
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Coronary Artery Calcium scoreSeptember 2009- December 2024

numerical value ranging from 0 to \>1000

Coronary MRI angiographySeptember 2009- December 2024

presence of absence of soft plaque

Carotid Artery Intimal Medial ThicknessSeptember 2009- December 2024

numerical value (in millimeters) representing the thickness of the artery and vessel wall volume

Coronary CT angiographySeptember 2009- December 2024

presence or absence of soft plaque

Carotid arterial FDG uptakeSeptember 2009- December 2024

target to background ratio of FDG activity measured by PET imaging.

Secondary Outcome Measures
NameTimeMethod
Cardiac MRISeptember 2009- December 2024

used to determine left ventricular wall motion and cardiac size and to determine the presence of granulomas in the ventricular wall. Results will be reported as an overall cardiac volume, left ventricular ejection fraction, the presence or absence of wall motion abnormalities, and the presence or absence of granulomas

Circulating Markers of Inflammation or Immune DysregulationSeptember 2009- December 2024

IL-8, TNF, ESR,IFN, DHR

Circulating Markers of Cardiac DiseaseSeptember 2009- December 2024

Lipid Profile, CRP,Myeloperoxidase analyzed for coronary artery disease risk.

Demographic Characteristics and Questionnaire ResultsSeptember 2009- December 2024

Standard questionnaires will be used to collect information about demographics, socioeconomic and psychosocial status, medical and family history, medication use, dietary and alcohol intakes, smoking, and physical activity. Data will be analyzed using a multivariate analysis.

Physiologic CharacteristicsSeptember 2009- December 2024

Physiologic data including blood pressure, heart rate, and pulse pressure will also be obtained. EKG will be assessed for electrocardiographic evidence of prior ischemic injury.

Trial Locations

Locations (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

🇺🇸

Bethesda, Maryland, United States

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