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

NCT01063309 | Completed

• 2 other identifiers: 10002910-I-0029
• Study Type: observational
• Target: 156
• Locations: 1 country
• Sites: 1

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.

Conditions

Atherosclerosis; Chronic Granulomatous Disease (CGD)

Keywords

CAT SCAN; Heart Disease; Magnetic Resonance Imaging; Electrocardiogram; Superoxide

Outcome Measures

Primary Outcomes (5)

• Coronary CT angiography

  presence or absence of soft plaque

  September 2009- December 2024

• Coronary Artery Calcium score

  numerical value ranging from 0 to \>1000

  September 2009- December 2024

• Coronary MRI angiography

  presence of absence of soft plaque

  September 2009- December 2024

• Carotid Artery Intimal Medial Thickness

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

  September 2009- December 2024

• Carotid arterial FDG uptake

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

  September 2009- December 2024

Secondary Outcomes (5)

• Circulating Markers of Cardiac Disease

  September 2009- December 2024

• Demographic Characteristics and Questionnaire Results

  September 2009- December 2024

• Physiologic Characteristics

  September 2009- December 2024

• Circulating Markers of Inflammation or Immune Dysregulation

  September 2009- December 2024

• Cardiac MRI

  September 2009- December 2024

Study Arms (7)

Autosomal recessive CGD

Participants must have autosomal recessive CGD (p47phox, p67phox, or p22phox deficiency) as demonstrated by DHR or genetic screening.

CGD carrier

Participants with confirmed as X-linked CGD carriers as demonstrated by DHR or genetic screening.

Healthy Volunteer

Healthy volunteers over the age of 18, both male and female. That have not been diagnosed with CGD, Inflammatory Bowel Disease, or another primary disease of the immune system.

IFN-gamma treated CGD

Participants with CGD the have been treated with Interferon gamma.

Inflammatory bowel disease

Participants with Inflammatory Bowel Disease with a well-recognized granulomatous inflammation, but normal phagocyte function and ROS production. They have not been diagnosed with CGD.

Other immune system disorders

Participants with other disorders such as Chediak-Higashi Syndrome, Leukocyte Adhesion Deficiency, myeloperoxidase deficiency, Hyper- IgE (Job's) Syndrome, IRAK4-deficiency, and NEMO-deficiency

X-linked Chronic Granulomatous Disease (CGD)

Participants diagnosed with X-linked CGD confirmed by DHR.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients will be identified for this protocol who are enrolled on existing protocols studying patients with disorders of the immune system who volunteer for participation and who do not have any of the listed exclusion criteria. Normal volunteers will be enrolled as controls on this protocol. They will be recruited through the normal volunteer office, which will provide a list of volunteers including their age to allow for inclusion of controls that approximate the study population.All participants enrolled on this protocol will be over the age of 18 and may be male or female and will be accrued without regard to religion, race or sexual orientation.

You may not qualify if:

• All patients enrolled on this protocol will be over the age of 18 and may be male or female and will be accrued without regard to religion, race or sexual orientation. They must be able to understand and sign informed consent documents and comply with study procedures that include undergoing a CT scan and an MRI scan. Patients who are unable or unwilling to complete one or more of the studies will not be excluded. The available data will be included in the appropriate analysis.
• For Participation in MRI-Based Studies Only:
• Subjects with contraindication to MRI scanning. These contraindications include but are not limited to the following devices or conditions:
• Implanted cardiac pacemaker or defibrillator
• Cochlear Implants
• Ocular foreign body (i.e., metal shavings)
• Embedded shrapnel fragments
• Central nervous system aneurysm clips
• Implanted neural stimulator
• Medical infusion pumps
• Any implanted device that is incompatible with MRI
• Patients whose medical condition is such that in the referring physicians estimation, they could not tolerate an MRI scan. Examples of medical conditions that would not be accepted would include unstable angina and dyspnea at rest.
• Subjects with a condition precluding entry into the scanner (e.g. morbid obesity, claustrophobia, etc.) or who require more than oral sedation (i.e. IV sedation) for anxiety associate with MRI studies.
• Pregnant or lactating women are excluded from this study because excessive exposure of the developing human fetus and child to radiation and/or intravenous contrast agents can be detrimental.
• Subjects with severe back-pain or motion disorders who will be unable to tolerate supine positioning within the MRI scanner and hold still for the duration of the examination.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Winkelstein JA, Marino MC, Johnston RB Jr, Boyle J, Curnutte J, Gallin JI, Malech HL, Holland SM, Ochs H, Quie P, Buckley RH, Foster CB, Chanock SJ, Dickler H. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore). 2000 May;79(3):155-69. doi: 10.1097/00005792-200005000-00003.

  PMID: 10844935 BACKGROUND

• Lassegue B, Sorescu D, Szocs K, Yin Q, Akers M, Zhang Y, Grant SL, Lambeth JD, Griendling KK. Novel gp91(phox) homologues in vascular smooth muscle cells : nox1 mediates angiotensin II-induced superoxide formation and redox-sensitive signaling pathways. Circ Res. 2001 May 11;88(9):888-94. doi: 10.1161/hh0901.090299.

  PMID: 11348997 BACKGROUND

• Sorescu D, Weiss D, Lassegue B, Clempus RE, Szocs K, Sorescu GP, Valppu L, Quinn MT, Lambeth JD, Vega JD, Taylor WR, Griendling KK. Superoxide production and expression of nox family proteins in human atherosclerosis. Circulation. 2002 Mar 26;105(12):1429-35. doi: 10.1161/01.cir.0000012917.74432.66.

  PMID: 11914250 BACKGROUND

• Sibley CT, Estwick T, Zavodni A, Huang CY, Kwan AC, Soule BP, Long Priel DA, Remaley AT, Rudman Spergel AK, Turkbey EB, Kuhns DB, Holland SM, Malech HL, Zarember KA, Bluemke DA, Gallin JI. Assessment of atherosclerosis in chronic granulomatous disease. Circulation. 2014 Dec 2;130(23):2031-9. doi: 10.1161/CIRCULATIONAHA.113.006824. Epub 2014 Sep 19.

  PMID: 25239440 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Atherosclerosis; Granulomatous Disease, Chronic; Heart Diseases

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Phagocyte Bactericidal Dysfunction; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• John I Gallin, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2010
• First Posted: February 5, 2010
• Study Start: January 5, 2010
• Primary Completion: December 31, 2018
• Study Completion: August 26, 2020
• Last Updated: July 28, 2021

Record last verified: 2021-07

Locations

US (1)