Back to resultsThe Effects of Dietary Erythritol on Platelet Reactivity and Vascular Inflammation (EASI)
Primary Purpose
Platelet Aggregation, Spontaneous, Vascular Thrombosis
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Erythritol
Aspartame
Sponsored by
About this trial
This is an interventional basic science trial for Platelet Aggregation, Spontaneous focused on measuring platelet activation, vascular inflammation, erythritol, aspartame, dietary intervention
Eligibility Criteria
Inclusion Criteria: BMI ≥ 27 kg/m2 Exclusion Criteria: • History of blood clot, transient ischemic attack (TIA), stroke, angina, heart attack, or peripheral vascular disease, or current cancer diagnosis. Pregnant or lactating women Current, prior (within 12 months), or anticipated use of medications for treatment of hyperlipidemia, high blood pressure or diabetes, or any medication that in the opinion of the investigators will confound results. Unwilling to forego the use of anti-inflammatory medication during study. Unwilling to forego the use of marijuana during the study. Use of tobacco. Strenuous exerciser (>4 hours/week at a level more vigorous than walking). Surgery or medication for weight loss. Diet exclusions: Food allergies or dietary restrictions that may undermine compliance to dietary protocol, routine ingestion of more than 2 sugar-sweetened beverages or 2 alcoholic beverage/day. Unwillingness to consume artificial or noncaloric sweeteners. Habitual consumption (>10 gram/day) of beverage or foods that contain erythritol. Recent or current weight loss diet.
Sites / Locations
- Ragle Human Nutrition Research Center, University of California, DavisRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Erythritol-sweetened beverage
Aspartame-sweetened beverage
Arm Description
1-gram erythritol/kg body weight/day, divided into three beverage servings and fruit-flavored with Kool-Aid® unsweetened drink mix.
Control beverages will be made from a noncaloric aspartame-sweetened, fruit-flavored drink mix at the concentration needed to match the sweetness (~3 mg aspartame/kg/day) and flavoring of the erythritol beverages on a per volume basis.
Outcomes
Primary Outcome Measures
P-selectin, a platelet surface marker, assessed as median fluorescence intensity
Change in median fluorescence intensity of P-selectin, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
P-selectin, a platelet surface marker, assessed as percentage of P-selectin positive cells
Change in percentage of P-selectin positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as median fluorescence intensity
Change in median fluorescence intensity of PAC-1, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as percentage of PAC-1 positive cells
Change in percentage of PAC-1 positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Annexin V, a platelet surface marker, assessed as median fluorescence intensity
Change in median fluorescence intensity of annexin V, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Annexin V, a platelet surface marker, assessed as percentage of annexin V positive cells
Change in percentage of annexin V positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Platelet reactivity to physiologic agonist, assessed as change in median fluorescence intensity
The change in median fluorescence intensity induced by physiologic agonists, an index of platelet reactivity, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Platelet aggregation in response to physiologic agonist, assessed as aggregation/min
The change in aggregation/min induced by physiologic agonists will be measured by light transmission aggregometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Platelet aggregation in response to physiologic agonist, assessed as percent of maximum aggregation
The change in % maximum aggregation induced by physiologic agonists will be measured by light transmission aggregometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Platelet-leukocyte interaction, assessed as platelet/leukocyte aggregate size by fluorescence mean intensity
Change in platelet/leukocyte aggregate size, an index of platelet-leukocyte interaction, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Secondary Outcome Measures
Plasma concentration of E-Selectin
Change in plasma E-Selectin in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Plasma concentration of sVCAM1
Change in plasma sVCAM1 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Plasma concentration of sICAM1
Change in plasma sICAM1 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Plasma concentration of D-dimer
Change in plasma D-dimer in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Plasma concentration of Platelet factor 4
Change in plasma platelet factor 4 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Plasma concentration of Fibrinogen
Change in plasma fibrinogen in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Plasma concentration of Prothrombin fragment 1+2
Change in plasma prothrombin fragment 1+2 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Plasma concentration of Plasmin-antiplasmin complex
Change in plasma plasmin-antiplasmin complex in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Plasma concentration of Lp(a)
Change in plasma Lp(a) in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Full Information
NCT ID
NCT05967741
