Investigation of Milk Peptides (Pep2Dia®) on Postprandial Blood Glucose Profile in Prediabetic Subjects

Study Overview
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Brief Summary
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The goal is to investigate the 180 min postprandial response on blood glucose and insulin levels after intake of Pep2Dia® in two different dosages compared to placebo in the context of a meal challenge test, providing 75 g of carbohydrates. Pep2Dia® will be administered 15 min prior to a standardized challenge meal.

Detailed Description
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From a previous pilot study (BTS1130/17) there is first evidence that the native whey product with alpha-glucosidase inhibiting properties (Pep2Dia®) has the potential to modulate postprandial hyperglycaemia in prediabetic subjects. Thereby, incremental areas under the curve (iAUC) of glucose as the primary outcome were significantly reduced by a single dosage of 1400 mg Pep2Dia® compared to placebo the second study is to investigate the 180 min postprandial response on blood glucose and insulin levels after intake of Pep2Dia® in two different dosages compared to placebo in the context of a meal challenge test, providing 75 g of carbohydrates. Pep2Dia® will be administered 15 min prior to a standardized challenge meal. Furthermore, the 120 min postprandial incretin response in terms of Glucagon-like Peptide-1 (GLP-1) will be determined. Changes in insulin sensitivity will be determined by the Matsuda-index as appropriate outcome measure.

Official Title
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Investigation of Milk Peptides (Pep2Dia®) on Postprandial Blood Glucose Profile in Prediabetic Subjects: Randomized, Double-blind, Placebo-controlled, Cross-over Study With Different Dosages

Conditions
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Prediabetic State

Intervention / Treatment
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* Dietary Supplement: Pep2dia
* Dietary Supplement: maltodextrin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects (minimum one third of each gender) with prediabetic HbA1c values between 5.7% - 6.4% and/or fasting glucose ≥ 5.6 mmol/L (≥ 100 mg/dL) and < 7.0 mmol/L (< 125 mg/dL) (in venous plasma) (twice confirmed at two independent days if HbA1c is < 5.7%) Body mass index 19-35 kg/m2 Non-smoker Caucasian Availability and presence in the study units for approx. 3.5 hours/ week for 3 times. Signed informed consent form No changes in food habits or physical activity 3 months prior to screening and during the study Exclusion Criteria: Presence of disease or drug(s) influencing digestion and absorption of nutrients or bowel habits Intake of medications known to affect glucose tolerance, e.g., diabetic medication, steroids, protease inhibitors or antipsychotics Diagnosed Typ 2-Diabetics with medical treatment Chronic intake of substances affecting blood coagulation (e.g. acetylic acid (100 mg as standard prophylactic treatment allowed when dose is stable 1 month prior to screening), anticoagulants, diuretics, thiazides (diuretics and thiazides allowed e.g. for hypertension treatment when dose is stable 1 month prior to screening)), which in the Investigator's opinion would impact patient safety Severe liver, renal or cardiac disease Acute gastrointestinal diseases including diarrhea and/or vomiting within the last 2 weeks Known inflammatory and malignant gastrointestinal diseases (i.e. colitis ulcerosa, Morbus Crohn, celiac disease, malignant diseases e.g. colon-cancer, rectum cancer, pancreatitis) Clinically relevant findings as established by medical history, physical examination, clinical laboratory and/or vital signs Major medical or surgical event requiring hospitalization within the previous 3 months Intake of antibiotics within 4 weeks before the test days Known alcohol abuse or drug abuse Pregnant or breast feeding women Known or suspected allergy to any component of the investigational product(s) (e.g. milk protein) Known HIV-infection Known acute or chronic hepatitis B and C infection Blood donation within 4 weeks prior to visit 1 or during the study Subject unable to co-operate adequately

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The study will be performed as a multicentric, randomized, double-blind, and placebo-controlled in a 3-way cross-over design.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pep2dia- dosage 1<br>700mg of whey protein hydrolysates single dose | Dietary Supplement: Pep2dia<br>* what is the effect of Pep2dia on postprandial glycemia after a meal rich in carbohydrates (75g)<br>|
| Active Comparator: Pep2Dia - dosage 2<br>1400mg of whey protein hydrolysates single dose | Dietary Supplement: Pep2dia<br>* what is the effect of Pep2dia on postprandial glycemia after a meal rich in carbohydrates (75g)<br>|
| Placebo Comparator: Placebo<br>maltodextrin single dose | Dietary Supplement: maltodextrin<br>* maltodextrin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose-iAUC(0-180min) | Area under the curve calculated as the incremental area under the blood glucose response curve, ignoring the area beneath the fasting concentration (according to ISO 26642:2010(E) | Day 1, Day 15, Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum blood glucose concentration | Day 1, Day 15, Day 29 | 
| Max_increase | Cmax minus baseline value | Day 1, Day 15, Day 29 | 
| Tmax | Time to reach maximum blood glucose concentration | Day 1, Day 15, Day 29 | 
| Tbaseline | First time to reach baseline again after increase or decrease in blood glucose | Day 1, Day 15, Day 29 | 
| AUC(0-180min) | Total area under curve from 0 to 180 min for blood glucose concentration | Day 1, Day 15, Day 29 | 
| Matsuda index | Marker of insulin sensitivity | Day 1, Day 15, Day 29 | 
| Increase of insulin | Area under the curve calculated as the incremental area under the Insulin response curve, ignoring the area beneath the fasting concentration (Insulin-iAUC(0-180min)). If applicable further pharmacokinetic data from insulin increase will be calculated (e.g. Cmax, Tmax) | Day 1, Day 15, Day 29 | 
| GLP-1-iAUC(0-120min) | 120 min postprandial incretin response in terms of Glucagon-like Peptide-1 | Day 1, Day 15, Day 29 |