Clinical trial NCT05087823: The Mixed Meal Challenge Study
Official title: Measurements of Lipoproteins, Apolipoproteins, and Lipids in Three Separate Oral Challenges - Fat, Sugar, and Mixed Test Meals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Diseases
Hyperlipidemias
Keywords: Prevention
Hyperlipidemia
Cardiovascular disease
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
First posted: 2021-10-21
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess sample collection conditions for various dietary challenges (fat, sugar, and mixed) and determine the optimal fasting and post-meal sample collection time points for future studies on a larger group of individuals. Study participants will attend three study visits where they take part in lipid, glucose, and mixed meal challenges. At each of the three visits, participants will provide venous blood samples and a urine sample before consuming the test meal and will provide 6 additional venous finger blood samples post-meal.

Detailed description: Cardiovascular disease (CVD) is the leading killer of Americans, accounting for 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. This comprehensive analytical method measures levels of protein and lipid constituents of lipoprotein size and density classes (e.g. high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL)) in blood. The analytical method uses asymmetric flow-field flow fractionation (AF4) to separate lipoprotein classes (HDL, LDL, VLDL) in serum or plasma into size fractions, and in each fraction quantifies over 50 CVD-linked biomarkers by isotope dilution tandem mass spectrometry. The CCB plans to apply the measurement of this wide array of biomarkers in future epidemiologic investigations of CVD. These studies have the potential to expand the number of diagnostically relevant CVD risk factors that currently are limited to cholesterol and triglyceride measurements.

However, there is limited information about how the CVD-linked biomarkers measured with the CCB's method are affected by blood collection conditions and the fasting/non-fasting state of individuals. Furthermore, lipid metabolism is very dynamic and the absolute levels of biomarkers are strongly affected by each individual's diet, lifestyle, gender, age, and physiology. Thus, assessing biomarkers related to lipid metabolism is most effective in a pre- and post-test comparison (i.e. fasting vs. after a test meal) with controlled lipid and carbohydrate content.

The study involves three different meal challenges on three separate days with approximately two weeks in between. The first meal challenge will involve the consumption of a standardized mixture of dietary fats (lipid challenge), the second meal challenge will be a sugar sweetened beverage (glucose challenge) and the third meal challenge will be a nutrition shake (mixed meal challenge). At each of the three visits, each individual will provide both venous and finger-prick blood samples and a urine sample before consuming the test meal (in a fasting state) and 6 additional venous and finger-prick blood samples post-meal at described intervals. Each study visit will last approximately 8 hours.

Eligibility criteria: Inclusion Criteria:

Any adult (18 -50 years) may participate who agrees to complete the following requirements:

* Be functionally ambulatory
* Have a body mass index (BMI) between \>20 kg/m2 to \<40 kg/m2
* Be available for an 8-hour visit to the Emory University Hospital Clinical Research Center
* Be able to fast for 10 hours prior to visiting Emory University Hospital Clinical Research Unit for each meal challenge

Exclusion Criteria:

* Vulnerable populations which include children, pregnant women, individuals with mental disabilities, and prisoners will be excluded from the study.
* Individuals with history of GI symptoms or fat intolerance will be excluded from the study.
* Individuals with health condition that would put them in risk due to 10 hour fasting, including:

  1. Has taken any diabetic or lipid lowering prescription medications within the past 12 months
  2. History of chronic diseases
  3. Hospitalized within the last year
  4. Currently pregnant
  5. Current active malignant neoplasm or history of malignancy (other than localized basal cell cancer of the skin) during the previous 5 years
  6. Current chronic autoimmune or pro-inflammatory disease
  7. History of tuberculosis, HIV, or other chronic infection
  8. Previous diagnosis of type 1 or type 2 diabetes with active treatment with insulin or other glucose lowering medication
  9. Advanced (\>= stage 3) renal disease
  10. Recreational or prescription drug or alcohol abuse
  11. Any history of gastrointestinal diseases, including malabsorption
  12. Any history of intolerance to dietary fat
  13. Inability to provide informed consent

Primary outcomes:
measure: Change in high-density lipoprotein (HDL) Size
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in low-density lipoprotein (LDL) Size
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Total Cholesterol
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Free Cholesterol
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Cholesterol Ester
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Triglycerides
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Phosphatidylinositol
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Phosphatidylethanolamine
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Phosphatidylcholine
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Sphingomyelin
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Lysophosphatidylcholine
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Apolipoprotein AI
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Apolipoprotein AII
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Apolipoprotein AIV
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Apolipoprotein B
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Apolipoprotein CI
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Apolipoprotein CII
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Apolipoprotein CIII
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Apolipoprotein E
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Lecithin-Cholesterol Acyltransferase
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Cholesterol Ester Transfer Protein
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Lipoprotein (a)
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Phospholipid Transfer Protein
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Serum Paraoxonase/arylesterase 1
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Serum Amyloid A1
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
measure: Change in Serum Amyloid A4
timeFrame: Baseline, Minute 15, Minute 30, Hour 1, Hour 2, Hour 4 and Hour 6 during study visits 1, 2, and 3 (up to 6 weeks)
Secondary outcomes:
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Thomas Ziegler, MD
role: PRINCIPAL_INVESTIGATOR
References: