- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05792137
Postprandial Monocyte Study (PPMS)
Western Human Nutrition Research Center (WHNRC) Postprandial Monocyte Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Monocytes are a heterogeneous population of circulating blood cells that contribute to tissue integrity as well as to innate and adaptive immune defense. There are three well-characterized subsets based on their relative expression of surface antigens, cluster of differentiation 14 (CD14) and cluster of differentiation 16 (CD16). Monocytes originate from myeloid precursors in the bone marrow and enter the circulation as classical monocytes (CLMs). CLMs represent a transient cell population with a diverse differentiation potential. CLMs comprise 80-90% of the circulating blood monocyte pool and remain in circulation for approximately one day before either migrating into tissue to repopulate the tissue resident macrophage population or maturing into non-classical monocytes (NCMs). NCMs comprise only 5-10% of the circulating blood monocyte pool but have a much longer circulating lifespan of approximately 7 days. NCMs exhibit conflicting functions as anti-inflammatory caretakers of vascular tissue and as contributors to the pathogenesis of disease.
Metabolic responses to food consumption influence the risk of cardiometabolic disease. Postprandial glycemia and lipemia modulate vascular health by altering endothelial function and inducing oxidative stress, inflammation, and apoptosis. Consumption of a single high-fat meal increases circulating interleukin 6 (IL-6), enhances expression of monocyte adhesion molecules, reduces flow-mediated dilation, and increases markers of oxidative stress in human subjects. Although NCMs are described as vascular housekeepers with distinct motility and crawling patterns allowing them to actively surveil endothelium and scavenge luminal debris, their role in the postprandial state is currently unknown.
To better understand the function of postprandial NCMs following consumption of a single high-fat mixed macronutrient challenge meal, the investigators propose a study following a crossover design in which participants will consume one of two isocaloric high-fat challenge meals spaced two-weeks apart, a high-saturated fat mixed macronutrient challenge meal or a high-monounsaturated fat mixed macronutrient challenge meal. Blood at fasting and at six hours postprandial will be collected and the proportion of NCMs and their integrin expression will be analyzed by flow cytometry while changes in global gene expression will be measured by RNA-sequencing.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Ryan Snodgrass, PhD
- Phone Number: 530-754-4838
- Email: ryan.snodgrass@usda.gov
Study Contact Backup
- Name: Ellen Bonnel, PhD
- Phone Number: 530-752-4184
- Email: elbonnel@ucdavis.edu
Study Locations
-
-
California
-
Davis, California, United States, 95616
- Recruiting
- USDA Western Human Nutrition Research Center
-
Contact:
- Charles Stephensen, PhD
- Phone Number: 530-304-3528
- Email: charles.stephensen@usda.gov
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- BMI 18.5 - 29.9 kg/m²
- have a bank account and social security number or taxpayer identification for financial compensation
Exclusion Criteria:
- Pregnant or lactating women
- Known allergy or hindering intolerance to study meal ingredients
- Systolic blood pressure greater than 140 mmHg or diastolic blood pressure greater than 90 mmHg measured
- Fasting glucose above 105 mg/dL
- Triglycerides above 150 mg/dL
- HDL cholesterol less than 40 mg/dL (men) and 50 mg/dL (women)
- Self-reported history of difficulties with blood drawing procedures including prior fainting or dizziness, or veins assessed as not suitable for four separate venipunctures by licensed phlebotomist
- Diagnosed active chronic diseases for which the individual is currently taking daily medication, including but not limited to Diabetes mellitus, Cardiovascular disease, Cancer, Gastrointestinal disorders, Kidney disease, Liver disease, Bleeding disorders, Asthma, Autoimmune disorders, Hypertension, Osteoporosis
- Recent minor surgery (within 4 wk) or major surgery (within 16 wk)
- History of gastrointestinal surgery, including gastric bypass surgery or resection
- Recent antibiotic therapy (within 4 wk)
- Known gallbladder disease or history of cholecystectomy
- Recent hospitalization (within 4 wk)
- Use of prescription medications at the time of the study that directly affect endpoints of interest (e.g. hyperlipidemia, glycemic control, steroids, statins, anti-inflammatory agents, and over-the-counter weight loss aids)
- Current participation in another research study
- Less than 18 and over 39 years old
- BMI less than 18.5 and above 29.9 kg/m²
- Has HIV/AIDS or another disease that affects the immune system
- Unable to fast for 12 hours
- Gives regular blood donations and is unwilling to stop during the study
- Has monocytosis (>0.8 x 10³/microliter) or other abnormalities in hematologic parameters based on a screening complete blood count (CBC) with differential
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: High saturated fat challenge meal followed by high mono-unsaturated fat challenge meal
High saturated fat mixed macronutrient challenge meal with palm oil followed by high mono-unsaturated fat mixed macronutrient challenge meal with olive oil two weeks later
|
High saturated fat challenge meal made with palm oil
High mono unsaturated fat challenge meal made with olive oil
|
Experimental: High mono-unsaturated fat challenge meal followed by high saturated fat challenge meal
High mono-unsaturated fat mixed macronutrient challenge meal with olive oil followed by high saturated fat mixed macronutrient challenge meal with palm oil two weeks later
|
High saturated fat challenge meal made with palm oil
High mono unsaturated fat challenge meal made with olive oil
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Monocyte subsets
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Monocyte subsets will be analyzed using flow cytometry.
