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Human Atherosclerotic Plaque Inflammation Imaged Using PDG-PET/CT

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kevin Yarasheski, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00958815
First received: August 12, 2009
Last updated: June 22, 2012
Last verified: June 2012
  Purpose

People with diabetes are at increased risk for atherosclerosis and have high CVD morbidity and mortality rates. Tools for detecting and quantifying atherosclerotic pro/regression in people with diabetes and other CVD risk factors lack sensitivity and specificity for molecular level events that occur during the early stages of atherogenesis. Inflammatory macrophage infiltration in the vessel endothelium is an early, molecular level proatherogenic event. Activated macrophages consume glucose at a high rate. Novel in vivo radiotracer PET/CT techniques have been developed to detect, image and quantify molecular level events like macrophage inflammation and glucose utilization (18FDG) in human vessels. We propose to develop and test this novel technique in the Center for Clinical Imaging Research (CCIR) at WUMS. We propose that HIV-infected people with significant CVD risk profiles are a suitable, unique human model for testing these novel imaging techniques. HIV-infected people taking anti-HIV medications develop insulin resistance, T2DM, dyslipidemia, central adiposity, and hypertension. HIV replicates in macrophages and represents a chronic proinflammatory condition. Recent data indicate that HIV+ CVD risk have greater risk for atherosclerosis and MI than HIV-negative people. To test feasibility, we hypothesize that: a.18FDG-PET/CT imaging will detect more macrophage glucose uptake and inflammation in the carotid and aorta arteries of HIV-infected people with CVD risk than in HIV-negative controls; b. radiotracer PET/CT measures of proatherogenic processes will correlate with carotid intima media thickness; a standard measure of carotid atherosclerotic burden. We propose to obtain pilot data that shows feasibility for a novel analytical approach that will expand capabilities for researchers interested in studying the links between diabetes, inflammation, and CVD in humans.


Condition
Insulin Resistance
Atherosclerosis
Cardiovascular Disease
HIV/AIDS
HIV Infections

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Human Atherosclerotic Plaque Inflammation Imaged Using PDG-PET/CT

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Standard uptake values (SUV) for 18Fluoro-deoxyglucose in the carotid vessels and aorta of HIV-infected people with cardiovascular disease risk factors and compared to the same in HIV-seronegative people with no cardiovascular disease risk factors. [ Time Frame: Baseline ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Carotid intima media thickness measures will be compared to carotid 18FDG SUV. [ Time Frame: Baseline ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: March 2009
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts
HIV-seronegative with no CVD risk factors
Healthy, 35-60 yr old HIV-seronegative men and women with no CVD risk factors (normal fasting glucose tolerance, normal fasting lipid/lipoprotein levels, normotensive, waist circumference <102cm (men) and <88cm (women).
HIV+ with CVD risk factors
35-60 yr old HIV-infected men and women with insulin resistance, dyslipidemia, hypertension, and central adiposity.

  Eligibility

Ages Eligible for Study:   35 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Subjects will be recruited through the AIDS Clinical Trials Unit (ACTU), Washington University Infectious Diseases Clinics, primary care physicians in the community who refer patients to these clinics and Volunteers for Health (VFH).

Criteria

Inclusion Criteria for HIV+ group:

  • confirmed HIV+ status
  • 35-60 years old
  • stable ART for at least the past 4 mos
  • CD4 count >200 cells/µL
  • HIV RNA <40copies/mL
  • fasting glucose=100-126 mg/dL
  • 2hr-oGTT glucose=140-200mg/dL
  • fasting triglycerides >150mg/dL
  • HDL-cholesterol <40mg/dL (men), <50mg/dL (women)
  • resting blood pressure>130/85mmHg
  • waist circumference >102cm(men), >88cm(women)
  • BMI 25-35 kg/m2

For HIV-negative control group:

  • Confirmed HIV negative status
  • 35-60 years old
  • fasting glucose<100mg/dL,
  • 2hr-oGTT glucose<140mg/dL
  • fasting triglycerides<150mg/dL
  • HDL-cholesterol >40mg/dL (men), >50mg/dL(women)
  • normal BP (<130/85mmHg)
  • no central adiposity (waist circ.<102cm(men), <88cm(women)
  • BMI (25-35 kg/m2)

Exclusion Criteria for both groups:

  • history of heart disease, MI, stroke, transient ischemic attack, kidney or liver disease (active hepatitis B or C), dementia
  • statins, fibrates, TZDs, antihypertensives, low dose aspirin, or other prescribed/over-the-counter agents with anti-inflammatory properties
  • cocaine and methamphetamine users
  • serum creatinine >1.5 mg/dL
  • pregnant women
  • cognitive impairment that limits ability to provide voluntary informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00958815

Locations
United States, Missouri
Washington University School of Medicine
St.Louis, Missouri, United States, 63110
Sponsors and Collaborators
Investigators
Principal Investigator: Kevin E Yarasheski, PhD Washington University School of Medicine
  More Information

Additional Information:
Publications:
Yarasheski KE, Laciny E, Overton ET, Reeds DN, Harrod M, Baldwin S, Davila-Roman V. 18FDG PET-CT imaging detects arterial inflammation and early atherosclerosis in HIV-infected adults with cardiovascular disease risk factors. Journal of Inflammation 2012, 9:26 doi:10.1186/1476-9255-9-26.

Responsible Party: Kevin Yarasheski, Professor of Medicine, Cell Biology & Physiology, Physical Therapy, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00958815     History of Changes
Other Study ID Numbers: 18FDG (completed), DK-020579
Study First Received: August 12, 2009
Last Updated: June 22, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
vascular imaging
diabetes
rupture prone plaques
HIV
treatment experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Arteriosclerosis
Atherosclerosis
Cardiovascular Diseases
Inflammation
Insulin Resistance
Plaque, Atherosclerotic
Arterial Occlusive Diseases
Glucose Metabolism Disorders
Hyperinsulinism
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Metabolic Diseases
Pathologic Processes
Pathological Conditions, Anatomical
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Vascular Diseases
Virus Diseases

ClinicalTrials.gov processed this record on November 25, 2014