Clinical trial NCT04966299: Effect of Daily Erythritol Versus Sucrose Intake Over 5 Weeks on Glucose Tolerance in Adolescents
Official title: Effect of Daily Erythritol Versus Sucrose Intake Over 5 Weeks on Glucose Tolerance in Adolescents: a Pilot Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Insulin Resistance
Glucose Tolerance
Body Composition
Gastrointestinal Tolerance
Thrombocyte Aggregation
Blood p-Selectin
Blood Erythritol
Blood Xylitol
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2021-07-19
Enrollment: 30
Sex: ALL
Minimum age (years): 14
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: EryClot-Pilot:

This trial is a randomized, double-blind, crossover trial. The project set-up is single-center, national. In total, 3 volunteers will be enrolled. There will be 3 study arms.

EryClot This trial is a randomized single-blind, crossover trial. The project setup is single-center national. In total 10 volunteers will be enrolled. There will be 3 study arms.

EryClot in vitro This trial is an in vitro trial using human blood samples. The project setup is single-center national. In total blood samples from 12 volunteers will be collected.
Primary purpose: PREVENTION

Brief summary: Childhood and adolescence are crucial periods for prevention of obesity, as obese children are five times more likely to be obese at adulthood than lean children. To this purpose, sugar consumption should be reduced. The sugar alcohol erythritol is increasingly popular as sugar substitute in the food industry and is also recommended to diabetic patients. The substance is freely available. Recent acute studies show that erythritol has a positive influence on satiation and gastric emptying without affecting insulin and plasma glucose. In this trial, the investigators aim to assess the effect of a chronic intake of erythritol versus sucrose on insulin resistance in healthy adolescents.

EryClot-Pilot:

Erythritol is also produced by the human body and possibly elevated erythritol levels in the blood are an indication of an increased risk of cardiovascular disease, obesity or diabetes in the future.

In a recently published study, a possible effect of erythritol on blood clotting function was described. In this in vitro experiment, increased blood clotting was observed when erythritol was added to clotting cells (platelets) in the test tube. Studies in humans on blood coagulation after administration of erythritol are missing so far.

With a pilot study, the investigators study whether erythritol is detectable in the blood after administration of glucose and fructose. Furthermore, the erythritol level in the blood and a possible effect on the blood coagulation function after administration of erythritol will be investigated.

These preliminary tests serve to clarify the data situation so that further studies can be based on them.

The preliminary results of the EryClot_Pilot study indicate that there appears to be no measurable effect of erythritol on thrombocyte aggregation. This implicates that there is a discrepancy between our results and the results reported in a recent published study. This is why we need to assess the effects of erythritol administration on more parameters of blood coagulation as well as in more subjects.

Due to a study published in June 2024, there appears the need to investigate the effects of xylitol on blood clotting function as well.

EryClot in vitro:

In addition to the human EryClot study, we will conduct in vitro experiments (aggregometry assay after addition of erythritol or xylitol in human platelet rich plasma).

Detailed description: This trial aims to assess the effects of the daily intake of an erythritol-sweetened beverage over 5 weeks on insulin resistance, glucose tolerance and metabolism as well as on gut microbiota. Moreover, this study will also assess the effect of the above-mentioned intervention on food intake, body composition and gastrointestinal tolerance in this population.

EryClot-Pilot:

The aim of this pilot study is to investigate whether erythritol is detectable in the blood after administration of glucose and fructose. Furthermore, the erythritol level in the blood and a possible effect on the blood clotting function after administration of erythritol will be investigated.

EryClot:

The aim of this study is to investigate the erythritol level in blood after administration of erythritol and a possible effect on blood clotting function. Additionally, a possible effect of xylitol on blood clotting function will be investigated.

EryClot in vitro:

The aim of this study is to investigate the platelet responsiveness in vitro in human plasma after addition of erythritol and xylitol.

Eligibility criteria: EryAdo:

Inclusion Criteria:

* Healthy adolescents
* Aged 14-18 years
* Normal weight (BMI between 15th and 85th percentile for age and gender)
* Minimum weight of 45kg
* Regular sugar consumption \>25g/d

Exclusion Criteria:

* Severe acute or chronic diseases
* Pregnancy
* Regular intake of prebiotics
* Regular intake of probiotics
* Regular intake of pro-/prebiotic foods
* Antibiotics cure within 3 months preceding the present study
* Substance abuse
* Inability to follow procedures due to psychological disorders or insufficient knowledge of project language (German)
* Participation in another study with investigational drug within the 30 days preceding and during the present study.
* Pre-existing regular consumption (\>1/week) of erythritol
* Fructose-intolerance
* Pre-existing diet (vegetarian, vegan, gluten-free, lactose-free, caloric restriction, etc.)

