ENSO 16 - Study in Healthy Subjects

This is a randomized, double-blind, active-controlled, cross-over study to assess the effect of the sugar substitute "ENSO 16" on glucose metabolism parameters in healthy male or female subjects. 15 healthy subects ≥ 18 years will be included and 30 g of ENSO 16 or 30 g glucose will be orally administered to assess the impact on markers of glucose metabolism. The study medication will be dissolved in 200 mL tap water. After randomization, subjects will receive ENSO 16 (group A) or glucose (group B) on the first study day. Following a wash-out period of at least on week, subjects will receive glucose (group A) or ENSO 16 (group B) on the second study day. A screening examination (inclusion/ exclusion criteria, medical history, etc.) will be done on the first study day before the study medication will be administered. The study medication will be administered after an overnight fast of at least 10h. Subjects will receive a venular cannula and blood is going to be collected at 8 pre-defined timepoints (0 - 15 - 30 - 45 - 60 - 90 - 120 - 180 minutes; 3 min at each time point). In total, 192 mL of blood are going to be collected per study participant. Study participants will also have to fill in a questionnaire to rate gastrointestinal symptoms using a checklist including the following questions: ((a) abdominal pain, (b) nausea, (c) vomiting, (d) diarrhoea, (e) abdominal rumbling, (f) bloating, (g) belching and (h) flatulence. Participants were asked to choose between "no symptom" (0 points), "mild symptoms" (1 point) and "severe symptoms" (2 points) for each question at each time point.

Primary Endpoint To test the effect of orally administered ENSO 16 (30 g) or glucose (30 g) on plasma glucose levels. The area under the curve (AUC) of plasma glucose profiles (0-60 min) will be compared between different study days.

Null and alternative hypotheses:

H0: There is no difference in blood glucose AUC (0-60 min) between glucose and ENSO 16. H1: There is a difference in blood glucose AUC (0-60 min) between glucose and ENSO 16. Sample size calculation No formal sample size calculation could be performed for this trial as ENSO 16 has never been tested on glucose metabolism parameters in a clinical trial. There is evidence that sugar substitutes have to be studied separately because sweeteners differ considerably in their chemical structure and their physiologic effect on glucose metabolism. However, based on a cross-over trial with the sugar substitute xylitol at high doses, a sample size of 12 was appropriate to detect significant differences in outcome parameters. Based on these study results and on available statistical recommendations, a sample size of 15 was chosen, which is considered to be appropriate for this cross over trial to detect significant differences in the main outcome parameters if present. Statistical methodology Calculation of the AUC (0-60 min) for plasma glucose, insulin and Cpeptide profiles. Paired T-tests or Wilcoxon signed rank tests (for skewed distributions) will be applied to describe differences between treatments (glucose and ENSO 16)

Inclusion criteria

• Ability of subject to understand the character and individual consequences of the study;
• Signed informed consent before the start of any specific study procedures;
• Age ≥18 years;
• BMI 18-25 and healthy
• Fasting blood glucose ≤ 100mg/dL (point of care device)

Exclusion criteria

• Substance or alcohol abuse
• Smoking
• Regular intake of medication (except oral contraceptives) including over the counter drugs within 2 weeks before study day 1
• Chronic medical illness
• Food allergies and dietary restrictions
• Pregnancy
• Participation in another clinical trial 3 weeks before study day 1