First Posted
June 6, 2023
Last Updated
September 13, 2023
Sponsor
University of California, Davis
1. Study Identification
Unique Protocol Identification Number
NCT05967741
Brief Title
The Effects of Dietary Erythritol on Platelet Reactivity and Vascular Inflammation
Acronym
EASI
Official Title
Randomized Controlled Clinical Trial to Gauge the Effects of Dietary Erythritol on Platelet Reactivity and Vascular Inflammation
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 20, 2023 (Actual)
Primary Completion Date
April 20, 2024 (Anticipated)
Study Completion Date
May 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Davis
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose is to conduct a dietary intervention study in which human participants will consume beverages sweetened with erythritol or aspartame, each for 2 weeks, in a randomized crossover design
Detailed Description
There is a strong correlation between plasma erythritol concentrations and adverse cardiovascular events in high risk individuals. It has also been demonstrated that consumption of dietary erythritol leads to high levels of plasma erythritol. There is in vitro evidence that erythritol at comparable concentrations promotes platelet activation. However, there is no direct evidence that links human consumption of erythritol with the onset of platelet activation and adhesion leading to inflammation. The investigators seek to fill this evidence gap by conducting a randomized crossover dietary intervention study in which human participants will consume beverages sweetened with erythritol or aspartame, each for two weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Platelet Aggregation, Spontaneous, Vascular Thrombosis
Keywords
platelet activation, vascular inflammation, erythritol, aspartame, dietary intervention
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Randomized crossover study with 2-week washout
Masking
ParticipantCare ProviderOutcomes Assessor
Masking Description
Experimental and control beverage are formulated to be similar color, taste and volume.
Allocation
Randomized
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Erythritol-sweetened beverage
Arm Type
Experimental
Arm Description
1-gram erythritol/kg body weight/day, divided into three beverage servings and fruit-flavored with Kool-Aid® unsweetened drink mix.
Arm Title
Aspartame-sweetened beverage
Arm Type
Placebo Comparator
Arm Description
Control beverages will be made from a noncaloric aspartame-sweetened, fruit-flavored drink mix at the concentration needed to match the sweetness (~3 mg aspartame/kg/day) and flavoring of the erythritol beverages on a per volume basis.
Intervention Type
Other
Intervention Name(s)
Erythritol
Other Intervention Name(s)
Noncaloric sugar alcohol
Intervention Description
Erythritol is a naturally occurring and non-nutritive sugar alcohol that is classified as generally recognized as safe (GRAS)
Intervention Type
Other
Intervention Name(s)
Aspartame
Other Intervention Name(s)
Noncaloric sweetener
Intervention Description
Aspartame consists of two amino acids, phenylalanine and aspartic acid, and a methyl group. It does not have metabolic effects and has served as the blinded control beverage in the investigators' completed NIH-funded clinical trials.
Primary Outcome Measure Information:
Title
P-selectin, a platelet surface marker, assessed as median fluorescence intensity
Description
Change in median fluorescence intensity of P-selectin, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Time Frame
6 weeks
Title
P-selectin, a platelet surface marker, assessed as percentage of P-selectin positive cells
Description
Change in percentage of P-selectin positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Time Frame
6 weeks
Title
PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as median fluorescence intensity
Description
Change in median fluorescence intensity of PAC-1, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Time Frame
6 weeks
Title
PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as percentage of PAC-1 positive cells
Description
Change in percentage of PAC-1 positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Time Frame
6 weeks
Title
Annexin V, a platelet surface marker, assessed as median fluorescence intensity
Description
Change in median fluorescence intensity of annexin V, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Time Frame
6 weeks
Title
Annexin V, a platelet surface marker, assessed as percentage of annexin V positive cells
Description
Change in percentage of annexin V positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Time Frame
6 weeks
Title
Platelet reactivity to physiologic agonist, assessed as change in median fluorescence intensity
Description
The change in median fluorescence intensity induced by physiologic agonists, an index of platelet reactivity, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Time Frame
6 weeks
Title
Platelet aggregation in response to physiologic agonist, assessed as aggregation/min
Description
The change in aggregation/min induced by physiologic agonists will be measured by light transmission aggregometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Time Frame
6 weeks
Title
Platelet aggregation in response to physiologic agonist, assessed as percent of maximum aggregation
Description