EryClot-Pilot:

3 participants

Inclusion criteria:

* Healthy participants 18-55 years upon inclusion
* Normal weight (BMI between 19.0-24.9 kg/m2)
* Informed consent signed by participant

Exclusion criteria:

* Severe acute or chronic diseases
* Pregnancy: although no contraindication, pregnancy might influence metabolic state. Female adolescents who are pregnant or have the intention to become pregnant during the course of the study are excluded. In female participants a urine pregnancy test is carried out upon screening
* Substance abuse, smoking
* Inability to follow procedures due to psychological disorders or insufficient knowledge of project language (German)
* Participation in another study with investigational drug within the 30 days preceding and during the present study.
* Pre-existing regular consumption (\>1/week) of erythritol
* Fructose-intolerance

EryClot:

Inclusion criteria:

* Healthy participants 18-55 years upon inclusion
* Normal weight (BMI between 19.0-24.9 kg/m2)
* Informed consent signed by participant,

Exclusion criteria:

* Severe acute or chronic diseases
* Pregnancy: although no contraindication, pregnancy might influence metabolic state. Female adolescents who are pregnant or have the intention to become pregnant during the course of the study are excluded. In female participants a urine pregnancy test is carried out upon screening
* Substance abuse, smoking
* Inability to follow procedures due to psychological disorders or insufficient knowledge of project language (German)
* Participation in another study with investigational drug within the 30 days preceding and during the present study.
* Pre-existing regular consumption (\>1/week) of erythritol or xylitol
* Pre-existing impairment of blood coagulation/thrombocyte function (e.g., hereditary, regular intake of anti-coagulant agents (e.g., NSAIDs, heparin, warfarin, etc.))

EryClot in vitro

Inclusion criteria:

* Healthy participants 18-55 years upon inclusion
* BMI \< 30 kg/m2
* Informed consent signed by participant

Exclusion criteria:

* Severe acute or chronic diseases
* Pregnancy: although no contraindication, pregnancy might influence metabolic state. Female adolescents who are pregnant or have the intention to become pregnant during the course of the study are excluded.
* Substance abuse, smoking
* Inability to follow procedures due to psychological disorders
* Participation in another study with investigational drug within the 30 days preceding and during the present study.
* Pre-existing regular consumption (\>1/week) of erythritol or xylitol
* Pre-existing impairment of blood coagulation/thrombocyte function (e.g., hereditary, regular intake of anti-coagulant agents (e.g., NSAIDs, heparin, warfarin, etc.))

Primary outcomes:
measure: Insulin resistance
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: EryClot-Pilot Thrombocyte aggregation
timeFrame: Blood samples at timepoint t= 0, 30, 60, 120, 180 minutes
measure: EryClot Thrombocyte aggregation
timeFrame: Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes
measure: EryClot in vitro: Platelet responsiveness in human platelet rich plasma
timeFrame: One single fasting blood sample at timepoint t = -10 minutes
Secondary outcomes:
measure: Glucose tolerance: Insulin
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Glucose tolerance: Glucose
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Glucose tolerance: C-Peptide
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Glucose tolerance: Glucagon
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Glucose tolerance: Fructosamin
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Glucose tolerance: HbA1C
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Glucose tolerance: Continuous glucose monitoring average
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Glucose tolerance: Continuous glucose monitoring glucose variability
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Glucose tolerance: Continuous glucose monitoring time within range
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Glucose absorption
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Metabolomics
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Gut microbiota composition
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Gastrointestinal hormones secretion: GLP-1
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Gastrointestinal hormones secretion: PYY
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Gastrointestinal hormones secretion: Ghrelin
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Gastrointestinal hormones secretion: CCK
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Food intake
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Gastrointestinal tolerance
timeFrame: Change from baseline to 3 and 5 weeks after polyol/sucrose intake
measure: Body composition: fat mass
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: Body composition: fat free mass
timeFrame: Change from baseline to 5 weeks after polyol/sucrose intake
measure: EryClot-Pilot Blood p-Selectin concentrations
timeFrame: Blood samples at timepoint t= 0, 30, 60, 120, 180 minutes and 24, 48 hours
measure: EryClot-Pilot Blood Erythritol concentrations
timeFrame: Blood samples at timepoint t= 0, 30, 60, 120, 180 minutes and 24, 48 hours
measure: EryClot blood p-selectin concentrations
timeFrame: Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours
measure: EryClot blood sVCAM1 concentrations
timeFrame: Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours
measure: EryClot blood PF4 concentrations
timeFrame: Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours
measure: EryClot blood D-Dimers concentrations
timeFrame: Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours
measure: EryClot blood Erythritol concentrations
timeFrame: Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours
measure: EryClot blood Xylitol concentrations
timeFrame: Blood samples at timepoint t= -60, -1, 30, 60, 120, 180 minutes and 24, 48 hours
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: St. Claraspital
state: Basel-Stadt
Study officials:
affiliation: St. Clara Research Ltd.
name: Bettina K. Wölnerhanssen, PD. MD
role: PRINCIPAL_INVESTIGATOR
References: