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Lipid Challenge in Adults

Not Applicable
Completed
Conditions
Cardiovascular Diseases
Interventions
Dietary Supplement: Lipid Challenge
Registration Number
NCT03948295
Lead Sponsor
Emory University
Brief Summary

Participants in this study will have one visit to the Emory University Hospital Clinical Research Unit. Participants will consume, over 5 minutes, a single standardized fat challenge (100 grams), using a commercially available liquid high-energy long chain triglyceride fat emulsion (Calogen), which provides 50 grams of long chain triglycerides per 100 mL. Participants will have 20 mL blood withdrawn at six successive time points over an 8-hour period, where the first time point after fasting (baseline) is followed by 5 time-points after fat consumption. Blood will be analyzed for a wide panel of blood lipids.

Detailed Description

Cardiovascular disease (CVD) is the leading killer of Americans, accounting more than 800,000 deaths each year. A vital step in reducing the number of heart disease-related deaths in the U.S. is to identify those at probable risk. The Clinical Chemistry Branch (CCB) in the Division of Laboratory Sciences (DLS) at the Centers for Disease Control and Prevention (CDC) has developed advanced analytical methods for assessing the risk for lipid metabolism related diseases, including CVD. CCB of the CDC has developed a comprehensive analytical method to measure levels of protein and lipid constituents of lipoprotein size/density classes (e.g. high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) in blood. CCB plans to eventually apply this method in future investigations of cohorts with different CVD states. The measurement of this wide array of CVD-linked biomarkers has the potential to improve the assessment of CVD risk over current clinical methods based on lipoprotein classes.

However, limited information is available about how the advanced tests developed by CCB are affected by blood collection conditions, such as fasting/non-fasting state of the subjects. The purpose of this study is to determine the relative significance of these pre-analytical variables and determine optimal conditions for future cohort studies.

This study will recruit up to 32 healthy individuals, with and without obesity, to participate. The study involves one visit to the Emory University Hospital Clinical Research Unit where participants will consume, over 5 minutes, a single standardized fat challenge (100 grams), using a commercially available liquid high-energy long chain triglyceride fat emulsion (Calogen; http://www.nutricia.ie/calogen#), which provides 50 grams of long chain triglycerides per 100 mL. Participants will have 20 mL blood withdrawn at six successive time points over an 8-hour period, where the first time point after fasting is followed by 5 time-points after fat (Calogen) consumption. Blood will be analyzed at the CCB for a wide panel of blood lipids and potential biomarkers for CVD.

Specific expected outcomes of the study include the following: 1) Determination of typical intra-individual differences between fasting and post-prandial states; and 2) Changes in the levels of the various analytes after fat consumption will be indicative of inter-individual differences in the rate of triglyceride depletion, and the rate of accumulation/depletion of HDL or LDL of different particle size range and composition. The results will allow the assessment of significant differences in lipid metabolism between individuals with a normal BMI (20 to 25 kg/m\^2) versus those with a BMI in the obese range (30-35 kg/m\^2).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
32
Inclusion Criteria
  • functionally ambulatory
  • BMI between >20 to 40 kg/m^2
  • available for an 8 hour visit to the Emory University Hospital Clinical Research Center
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Exclusion Criteria
  • has taken any diabetic or lipid lowering prescription medications within the past 12 months
  • history of chronic diseases
  • hospitalized within the last year
  • currently pregnant
  • current active malignant neoplasm or history of malignancy (other than localized basal cell cancer of the skin) during the previous 5 years
  • current chronic autoimmune or pro-inflammatory disease
  • history of tuberculosis, HIV, or other chronic infection
  • previous diagnosis of type 1 or type 2 diabetes with active treatment with insulin or other glucose lowering medication
  • advanced (>= stage 3) renal disease
  • recreational or prescription drug or alcohol abuse
  • any history of gastrointestinal diseases, including malabsorption
  • any history of intolerance to dietary fat
  • inability to provide informed consent
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Lipid Challenge InterventionLipid ChallengeParticipants of all weights will receive the lipid challenge intervention.
Primary Outcome Measures
NameTimeMethod
Change in Free CholesterolHours 0, 0.5, 1, 2, 4, and 6

Free cholesterol concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI. Free cholesterol is unesterified cholesterol that is circulating in the blood stream.

