Gastrointestinal Tolerance of Erythritol-containing Beverages in Young Children

Study Overview
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Brief Summary
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Purpose of this study: assess the maximum tolerated bolus dose of erythritol, delivered in a clear beverage, compared with placebo (saccharose) in 4-6 year old children.

Detailed Description
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The study is a randomized placebo-controlled, double-blind cross-over trial designed to determine the gastrointestinal (GI) responses and maximum tolerated dose of erythritol in young children as a single oral dose in a beverage in-between meals. The children were divided into 4 dose groups. In each group of children, only one dose level was tested such that each child was exposed to only a single dose level versus placebo. The erythritol dose started at 5 grams and was increased by 10 g between each group of children only if the preceding dose level was found to have no significant GI tolerance effects. The effects on faecal parameters and gastrointestinal complaints were recorded in order to determine the threshold dose. After finding a significant difference in tolerance between erythritol and placebo in the 25 g dose cohort, a protocol amendment was approved allowing the investigators to study a dose of 20 g. Test materials were prepared by Cargill, Vilvoorde, Belgium and supplied in bottles containing 250 mL of a noncarbonated fruit-flavoured (two flavours: strawberry and orange) clear drink sweetened with erythritol at four different dose levels: 5, 15, 20 and 25 g (equivalent to 2, 6, 8 and 10% w/v erythritol, respectively). Placebo was supplied in an identical manner but prepared with common nutritive carbohydrates (saccharose and maltodextrin) and providing an equivalent sweetness to that of the corresponding erythritol beverages (i.e.: 1.4, 4.2, 5.6 and 7% w/v). In total 185 healthy young children aged 4-6 years were recruited at three clinical investigation centres after informed consent of both parents; 184 completed the study.

Official Title
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Gastrointestinal Tolerance of Erythritol-containing Beverages in Young Children

Conditions
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Gastrointestinal, Tolerance

Intervention / Treatment
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* Other: Erythritol drink
* Other: Placebo drink


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Age 4 to 6 years at Study D1 (day of consumption of the first beverage) Body Mass Index ³ 13 kg/m² Accustomed to having breakfast Having a regular defecation frequency inferior or equal to two per day Able to drink 250 mL within 15 minutes Toilet-trained / able to use a potty (both at day and night) Informed consent of both person entitled to parental rights Person entitled to parental rights affiliated to the French social security Exclusion Criteria: Participation in any clinical trial including blood sampling and/or administration of substances up to 90 days before D1 of the study Participation in any non-invasive clinical trial up to 30 days before D1 of this study, including blood sampling and/ or, intravenous, inhalatory administration of substances Having a history of medical or surgical events that may significantly affect the study outcome, such as gastric and digestive diseases Any current metabolic or endocrine disease, including diabetes mellitus Use of medication, including antibiotics, laxatives and steroids Regular gastrointestinal complaints, such as stomach upsets, diarrhoea, constipation, flatulence, abdominal colic

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5 g group<br>5g erythritol dissolved in 250 ml (2% w/v) consumed within 15 min between meals (tested vs. 250 ml isosweet saccharose placebo under same conditions) | Other: Erythritol drink<br> <br> Other: Placebo drink<br> <br> |
| Experimental: 15 g group<br>15g erythritol dissolved in 250 ml (6% w/v) consumed within 15 min between meals (tested vs. 250 ml isosweet saccharose placebo under same conditions) | Other: Erythritol drink<br> <br> Other: Placebo drink<br> <br> |
| Experimental: 25 g group<br>25g erythritol dissolved in 250 ml (10% w/v) consumed within 15 min between meals (tested vs. 250 ml isosweet saccharose placebo under same conditions) | Other: Erythritol drink<br> <br> Other: Placebo drink<br> <br> |
| Experimental: 20 g group<br>20g erythritol dissolved in 250 ml (8% w/v) consumed within 15 min between meals (tested vs. 250 ml isosweet saccharose placebo under same conditions) | Other: Erythritol drink<br> <br> Other: Placebo drink<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diarrhoea and/or significant gastrointestinal (GI) symptoms | Diarrhoea = a single watery stool (Bristol Stool Scale Score of 7) and/or >3 faeces (regardless of consistency) in a 24 h period. Significant GI symptoms = any GI symptoms having a severity recorded as severe intensity in the symptom diary | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stool frequency |  | 48 hours | 
| Stool consistency | Stools were assigned a consistency score using the Bristol Stool Scale | 48 hours | 
| Gastrointestinal symptoms | Occurrence, intensity and frequency of borborygmi, excess flatus, abdominal pain, distended stomach (bloating) and nausea. For vomiting, information collected included occurrence and frequency. Symptom intensity was graded as 0 (none), 1 (mild), 2 (average) and 3 (severe) except for vomiting. | 24 hours | 
| Urinary erythritol excretion | Urine was collected for 24 h after consumption of the test drink and analyzed by HPLC to estimate the proportion absorbed and excreted. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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soft drinks, erythritol, polyol, laxation, gastrointestinal, tolerance, child, diarrhoea