Investigation of Milk Peptides on Postprandial Blood Glucose Profile

Study Overview
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Brief Summary
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Aim of the study is to investigate the effect of two different dosages of milk peptides on postprandial blood glucose profile in prediabetic subjects compared to placebo. This will be investigated in a cross-over double blind randomized placebo controlled study design. Additionally, long term effects on glucose status, insulin sensitivity and postprandial blood glucose profile will be investigated in a follow up 6-week open label phase with the low dose only.

Official Title
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Investigation of Milk Peptides on Postprandial Blood Glucose Profile: Randomized, Double-blind, Placebo-controlled, Cross-over Study With Different Dosages Followed by an Open-label Single Arm Phase to Estimate Long Term Effects

Conditions
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Postprandial Hyperglycemia

Intervention / Treatment
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* Dietary Supplement: Low dose milk peptide
* Dietary Supplement: High Dose milk peptide
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects with prediabetic HbA1c values between 5.7% - 6.4% and/or Fasting blood glucose ≥ 5.6 mmol/l (≥ 100 mg/dl) und < 7.0 mmol/l (< 125 mg/dl) (in venous plasma) Age: 30-70 years Body mass index 19-35 kg/m2 Non-smoker Caucasian Availability and presence in the study unit for approx. 3.5 hours/ week for 3 times in a row with approx. 1 week of washout in between. 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 Participation in a clinical study with an investigational product within one month before start of study

Ages Eligible for Study
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Minimum Age: 30 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: double blind cross over and open for the phase II of the study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High dose Milk peptides<br>2800mg of whey protein hydrolysates single dose | Dietary Supplement: High Dose milk peptide<br>* what is the effect of milk peptides 2800mg on postprandial glycemia after a meal rich in carbohydrates (75g)<br>|
| Active Comparator: Low dose Milk peptides<br>1400mg of whey protein hydrolysate Single dose and 6 weeks intervention | Dietary Supplement: Low dose milk peptide<br>* what is the effect of milk peptides 1400mg on postprandial glycemia after a meal rich in carbohydrates (75g)<br>|
| Placebo Comparator: Placebo<br>maltodextrin | Dietary Supplement: Placebo<br>* what is the effect of placebo on postprandial glycemia after a meal rich in carbohydrates (75g)<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 | day 1, day 8, day 15, day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum blood glucose concentration | day 1, day 8, day 15, day 57 | 
| Max-Increase | Cmax minus baseline value | day 1, day 8, day 15, day 57 | 
| Tmax | Time to reach maximum blood glucose concentration | day 1, day 8, day 15, day 57 | 
| Tbaseline | First time to reach baseline again after increase or decrease in blood glucose | day 1, day 8, day 15, day 57 | 
| AUC(0-180min): | Total area under curve from 0 to 180 min for blood glucose concentration | day 1, day 8, day 15, day 57 | 
| Insulin-iAUC(0-180min) | Area under the curve calculated as the incremental area under the Insulin response curve, ignoring the area beneath the fasting concentration | day 1, day 8, day 15, day 57 | 
| Cmax Baseline Insulin Max_increase Insulin | Max_increase Insulin Cmax minus baseline insulin value | day 1, day 8, day 15, day 57 | 
| Tmax insulin | time to reach maximum Insulin concentration | day 1, day 8, day 15, day 57 | 
| Fasting glucose, fasting insulin |  | Baseline and Day 57 | 
| HOMA index | Parameters of insulin sensitivity: | Baseline and Day 57 | 
| HbA1c level | HbA1c level after 6 weeks of supplementation | Baseline (V5) and Day 57 (after 6 weeks) | 
| Matsuda index | Insulin sensitivity | Baseline and Day 57 | 
| Quicki Index | Insulin sensitivity | Baseline and Day 57 |