Change in Total CholesterolHours 0, 0.5, 1, 2, 4, and 6

Total cholesterol profiles for each time-point will be compared between participants with normal BMI and participants with obese range BMI. Elevated total cholesterol has been thought to contribute to atherosclerotic events, however, research has also observed coronary events occurring in individuals with total cholesterol levels in the acceptable range.

Change in Phospholipid Transfer ProteinHours 0, 0.5, 1, 2, 4, and 6

Phospholipid transfer protein concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in Serum Amyloid A1Hours 0, 0.5, 1, 2, 4, and 6

Serum amyloid A1 concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in low-density lipoprotein (LDL) SizeHours 0, 0.5, 1, 2, 4, and 6

LDL concentration size profiles for each time-point will be compared between participants with normal BMI and participants with obese range BMI. LDL is considered to be atherogenic because it is likely to be trapped inside the intima of blood vessels and arteries and initiate inflammatory response, foam-cell formation, and smooth muscle cell proliferation, leading to development necrotic cores, lesions, plaques and their eventual rupture. Elevated LDL has been thought to contribute to atherosclerotic events, however, research has also observed coronary events occurring in individuals with LDL levels in the acceptable range.

Change in PhosphatidylethanolamineHours 0, 0.5, 1, 2, 4, and 6

Phosphatidylethanolamine concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in SphingomyelinHours 0, 0.5, 1, 2, 4, and 6

Sphingomyelin concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in Apolipoprotein AIIHours 0, 0.5, 1, 2, 4, and 6

Apolipoprotein AII concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in Apolipoprotein AIVHours 0, 0.5, 1, 2, 4, and 6

Apolipoprotein AIV concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in Apolipoprotein BHours 0, 0.5, 1, 2, 4, and 6

Apolipoprotein B concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in Serum Paraoxonase/arylesterase 1Hours 0, 0.5, 1, 2, 4, and 6

Serum paraoxonase/arylesterase 1 concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in high-density lipoprotein (HDL) SizeHours 0, 0.5, 1, 2, 4, and 6

HDL concentration size profiles for each time-point will be compared between participants with normal BMI and participants with obese range BMI. HDL is considered to be anti-atherogenic because of its ability deplete excess cholesterol accumulating necrotic cores and repair arterial lesions.

Change in TriglyceridesHours 0, 0.5, 1, 2, 4, and 6

Triglyceride concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI. Triglycerides peak in serum 2 to 4 hours after a meal and return to a pre-meal state in 6 to 8 hours.

Change in LysophosphatidylcholineHours 0, 0.5, 1, 2, 4, and 6

Lysophosphatidylcholine concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in Cholesterol Ester Transfer ProteinHours 0, 0.5, 1, 2, 4, and 6

Cholesterol ester transfer protein concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in Cholesterol EsterHours 0, 0.5, 1, 2, 4, and 6

Cholesterol ester concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI. Lipoproteins contain cholesterol ester, and cholesterol ester is associated with atherosclerosis.

Change in PhosphatidylinositolHours 0, 0.5, 1, 2, 4, and 6

Phosphatidylinositol concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in PhosphatidylcholineHours 0, 0.5, 1, 2, 4, and 6

Phosphatidylcholine concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in Apolipoprotein AIHours 0, 0.5, 1, 2, 4, and 6

Apolipoprotein AI concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in Apolipoprotein CIIHours 0, 0.5, 1, 2, 4, and 6

Apolipoprotein CII concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in Apolipoprotein CIIIHours 0, 0.5, 1, 2, 4, and 6

Apolipoprotein CIII concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in Lecithin-Cholesterol AcyltransferaseHours 0, 0.5, 1, 2, 4, and 6

Lecithin-cholesterol acyltransferase concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in Lipoprotein (a)Hours 0, 0.5, 1, 2, 4, and 6

Lipoprotein (a) concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in Apolipoprotein CIHours 0, 0.5, 1, 2, 4, and 6

Apolipoprotein CI concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in Apolipoprotein EHours 0, 0.5, 1, 2, 4, and 6

Apolipoprotein E concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Change in Serum Amyloid A4Hours 0, 0.5, 1, 2, 4, and 6

Serum amyloid A4 concentration for each time-point will be compared between participants with normal BMI and participants with obese range BMI.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Emory University Hospital

🇺🇸

Atlanta, Georgia, United States

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