Clinical trial NCT04027283: Acute Effects of the Two Alternative Sweeteners D-allulose and Erythritol on Metabolism
Official title: Acute Effects of the Two Alternative Sweeteners D-allulose and Erythritol on Gastrointestinal Hormone Secretion and Glycemic Control
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Physiological Satiation Mechanisms
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2019-07-19
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of this project is to investigate the effect of intragastric (ig) D-allulose on metabolic parameters in general and to investigate the effect of sweet taste receptor blockade on GI hormone responses, glycemic control, gastric emptying (GE) rates and appetite-related sensations to ig administration of erythritol and D-allulose.

Detailed description: Erythritol (natural non-caloric sweetener) could be an ideal candidate substitute for sugar as it may reduce caloric intake without compensatory overeating or earlier return of hunger. Moreover, it may serve as a physiological tool to disentangle the effects of gastrointestinal (GI) sweet taste receptor stimulation, (an)orexigenic hormone secretion, and glucose metabolism/caloric content on food intake regulation in vivo in humans. However, its effects on appetite, satiation, and satiety have not been studied systematically. Moreover, the mechanisms underlying erythritol-induced anorexigenic GI hormone release have not been investigated so far.

D-allulose is a sugar substitute with almost zero calories and is naturally occurring in small quantities. Apart from its use as sugar replacement, D-allulose seems to favorably affect glycemic control and metabolism as could be shown in animal trials and in a few human trials. However, to date the effects of D-allulose on GI hormone secretion, appetite-related sensations and glycemic control, are not or insufficiently studied in humans.

The aim of this project is therefore to investigate the effect of intragastric (ig) D-allulose on metabolic parameters in general and to investigate the effect of sweet taste receptor blockade on GI hormone responses, glycemic control, gastric emptying (GE) rates and appetite-related sensations to ig administration of erythritol and D-allulose.

Eligibility criteria: Inclusion Criteria:

* Healthy normal weight subjects with a body-mass index of 19.0-24.9
* Normal eating habits (no diets; no dietary changes)
* Age 18-55 years
* Stable body weight for at least three months
* Informed Consent as documented by signature (Appendix Informed Consent Form)

Exclusion Criteria:

* Pre-existing consumption of erythritol or D-allulose on a regular basis (usage of erythritol or D-allulose as sugar replacement; in contrast, erythritol-containing toothpaste is allowed)
* Substance abuse
* Regular intake of medications, except anticonceptives
* Chronic or clinically relevant acute infections
* Pregnancy: although no contraindication, pregnancy might influence metabolic state. Women 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.
* Participation in another study with investigational drug within the 30 days preceding and during the present study.

Primary outcomes:
measure: Effects on GI hormone response - GLP-1
timeFrame: Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
measure: Effects on GI hormone response - PYY
timeFrame: Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
measure: Effects on GI hormone response - ghrelin
timeFrame: Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
measure: Effects on GI hormone response - CCK
timeFrame: Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
measure: Effects on GI hormone response - motilin
timeFrame: Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
Secondary outcomes:
measure: Effects on glycemic control - plasma glucose
timeFrame: Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
measure: Effects on glycemic control - plasma insulin
timeFrame: Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
measure: Effects on glycemic control - plasma c-peptide
timeFrame: Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
measure: Effects on glycemic control - plasma glucagon
timeFrame: Changes from baseline to three hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 90, 120, and 180minutes (after administration).
measure: Effects on gastric emptying rate
timeFrame: Changes from baseline to four hours after treatment. Breath samples will be drawn at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180 and 240minutes (after administration).
measure: Effects on blood lipids
timeFrame: Changes from baseline to two hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 30, 60, and 120minutes (after administration).
measure: Effects on uric acid
timeFrame: Changes from baseline to two hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 30, 60, and 120minutes (after administration).
measure: Effects on hsCRP (high sensitive c-reactive protein)
timeFrame: Changes from baseline to two hours after treatment. Blood will be drawn at the following time points: -10 and -1 minutes (before administration) and 30, 60, and 120minutes (after administration).
measure: Effects on appetite-related sensations
timeFrame: Changes from baseline to four hours after treatment. Visual analogue scales will be recorded at the following time points: -10 and -1 minutes (before administration) and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180 and 240minutes (after administration).
Other outcomes:
measure: Effects on GI tolerance
timeFrame: Changes from baseline to four hours after treatment. GI tolerance will be recorded at time=-10, time=30, time=60, time=90, time=120, time=150, time=180, and time=240minutes.
Locations:
city: Basel
country: Switzerland
facility: St. Claraspital
Study officials:
affiliation: St. Clara Research Ltd.
name: Anne Christin Meyer-Gerspach, PD, PhD
role: PRINCIPAL_INVESTIGATOR
References: