Clinical trial NCT02016703: Gastrointestinal Tolerance of Erythritol-containing Beverages in Young Children
Official title: Gastrointestinal Tolerance of Erythritol-containing Beverages in Young Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gastrointestinal
Tolerance
Keywords: erythritol
polyol
laxation
gastrointestinal
tolerance
soft drinks
child
diarrhoea
Lead sponsor: Cargill
Sponsor class: INDUSTRY
Collaborators: name: Biofortis Mérieux NutriSciences
First posted: 2013-12-20
Enrollment: 185
Sex: ALL
Minimum age (years): 4
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Diarrhoea and/or significant gastrointestinal (GI) symptoms
timeFrame: 48 hours
Secondary outcomes:
measure: Stool frequency
timeFrame: 48 hours
measure: Stool consistency
timeFrame: 48 hours
measure: Gastrointestinal symptoms
timeFrame: 24 hours
measure: Urinary erythritol excretion
timeFrame: 24 hours
Other outcomes:
Locations:
city: Bron
country: France
facility: Clinical Investigation Centre Louis Pradel Hospital
city: Nantes
country: France
facility: Biofortis Merieux NutriSciences
city: Paris
country: France
facility: Clinical Investigation Centre Robert Debré Hospital
Study officials:
affiliation: Clinical Investigation Centre Robert Debré Hospital, Paris, France
name: Evelyne Jacqz-Aigrain, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bornet FR, Blayo A, Dauchy F, Slama G. Plasma and urine kinetics of erythritol after oral ingestion by healthy humans. Regul Toxicol Pharmacol. 1996 Oct;24(2 Pt 2):S280-5. doi: 10.1006/rtph.1996.0109.
citation: Arrigoni E, Brouns F, Amado R. Human gut microbiota does not ferment erythritol. Br J Nutr. 2005 Nov;94(5):643-6. doi: 10.1079/bjn20051546.
citation: Bornet FR, Blayo A, Dauchy F, Slama G. Gastrointestinal response and plasma and urine determinations in human subjects given erythritol. Regul Toxicol Pharmacol. 1996 Oct;24(2 Pt 2):S296-302. doi: 10.1006/rtph.1996.0111.
citation: Tetzloff W, Dauchy F, Medimagh S, Carr D, Bar A. Tolerance to subchronic, high-dose ingestion of erythritol in human volunteers. Regul Toxicol Pharmacol. 1996 Oct;24(2 Pt 2):S286-95. doi: 10.1006/rtph.1996.0110.
citation: Munro IC, Berndt WO, Borzelleca JF, Flamm G, Lynch BS, Kennepohl E, Bar EA, Modderman J. Erythritol: an interpretive summary of biochemical, metabolic, toxicological and clinical data. Food Chem Toxicol. 1998 Dec;36(12):1139-74. doi: 10.1016/s0278-6915(98)00091-x.
citation: Storey D, Lee A, Bornet F, Brouns F. Gastrointestinal tolerance of erythritol and xylitol ingested in a liquid. Eur J Clin Nutr. 2007 Mar;61(3):349-54. doi: 10.1038/sj.ejcn.1602532. Epub 2006 Sep 20.
citation: Lifshitz F, Ament ME, Kleinman RE, Klish W, Lebenthal E, Perman J, Udall JN Jr. Role of juice carbohydrate malabsorption in chronic nonspecific diarrhea in children. J Pediatr. 1992 May;120(5):825-9. doi: 10.1016/s0022-3476(05)80260-4. No abstract available.
citation: Lewis SJ, Heaton KW. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997 Sep;32(9):920-4. doi: 10.3109/00365529709011203.