Physiological Satiation Mechanisms
Conditions
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.
Interventions
DIETARY_SUPPLEMENTErythritol
50g erythritol dissolved in 300mL tap water
DIETARY_SUPPLEMENTErythritol + lactisole
50g erythritol + lactisole (450ppm) dissolved in 300mL tap water
DIETARY_SUPPLEMENTD-allulose
25g D-allulose dissolved in 300mL tap water
DIETARY_SUPPLEMENTD-allulose + lactisole
25g D-allulose + lactisole (450ppm) dissolved in 300mL tap water
DIETARY_SUPPLEMENTTap water
300mL tap water
DIETARY_SUPPLEMENTTap water + lactisole
300mL tap water + lactisole (450ppm)
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effects on GI hormone response - motilin | 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). | Plasma motilin levels will be measured with a sensitive radioimmunoassay as previously described using 125I \[Nle13\] human motilin as tracer and rabbit anti-human Nle13 motilin antibody (final dilution 1/12000). |
| Effects on GI hormone response - GLP-1 | 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). | Plasma GLP-1 will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA). |
| Effects on GI hormone response - PYY | 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). | Plasma PYY, and ghrelin will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA). |
| Effects on GI hormone response - ghrelin | 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). | Plasma ghrelin will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA). |
| Effects on GI hormone response - CCK | 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). | Plasma cholecystokinin (CCK) levels will be measured with a sensitive radioimmunoassay using a highly specific antiserum. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effects on gastric emptying rate | 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). | Gastric emptying rate will be determined using a 13C-sodium acetate breath test. |
| Effects on blood lipids | 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). | Analyses of blood lipids are carried out in the hospital laboratory. |
| Effects on hsCRP (high sensitive c-reactive protein) | 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). | Analyses of hsCRP are carried out in the hospital laboratory. |
| Effects on appetite-related sensations | 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). | Appetite perceptions (feelings of: a) hunger, b) satiety) are assessed by visual analogue scale (VAS). Visual analogue scales consist of a horizontal, unstructured, 10-cm line representing the minimum (0.0 points) to the maximum rating (10.0 points). Subjects assign a vertical mark across the line to indicate the magnitude of their subjective sensation at the present time point. The measurement is quantified by the distance from the left end of the line (minimum rating) to the subject's vertical mark. |
| Effects on uric acid | 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). | Analyses of uric acid are carried out in the hospital laboratory. |
| Effects on glycemic control - plasma glucose | 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). | Blood glucose concentrations will be measured by a commercial hexokinase-glucose-6-phosphate-dehydrogenase method (Roche, Basel, Switzerland). Insulin, c-peptide and glucagon will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA). The lowest level of insulin that can be detected by this assay is 87 pg/mL when using a 25 µL sample. The lowest level of c-peptide that can be detected by this assay is 9.5 pg/mL when using a 25 µL sample. The lowest level of glucagon that can be detected by this assay is 13 pg/mL when using a 25 µL sample. The intra-assay coefficient of variation for all peptides (insulin, c-peptide and glucagon) is below 10%, whereas the inter-assay coefficient of variation is below 15%. |
| Effects on glycemic control - plasma insulin | 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). | Insulin will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA). The lowest level of insulin that can be detected by this assay is 87 pg/mL when using a 25 µL sample. The intra-assay coefficient of variation for insulin is below 10%, whereas the inter-assay coefficient of variation is below 15%. |
| Effects on glycemic control - plasma c-peptide | 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). | C-peptide will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA). The lowest level of c-peptide that can be detected by this assay is 9.5 pg/mL when using a 25 µL sample. The intra-assay coefficient of variation for c-peptide is below 10%, whereas the inter-assay coefficient of variation is below 15%. |
| Effects on glycemic control - plasma glucagon | 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). | Glucagon will be measured with a commercially available immunoassay kit (MILLIPLEX® MAP; Millipore Corporation, Billerica, MA, USA). The lowest level of glucagon that can be detected by this assay is 13 pg/mL when using a 25 µL sample. The intra-assay coefficient of variation for glucagon is below 10%, whereas the inter-assay coefficient of variation is below 15%. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Effects on GI tolerance | 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. | GI symptoms will be assessed by use of a checklist including the following questions: abdominal pain, nausea, vomiting, diarrhoea, borborygmi, abdominal distension, eructation and increased flatus. |
Countries
Switzerland
Outcome results
None listed