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| ID | Type | Description | Link |
|---|---|---|---|
| R01HL153120 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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To determine the mechanism of monocyte priming in humans, the study team will conduct a complete feeding trial in normal weight and metabolically healthy human subjects (20-45 years of age) using a western diet (WD), characterized as being high-saturated fat, high-fructose, and high-calorie for 8 weeks.
The goal is to challenge metabolically healthy human subjects with a high-calorie, Western diet for 8 weeks to identify the metabolite(s) responsible for monocyte priming and use redox proteomics, RNAseq and Chipseq to determine the genes and pathways involved in monocyte priming in humans. To reflect some key components of the typical Western intake, the Study Team will compose the diet to be high in saturated fat (15% of total energy intake) and fructose (14% of total energy intake) with excess energy intake that is 25% higher than estimated total energy expenditure. Participants will complete a run-in phase where weight stability will be achieved on the control diet. No outcome measures will be collected from the run-in phase. After weight is stabilized during the run-in period, participants will enter the experimental phase of the dietary intervention, where overfeeding will begin with additional calories provided by the key nutrients as noted above. Participants will be monitored throughout the feeding trial. After completion of the 8-week overfeeding period, individuals will be allowed to return to a normal dietary intake. All study participants will be given access to counseling for weight reduction should it be needed following the overfeeding period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental diet | Experimental | The experimental diet will provide 15% of calories from saturated fat and 14% of calories from fructose with a goal of providing 1.25x total energy needs |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Experimental diet | Other | Participants that successfully complete the run-in phase will participate in the experimental diet for 8 weeks of feeding. The Participants' adherence will be monitored using direct observation, written daily food diaries, and food waste inventory (i.e., participants are trained to estimate portion of uneaten foods). Participants will be asked to eat one meal onsite 2-3 weekdays (e.g., Monday, Wednesday, and Friday), at which time they will receive meals and snacks for the remainder of that day and enough until the next scheduled visit. |
| Measure | Description | Time Frame |
|---|---|---|
| Measurement of Mitogen-activated Protein Kinase Phosphate 1 (MKP-1) Activity | Analyze plasma from all subjects for their plasma lipid composition using ELISA to quantify MKP-1 protein in blood monocytes. | Baseline (experimental phase) |
| Measurement of Mitogen-activated Protein Kinase Phosphate 1 (MKP-1) Activity | Analyze plasma from all subjects for their plasma lipid composition using ELISA to quantify MKP-1 protein in blood monocytes. | Week 8 (experimental phase) |
| Measure | Description | Time Frame |
|---|---|---|
| Ribonucleic Acid (RNA) Analysis | Determine the genes and pathways involved in monocyte priming in humans. Quantify mRNA expression of all transcripts in expressed monocytes | change in at the endpoint of week 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Measurement of Monocyte Protein S-glutathionylation | To identify which proteins alter their S-glutathionylation status (and possibly their expression levels) in response to HCD-induced monocyte priming, and which signaling pathways are altered in these cells. Isolate S-glutathionylated proteins from all samples and subject them to redox proteomics approach to identify S-glutathionylated proteins and to determine the extent and directionality of modifications on their cysteine residues. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jamy Ard, MD | Wake Forest University Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Wake Forest University Health Sciences | Winston-Salem | North Carolina | 27157 | United States |
Our plan to share materials and manage intellectual property will adhere to the NIH Grant Policy on Sharing of Unique Research Resources including the Sharing of Biomedical Research Resources.
before or immediately after publication
upon request
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| ID | Title | Description |
|---|---|---|
| FG000 | Experimental Diet | The experimental diet will provide 15% of calories from saturated fat and 14% of calories from fructose with a goal of providing 1.25x total energy needs Experimental diet: Participants that successfully complete the run-in phase will participate in the experimental diet for 8 weeks of feeding. The Participants' adherence will be monitored using direct observation, written daily food diaries, and food waste inventory (i.e., participants are trained to estimate portion of uneaten foods). Participants will be asked to eat one meal onsite 2-3 weekdays (e.g., Monday, Wednesday, and Friday), at which time they will receive meals and snacks for the remainder of that day and enough until the next scheduled visit. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Run-In Phase (10-14 Days) |
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| Experimental Phase (8 Weeks) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Experimental Diet | The experimental diet will provide 15% of calories from saturated fat and 14% of calories from fructose with a goal of providing 1.25x total energy needs Experimental diet: Participants that successfully complete the run-in phase will participate in the experimental diet for 8 weeks of feeding. The Participants' adherence will be monitored using direct observation, written daily food diaries, and food waste inventory (i.e., participants are trained to estimate portion of uneaten foods). Participants will be asked to eat one meal onsite 2-3 weekdays (e.g., Monday, Wednesday, and Friday), at which time they will receive meals and snacks for the remainder of that day and enough until the next scheduled visit. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Measurement of Mitogen-activated Protein Kinase Phosphate 1 (MKP-1) Activity | Analyze plasma from all subjects for their plasma lipid composition using ELISA to quantify MKP-1 protein in blood monocytes. | Posted | Mean | Standard Deviation | ng/mg protein | Baseline (experimental phase) |
|
from baseline through week 8
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Experimental Diet | The experimental diet will provide 15% of calories from saturated fat and 14% of calories from fructose with a goal of providing 1.25x total energy needs Experimental diet: Participants that successfully complete the run-in phase will participate in the experimental diet for 8 weeks of feeding. The Participants' adherence will be monitored using direct observation, written daily food diaries, and food waste inventory (i.e., participants are trained to estimate portion of uneaten foods). Participants will be asked to eat one meal onsite 2-3 weekdays (e.g., Monday, Wednesday, and Friday), at which time they will receive meals and snacks for the remainder of that day and enough until the next scheduled visit. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Elena Boudyguina | Advocate Health | 336-713-1411 | Elena.Boudyguina@advocatehealth.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 26, 2024 | Jan 23, 2026 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 25, 2024 | Jan 30, 2025 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
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| change in at the endpoint of week 8 |
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| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Primary | Measurement of Mitogen-activated Protein Kinase Phosphate 1 (MKP-1) Activity | Analyze plasma from all subjects for their plasma lipid composition using ELISA to quantify MKP-1 protein in blood monocytes. | Posted | Mean | Standard Deviation | ng/mg | Week 8 (experimental phase) |
|
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| Secondary | Ribonucleic Acid (RNA) Analysis | Determine the genes and pathways involved in monocyte priming in humans. Quantify mRNA expression of all transcripts in expressed monocytes | Samples not taken for this measure due to lack of funding. No further data/samples will be collected in the future. | Posted | change in at the endpoint of week 8 |
|
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| Other Pre-specified | Measurement of Monocyte Protein S-glutathionylation | To identify which proteins alter their S-glutathionylation status (and possibly their expression levels) in response to HCD-induced monocyte priming, and which signaling pathways are altered in these cells. Isolate S-glutathionylated proteins from all samples and subject them to redox proteomics approach to identify S-glutathionylated proteins and to determine the extent and directionality of modifications on their cysteine residues. | Not Posted | change in at the endpoint of week 8 | Participants |
| 0 |
| 8 |
| 0 |
| 8 |
| 6 |
| 8 |
| Bloating | Gastrointestinal disorders | Systematic Assessment |
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| loose bowel movement | Gastrointestinal disorders | Systematic Assessment |
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| diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| headache | Gastrointestinal disorders | Systematic Assessment |
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