Effect of Daily Erythritol Versus Sucrose Intake Over 5 Weeks on Glucose Tolerance in Adolescents

Study Overview
=================
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.

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.

Official Title
-----------------
Effect of Daily Erythritol Versus Sucrose Intake Over 5 Weeks on Glucose Tolerance in Adolescents: a Pilot Trial

Conditions
-----------------
Insulin Resistance, Glucose Tolerance, Body Composition, Gastrointestinal Tolerance, Thrombocyte Aggregation, Blood p-Selectin, Blood Erythritol

Intervention / Treatment
-----------------
* Dietary Supplement: Eryhtritol
* Dietary Supplement: Sucrose
* Dietary Supplement: Glucose
* Dietary Supplement: Fructose


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 14 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sucrose<br>15 participants receive 25g sucrose per day during 5 weeks | Dietary Supplement: Sucrose<br>* Sucrose-sweetened beverages twice a day (25g sucrose/day) with main meals during 5 weeks<br>|
| Experimental: Erythritol<br>15 participants receive 36g eryhtritol per day during 5 weeks | Dietary Supplement: Eryhtritol<br>* Eryhtritol-sweetened beverages twice a day (36g erythritol/day) with main meals during 5 weeks EryClot-Pilot: Erythritol 50g dissolved in 300mL water administered once per visit<br>* Other names: E968-Erythritol;|
| Experimental: EryClot-Pilot Erythritol<br>3 participants receive 50g erythritol dissolved in 300mL water once during the visit | Dietary Supplement: Eryhtritol<br>* Eryhtritol-sweetened beverages twice a day (36g erythritol/day) with main meals during 5 weeks EryClot-Pilot: Erythritol 50g dissolved in 300mL water administered once per visit<br>* Other names: E968-Erythritol;|
| Active Comparator: EryClot-Pilot Glucose<br>3 participants receive 75g glucose dissolved in 300mL water once during the visit | Dietary Supplement: Glucose<br>* Glucose 75g dissolved in 300mL water administered once per visit<br>|
| Active Comparator: EryClot-Pilot Fructose<br>3 participants receive 25g fructose dissolved in 300mL water once during the visit | Dietary Supplement: Fructose<br>* Fructose 25g dissolved in 300mL water administered once per visit<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin resistance | Insulin resistance as measured by the HOMA Index. | Change from baseline to 5 weeks after polyol/sucrose intake | 
| EryClot-Pilot Thrombocyte aggregation | Thrombocyte aggregation after consumption of test solution measured with a blood sample | Blood samples at timepoint t= 0, 30, 60, 120, 180 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose tolerance: Insulin | Insulin levels during OGTT | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Glucose tolerance: Glucose | Glucose levels during OGTT | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Glucose tolerance: C-Peptide | C-peptide levels during OGTT | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Glucose tolerance: Glucagon | Glucagon levels during OGTT | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Glucose tolerance: Fructosamin | Fructosamin levels | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Glucose tolerance: HbA1C | HbA1C levels | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Glucose tolerance: Continuous glucose monitoring average | Continuous glucose monitoring for average glucose levels | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Glucose tolerance: Continuous glucose monitoring glucose variability | Continuous glucose monitoring for glucose variability | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Glucose tolerance: Continuous glucose monitoring time within range | Continuous glucose monitoring for time within range | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Glucose absorption | Glucose absorption measured by 3-OMG concetrations during OGTT | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Metabolomics | Metabolomics in plasma, urine and stool samples, measured by 1H-NMR and Liquid Chromatography-Mass Spectrometry (LC-MS). | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Gut microbiota composition | The taxonomic and functional profiles of the gut microbiota (stool samples) assessed by metagenomic shotgun sequencing. | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Gastrointestinal hormones secretion: GLP-1 | Secretion of GLP-1 during OGTT | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Gastrointestinal hormones secretion: PYY | Secretion of PYY during OGTT | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Gastrointestinal hormones secretion: Ghrelin | Secretion of Ghrelin during OGTT | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Gastrointestinal hormones secretion: CCK | Secretion of CCK during OGTT | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Food intake | Food intake assessed with self-reported food records | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Gastrointestinal tolerance | Gastrointestinal tolerance recorded by the Gastrointestinal Symptoms Rating Scale (GSRS), 15 items rated on 7 Point Likert-Scale, a higher score means a worse outcome. Maximum score: 90, Minimum score: 0 | Change from baseline to 3 and 5 weeks after polyol/sucrose intake | 
| Body composition: fat mass | Body composition assessed by mean of bioimpedance analysis: fat mass in kg | Change from baseline to 5 weeks after polyol/sucrose intake | 
| Body composition: fat free mass | Body composition assessed by mean of bioimpedance analysis: fat free mass in kg | Change from baseline to 5 weeks after polyol/sucrose intake | 
| EryClot-Pilot Blood p-Selectin concentrations | Blood p-Selectin concentrations after consumption of test solution | Blood samples at timepoint t= 0, 30, 60, 120, 180 minutes and 24, 48 hours | 
| EryClot-Pilot Blood Erythritol concentrations | Blood Erythritol concentrations after consumption of test solution | Blood samples at timepoint t= 0, 30, 60, 120, 180 minutes and 24, 48 hours |