Subset analysis will be performed by labeling immune cells with anti-cluster of differentiation antigen 45 (anti-CD45), cluster of differentiation antigen 91 (anti-CD91), anti-CD14, and anti-CD16 fluorescently labeled antibodies.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in expression of very late antigen-4
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Monocyte adhesion molecule expression of very late antigen-4 (VLA-4) will be assessed using flow cytometry.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in expression of C-X3-C motif chemokine receptor 1
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Monocyte adhesion molecule expression of C-X3-C motif chemokine receptor 1 (CX3CR1) will be assessed using flow cytometry.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in expression of Notch2
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Monocyte adhesion molecule expression of Notch2 will be assessed using flow cytometry.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in expression of colony stimulating factor 1 receptor
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Monocyte adhesion molecule expression of colony stimulating factor 1 receptor (CSFR1) will be assessed using flow cytometry.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in expression of scavenger receptor class B, member 3
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Monocyte adhesion molecule expression of scavenger receptor class B, member 3 (CD36) will be assessed using flow cytometry.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in intensity of filamentous-actin
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Filamentous-actin (F-actin) intensity will be assessed using phalloidin.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in white blood cell count
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
White blood cell (WBC) count will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in lymphocyte count
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Lymphocyte (LY) count will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in monocyte count
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Monocyte (MO) count will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in change in neutrophil granulocyte count
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Neutrophil granulocyte (NE) count will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in eosinophil count
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Eosinophil (EO) count will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in basophil count
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Basophil (BA) count will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in red blood cell count
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Red blood cell (RBC) count will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in hemoglobin
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Hemoglobin (HGB) will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in hematocrit
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Hematocrit (HCT) will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in mean corpuscular volume
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Mean corpuscular volume (MCV) will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in mean corpuscular hemoglobin
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Mean corpuscular hemoglobin (MCH) will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in mean corpuscular hemoglobin concentration
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Mean corpuscular hemoglobin concentration (MCHC) will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in red blood cell distribution width
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Red blood cell distribution width (RDW) will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in red blood cell distribution width standard deviation
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Red blood cell distribution width standard deviation (RDW-SD) will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in platelet count
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Platelet (PLT) count will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in mean platelet volume
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Mean platelet volume (MPV) will be measured by a DxH 520 Hematology analyzer.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in soluble cluster of differentiation antigen 146
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Endothelial activation including soluble cluster of differentiation antigen 146 (CD146) will be measured by ELISA.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in CD45 gene expression
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Transcriptional changes in non-classical and classical monocytes will be measured by RNA-sequencing following the isolation of non-classical monocytes from peripheral blood by fluorescence-activated cell sorting (FACS) using anti-CD45 fluorescently labeled antibodies.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in CD91 gene expression
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Transcriptional changes in non-classical and classical monocytes will be measured by RNA-sequencing following the isolation of non-classical monocytes from peripheral blood by fluorescence-activated cell sorting (FACS) using anti-CD91 fluorescently labeled antibodies.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in CD14 gene expression
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Transcriptional changes in non-classical and classical monocytes will be measured by RNA-sequencing following the isolation of non-classical monocytes from peripheral blood by fluorescence-activated cell sorting (FACS) using anti-CD14 fluorescently labeled antibodies.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in CD16 gene expression
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Transcriptional changes in non-classical and classical monocytes will be measured by RNA-sequencing following the isolation of non-classical monocytes from peripheral blood by fluorescence-activated cell sorting (FACS) using anti-CD16 fluorescently labeled antibodies.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in levels of interleukin-6
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Plasma markers of systemic inflammation including interleukin-6 will be measured by ELISA.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in levels of interleukin-8
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Plasma markers of systemic inflammation including interleukin-8 will be measured by ELISA.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in levels of C-reactive protein
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Acute phase reactants including C-reactive protein (CRP) will be measured by ELISA.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in levels of serum amyloid A
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Acute phase reactants including serum amyloid A (SAA) will be measured by ELISA.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in levels of chemokine ligand 2
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Chemokines including chemokine ligand 2 will be measured by ELISA.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in levels of 8-isoprostane F2alpha
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Plasma markers of oxidative stress including 8-isoprostane F2alpha will be measured by ELISA.
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in levels of triglycerides
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Lipid-related markers including triglycerides will be measured by auto-analyzer, Cobas Integra 400+ instrument
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in levels of total cholesterol
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Lipid-related markers including total cholesterol will be measured by auto-analyzer, Cobas Integra 400+ instrument
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in levels of HDL-cholesterol
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Lipid-related markers including HDL-cholesterol (HDL-C) will be measured by auto-analyzer, Cobas Integra 400+ instrument
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in levels of LDL-cholesterol
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Lipid-related markers including LDL-cholesterol (LDL-C) will be measured by auto-analyzer, Cobas Integra 400+ instrument
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Change in levels of glucose
Time Frame: Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Plasma glucose will be measured by auto-analyzer, Cobas Integra 400+ instrument
|
Measured from samples taken at 0 hours (fasting) and 6 hours (postprandial) on 2 test days
|
Collaborators and Investigators
Investigators
- Principal Investigator: Ryan Snodgrass, PhD, USDA, Western Human Nutrition Research Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1999385
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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