Effects of Oral Xylitol on Subsequent Energy Intake

Effects of Oral Xylitol on Subsequent Energy Intake, Gastrointestinal Hormones, Glycemic Control, Appetite-related Sensations, and Gastrointestinal Tolerance

The aim of this project is to investigate the effect of xylitol (given as pre-load), compared to sucrose, Ace-K, and water on energy intake during a subsequent ad libitum test meal in healthy participants.

Furthermore, the release of GI hormones, glycemic control, appetite-related sensations, GI tolerance, sweetness and liking in response to the pre-loads will be investigated.

Study Overview

• Status: Active, not recruiting
• Conditions: Gastrointestinal Hormones; Energy Intake; Glycemic Control; Appetite; Satiation
• Intervention / Treatment: Dietary supplement: Xylitol; Dietary supplement: Sucrose; Dietary supplement: Acesulfame Potassium; Dietary supplement: Water

Detailed Description

The subjects will participate in four study days. The screening will last 60 minutes, the study days about 4.5 hours each. After a simple-carbohydrate standard dinner, the subjects have to do an overnight fast until the next morning. Subjects will receive fixed equisweet doses of sucrose (33.5g), xylitol (33.5g), Ace-K (0.1675g), or water as oral pre-loads in a blinded, randomized (counterbalanced) fashion (t = -15 min). Fifteen minutes after the administration (t = 0 min), a standard solid test meal will be presented and ad libitum energy intake will be measured. The end of the test meal will be after 20 minutes or as soon as the subject stops eating for more than 5 minutes. Blood samples (to measure: glycemic control and GI hormones) will be collected at t = -16, t = -1, t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 min and appetite-related sensation rating will be collected at t = -16, t = -1, t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 min. GI symptoms and nausea are assessed at t = -16, -1, 30, 60, 120 and 180 min. At t = -10 min subjects are asked to rate the perceived sweetness and liking of the pre-load and at t = 180 min the perceived liking of the test meal.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4002
    • St. Claraspital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy normal weight participants (10 male and 10 female) with a body-mass index (BMI) of 19.0-24.9 kg/m2
• Age 18-55 years
• Stable body weight (± 5%) for at least three months
• Able to give informed consent as documented by signature

Exclusion Criteria:

