Clinical trial NCT05967741: The Effects of Dietary Erythritol on Platelet Reactivity and Vascular Inflammation
Official title: Randomized Controlled Clinical Trial to Gauge the Effects of Dietary Erythritol on Platelet Reactivity and Vascular Inflammation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Platelet Aggregation, Spontaneous
Vascular Thrombosis
Keywords: platelet activation
vascular inflammation
erythritol
aspartame
dietary intervention
Lead sponsor: University of California, Davis
Sponsor class: OTHER
First posted: 2023-08-01
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized crossover study with 2-week washout
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: P-selectin, a platelet surface marker, assessed as median fluorescence intensity
timeFrame: 6 weeks
measure: P-selectin, a platelet surface marker, assessed as percentage of P-selectin positive cells
timeFrame: 6 weeks
measure: PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as median fluorescence intensity
timeFrame: 6 weeks
measure: PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as percentage of PAC-1 positive cells
timeFrame: 6 weeks
measure: Annexin V, a platelet surface marker, assessed as median fluorescence intensity
timeFrame: 6 weeks
measure: Annexin V, a platelet surface marker, assessed as percentage of annexin V positive cells
timeFrame: 6 weeks
measure: Platelet reactivity to physiologic agonist, assessed as change in median fluorescence intensity
timeFrame: 6 weeks
measure: Platelet aggregation in response to physiologic agonist, assessed as aggregation/min
timeFrame: 6 weeks
measure: Platelet aggregation in response to physiologic agonist, assessed as percent of maximum aggregation
timeFrame: 6 weeks
measure: Platelet-leukocyte interaction, assessed as platelet/leukocyte aggregate size by fluorescence mean intensity
timeFrame: 6 weeks
Secondary outcomes:
measure: Plasma concentration of E-Selectin
timeFrame: 6 weeks
measure: Plasma concentration of sVCAM1
timeFrame: 6 weeks
measure: Plasma concentration of sICAM1
timeFrame: 6 weeks
measure: Plasma concentration of D-dimer
timeFrame: 6 weeks
measure: Plasma concentration of Platelet factor 4
timeFrame: 6 weeks
measure: Plasma concentration of Fibrinogen
timeFrame: 6 weeks
measure: Plasma concentration of Prothrombin fragment 1+2
timeFrame: 6 weeks
measure: Plasma concentration of Plasmin-antiplasmin complex
timeFrame: 6 weeks
measure: Plasma concentration of Lp(a)
timeFrame: 6 weeks
Other outcomes:
measure: Plasma concentration of glucose
timeFrame: 6 weeks
measure: Plasma concentration of triglyceride
timeFrame: 6 weeks
measure: Plasma concentration of cholesterol
timeFrame: 6 weeks
measure: Plasma concentration of low density lipoprotein cholesterol
timeFrame: 6 weeks
measure: Plasma concentration of high density lipoprotein cholesterol
timeFrame: 6 weeks
measure: Plasma concentration of apolipoprotein B
timeFrame: 6 weeks
measure: Plasma concentration of apolipoprotein CIII
timeFrame: 6 weeks
measure: Plasma concentration of uric acid
timeFrame: 6 weeks
Locations:
city: Davis
country: United States
facility: Ragle Human Nutrition Research Center, University of California, Davis
state: California
Study officials:
References:
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.