The change in % maximum aggregation induced by physiologic agonists will be measured by light transmission aggregometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Time Frame
6 weeks
Title
Platelet-leukocyte interaction, assessed as platelet/leukocyte aggregate size by fluorescence mean intensity
Description
Change in platelet/leukocyte aggregate size, an index of platelet-leukocyte interaction, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Plasma concentration of E-Selectin
Description
Change in plasma E-Selectin in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Title
Plasma concentration of sVCAM1
Description
Change in plasma sVCAM1 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Title
Plasma concentration of sICAM1
Description
Change in plasma sICAM1 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Title
Plasma concentration of D-dimer
Description
Change in plasma D-dimer in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Title
Plasma concentration of Platelet factor 4
Description
Change in plasma platelet factor 4 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Title
Plasma concentration of Fibrinogen
Description
Change in plasma fibrinogen in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Title
Plasma concentration of Prothrombin fragment 1+2
Description
Change in plasma prothrombin fragment 1+2 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Title
Plasma concentration of Plasmin-antiplasmin complex
Description
Change in plasma plasmin-antiplasmin complex in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Title
Plasma concentration of Lp(a)
Description
Change in plasma Lp(a) in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Other Pre-specified Outcome Measures:
Title
Plasma concentration of glucose
Description
Change in plasma fasting glucose in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Title
Plasma concentration of triglyceride
Description
Change in plasma fasting triglyceride in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Title
Plasma concentration of cholesterol
Description
Change in plasma fasting cholesterol in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Title
Plasma concentration of low density lipoprotein cholesterol
Description
Change in plasma fasting low density lipoprotein cholesterol in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Title
Plasma concentration of high density lipoprotein cholesterol
Description
Change in plasma fasting high density lipoprotein cholesterol in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Title
Plasma concentration of apolipoprotein B
Description
Change in plasma fasting apolipoprotein B in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Title
Plasma concentration of apolipoprotein CIII
Description
Change in plasma fasting apolipoprotein CIII in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
Title
Plasma concentration of uric acid
Description
Change in plasma fasting uric acid in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
Time Frame
6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
BMI ≥ 27 kg/m2
Exclusion Criteria:
• History of blood clot, transient ischemic attack (TIA), stroke, angina, heart attack, or peripheral vascular disease, or current cancer diagnosis.
Pregnant or lactating women
Current, prior (within 12 months), or anticipated use of medications for treatment of hyperlipidemia, high blood pressure or diabetes, or any medication that in the opinion of the investigators will confound results.
Unwilling to forego the use of anti-inflammatory medication during study.
Unwilling to forego the use of marijuana during the study.
Use of tobacco.
Strenuous exerciser (>4 hours/week at a level more vigorous than walking).
Surgery or medication for weight loss.
Diet exclusions: Food allergies or dietary restrictions that may undermine compliance to dietary protocol, routine ingestion of more than 2 sugar-sweetened beverages or 2 alcoholic beverage/day. Unwillingness to consume artificial or noncaloric sweeteners. Habitual consumption (>10 gram/day) of beverage or foods that contain erythritol. Recent or current weight loss diet.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kimber L. Stanhope, Ph.D.
Phone
5302190914
Email
klstanhope@ucdavis.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Marinelle Nunez, B.S.
Phone
530-752-2146
Email
mvnunez@ucdavis.edu
Facility Information:
Facility Name
Ragle Human Nutrition Research Center, University of California, Davis
City
Davis
State/Province
California
ZIP/Postal Code
95616
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kimber Stanhope, Ph.D.
Phone
530-752-3720
Email
klstanhope@ucdavis.edu
First Name & Middle Initial & Last Name & Degree
Marinelle Nunez, B.S.
Phone
530-752-2146
Email
mvnunez@ucdavis.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
36849732
Citation
Witkowski M, Nemet I, Alamri H, Wilcox J, Gupta N, Nimer N, Haghikia A, Li XS, Wu Y, Saha PP, Demuth I, Konig M, Steinhagen-Thiessen E, Cajka T, Fiehn O, Landmesser U, Tang WHW, Hazen SL. The artificial sweetener erythritol and cardiovascular event risk. Nat Med. 2023 Mar;29(3):710-718. doi: 10.1038/s41591-023-02223-9. Epub 2023 Feb 27.
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The Effects of Dietary Erythritol on Platelet Reactivity and Vascular Inflammation
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