• Fructose intolerance
• Pre-existing diet (vegetarian, vegan, sugar free, no breakfast)
• Pre-existing regular consumption of xylitol and/or Ace-K (> 1/week)
• Chronic or clinically relevant acute infections/diseases
• Regular intake of medications, except contraceptives
• Pregnancy: although no contraindication, pregnancy might influence metabolic state.
• Substance abuse (more than 1 glass wine/beer per day; consumption of cannabis, cocaine, heroin, etc.)
• Shift worker
• Participation in another study with investigational drug within the 30 days preceding and during the present study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Xylitol; 20 volunteers receive 33.5g xylitol dissolved in 300mL tap water as an oral pre-load.	Dietary supplement: Xylitol; 33.5g xylitol dissolved in 300mL tap water.; Other Names: E967-Xylitol
Active Comparator: Sucrose; 20 volunteers receive 33.5g sucrose dissolved in 300mL tap water as an oral pre-load.	Dietary supplement: Sucrose; 33.5g sucrose dissolved in 300mL tap water.; Other Names: Saccharose
Active Comparator: Acesulfame Potassium; 20 volunteers receive 0.1675g Ace-K dissolved in 300mL tap water as an oral pre-load.	Dietary supplement: Acesulfame Potassium; 0.1675g Ace-K dissolved in 300mL tap water.; Other Names: E950-Ace-K
Placebo Comparator: Water; 20 volunteers receive 300mL tap water as an oral pre-load.	Dietary supplement: Water; 300mL tap water.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of xylitol on energy intake during a subsequent ad libitum test meal	Fifteen minutes after the administration of the pre-loads (t = 0 minutes), a standard solid test meal will be presented and ad libitum energy intake will be measured.	Total energy intake will be measured from t = 0 until t = 20 minutes or as soon as the as the subject stops eating for more than 5 minutes.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects on GI hormone response - GLP-1	GLP-1 will be quantified using a non-radioactive highly sensitive sandwich ELISA (MSD V-PLEX - #K1503PD) in the presence of a chemiluminescent substrate.	Blood will be drawn at the following time points :t = -16, t = -1 (before the administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load).
Effects on GI hormone response - PYY	PYY-3-36 will be quantified using a non-radioactive high sensitive sandwich ELISA (Millipore - # EZHPYYT66K).	Blood will be drawn at the following time points :t = -16, t = -1 (before the administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load).
Effects on GI hormone response - CCK	Plasma cholecystokinin (CCK) levels will be measured with a sensitive radioimmunoassay using a highly specific antiserum (No. 92128)	Blood will be drawn at the following time points: t = -16, t = -1 (before the administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load).
Effects on GI hormone response - ghrelin	Octanoylated ghrelin will be measured by a radioimmunoassay with 125I [Tyr24] human ghrelin [1-23] as tracer and a rabbit antibody against human ghrelin [1-8] (final dilution 1/100000), which does not cross-react with desoctanoylated ghrelin.	Blood will be drawn at the following time points: t = -16, t = -1 (before the administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load).
Effects on glycemic control - plasma glucose	Glucose will be measured by a glucose oxidase method (Rothen Medizinische Laboratorien AG, Basel, Switzerland).	Blood will be drawn at the following time points: t = -16, t = -1 (before administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load).
Effects on glycemic control - plasma insulin	Insulin will be quantified using a chemiluminescent microparticle immunoassay (chemiflex) reagent kit (#8k41; Abbott) and the relative light units detected by the ARCHITECT optical system (model: CI4100; Abbott).	Blood will be drawn at the following time points: t = -16, t = -1 (before the administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load).
Effects on glycemic control - plasma c-peptide	C-peptide will be measured with a commercially available sandwich ELISA kit from Millipore (Millipore - # EZHCP-20K).	Blood will be drawn at the following time points: t = -16, t = -1 (before administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load).
Effects on glycemic control - plasma glucagon	Glucagon concentrations in plasma will be measured after extraction of plasma with 70% ethanol (vol/vol, final concentration). The antibody is directed against the C-terminus of the glucagon molecule (antibody code no. 4305) and therefore mainly measures glucagon of pancreatic origin.	Blood will be drawn at the following time points: t = -16, t = -1 (before the administration of the pre-load), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-load).
Effects on appetite-related sensations	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.	Visual analogue scales will be recorded at the following time points: t = -16, t = -1 (before the administration of the pre-loads), t = 15, t = 30, t = 60, t = 90, t = 120, t = 150, t = 180 minutes (after the administration of the pre-loads).
Effects on GI tolerance	GI symptoms will be assessed by use of a checklist including the following questions: abdominal pain, nausea, vomiting, diarrhea, borborygmic, abdominal distension, eructation and increased flatus.	GI tolerance will be recorded at t = -16, -1 (before the administration of the pre-load), 30, 60, 120 and 180 minutes (after the administration of the pre-load).
Sweetness of pre-load	Sweetness is assessed by gLMS. General Labeled Magnitude Scales consist of an unequal, vertical line, which is marked with quasi-logarithmic verbal anchors describing different intensities (e.g. "strongest imaginable", "barely detectable"). Participants are instructed to place a mark on the line where their perceived intensity of sensation lies.	Sweetness of the pre-load will be recorded at t = -10 minutes.
Liking ot the pre-load	Liking is assessed by gLMS. General Labeled Magnitude Scales consist of an unequal, vertical line, which is marked with quasi-logarithmic verbal anchors describing different intensities (e.g. "strongest imaginable", "barely detectable"). Participants are instructed to place a mark on the line where their perceived intensity of sensation lies.	Liking of the pre-load will be recorded at t = -10 minutes.
Liking of the test meal	Liking is assessed by gLMS. General Labeled Magnitude Scales consist of an unequal, vertical line, which is marked with quasi-logarithmic verbal anchors describing different intensities (e.g. "strongest imaginable", "barely detectable"). Participants are instructed to place a mark on the line where their perceived intensity of sensation lies.	Liking of the test meal will be recorded at t = 180 minutes.

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Anne Christin Meyer-Gerspach, St. Clara Research Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2023
• Primary Completion (Actual): January 31, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: December 20, 2022
• First Submitted That Met QC Criteria: December 20, 2022
• First Posted (Actual): January 5, 2023

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: PFI-X

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No