Trial document





This trial has been registered retrospectively.
drksid header

  DRKS00005682

Trial Description

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Title

Effect of different milk fractions on the metabolic response in healthy and prediabetic volunteers

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Trial Acronym

MIPROMET

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URL of the Trial

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Brief Summary in Lay Language

Casein and whey proteins are the main milk proteins. Cheese is essentially a concentration of the major milk protein casein resulting from coagulation while whey proteins remain in the cheese whey. Glycomacropeptides also occur during cheesemaking. They are found in the cheese whey and isolated out of it.
In the gastrointestinal tract casein forms into a gel which could delay gastric emptying. This way the transit time in the gut is prolonged which could improve the intake of protein components. Furthermore it results in a lower and steady rise of blood glucose. Whey proteins on the other hand are handled by the stomach like fluids. They seem to increase the release of insulin and thereby have a positive effect on glucose metabolism.
The aim of this study is to investigate the effects of different milk fractions on the metabolic response in healthy and prediabetic humans.
The test drinks consist of either 50g whey protein isolate, 50g casein, or 50g GMP and 50g maltodextrin19, 2g Hydroxyproline or 1g acetaminophen, 10g lactulose and aroma or of only 50g maltodextrin 19, 2g Hydroxyproline or 1g acetaminophen and 10g lactulose and aroma which is mixed with 300 ml room-tempered water.(healthy volunteers arms 1 to 4; prediabetic volunteers arms 5 to 8)
A venous line will be inserted in a forearm vein to collect blood after 0, 15, 30, 45, 60, 90, 120, 180 and 240 min and blood glucose will be analyzed immediately. The feeling of hunger will be assessed by a visual analogue scale every hour. Lactulose is a non-absorbable ingredient and is fermented by bacteria in the colon whereby hydrogen is formed. To assess the transit time, hydrogen air will be measured in the exhalation air every half hour. Acetaminophen (marker for gastric emptying), GIP, GLP-1, insulin, C-peptide, glucagon, ghrelin, dipeptidylpeptidase IV, amino acids, acylcarnitines and phospholipids will be analyzed in the plasma.
An amendment has been submitted (5/24/2014) stating that patients with type2-diabetes will be recruited getting exclusively arm 8. They are the comparison group to the healthy and prediabetic volunteers.

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Brief Summary in Scientific Language

Bovine milk consists of 80% casein and 20% whey protein. Casein forms clots in an acidic environment or in the presence of the enzymes chymosin or pepsin. The formation of clots is suggested to delay gastric emptying which was shown in rats so far. In contrast, whey protein precipitates more disperse and thereby may be handled in the stomach more as a liquid diet. Glycomacropeptide (GMP) is a glycosylated peptide which inhibits gastrin and in turn the synthesis of gastric acid.
Human studies have displayed a strong potential of whey protein to elevate the insulin response and in turn to reduce glycemia. This effect is partly related to an induction of the incretin hormones glucose insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). However, the exact biochemical mechanism of whey protein to stimulate the incretin hormones and insulin secretion is unknown so far. Furthermore, whey protein is a superior protein in the promotion of satiety.
The aim of this study is to investigate the effects of the different milk fractions on gastric emptying and the metabolic response in humans. 15 Caucasian healthy and 15 prediabetic volunteers will be recruited.
The test drinks consist of either 50g whey protein isolate, 50g casein or 50g GMP and 50g maltodextrin19, 2g Hydroxyproline or 1g acetaminophen, 10g lactulose and aroma or of only 50g maltodextrin 19, 2g Hydroxyproline or 1g acetaminophen and 10g lactulose and aroma which is mixed with 300 ml room-tempered water.(healthy volunteers arms 1 to 4; prediabetic volunteers arms 5 to 8)
A venous line will be inserted in a forearm vein to collect blood after 0, 15, 30, 45, 60, 90, 120, 180 and 240 min and blood glucose will be analyzed immediately during the test phase. The feeling of hunger will be assessed by a visual analogue scale every hour. Lactulose is a non-absorbable ingredient and is fermented by bacteria in the colon whereby hydrogen is formed. To assess the transit time, hydrogen air will be measured in the exhalation air every half hour. Acetaminophen (marker for gastric emptying), GIP, GLP-1, insulin, C-peptide, glucagon, ghrelin, dipeptidylpeptidase IV, amino acids, acylcarnitines and phospholipids will be analyzed in the plasma. Cysteine is highly abundant in whey protein and necessary for the formation of glutathione. To assess if the different milk fractions influence the oxidative stress defense system, glutathione reductase, superoxiddismutase (SOD) and catalase will be analyzed in peripheral mononuclear cells at time points 0, 30 and 240 min.

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Do you plan to share individual participant data with other researchers?

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00005682
  •   2014/02/25
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  •   no
  •   Approved
  •   2436/09, Ethik-Kommission der Fakultät für Medizin der Technischen Universität München
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Secondary IDs

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Health Condition or Problem studied

  •   glucose homeostasis
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Interventions/Observational Groups

  •   Healthy volunteer
    50g whey protein
    50g maltodextrin19
    10g lactulose
    2g Hydroxyproline
    vanilla- or lemonflavour
    solved in 300ml water
  •   Healthy volunteer
    50g casein
    50g maltodextrin19
    10g lactulose
    2g Hydroxyproline
    vanilla- or lemonflavour
    solved in 300ml water
  •   Healthy volunteer
    50g maltodextrin19
    10g lactulose
    2g Hydroxyproline
    vanilla- or lemonflavour
    solved in 300ml water
  •   Healthy volunteer
    50g glycomacropeptide
    50g maltodextrin19
    10g lactulose
    1g acetaminophen
    vanilla- or lemonflavour
    solved in 300ml water
  •   Prediabetic volunteer
    50g glycomacropeptide
    50g maltodextrin19
    10g lactulose
    1g acetaminophen
    vanilla- or lemonflavour
    solved in 300ml water
  •   Prediabetic volunteer
    50g whey protein
    50g maltodextrin19
    10g lactulose
    1g acetaminophen
    vanilla- or lemonflavour
    solved in 300ml water
  •   Prediabetic volunteer
    50g casein
    50g maltodextrin19
    10g lactulose
    1g acetaminophen
    vanilla- or lemonflavour
    solved in 300ml water
  •   Prediabetic volunteer and type2-diabetic patient
    50g maltodextrin 19
    10g lactulose
    1g acetaminophen
    vanilla- or lemon flavour
    solved in 300ml water
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   patient/subject
  •   Active control (effective treament of control group)
  •   Basic research/physiological study
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

Hemocue: glucose
Multiplex: insulin,GIP, C-peptides, glucagon
Elisa: GLP-1

time span: up to 240 min after intake in the fasting state

reading points: 0, 15, 30, 45, 60, 90, 120, 180, and 240 min

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Secondary Outcome

LC-MS/MS: acetaminophen, amino acids, acylcarnitine
Multiplex: ghrelin
Spectrometer: superoxiddismutase, catalase, glutathionreductase, dipeptidylpeptidase IV, ß-hydroxybutyrate, non esterified free fatty acids
visual analogue scale feeling of hunger

time span: up to 240 min after intake in the fasting state

reading points: 0, 15, 30, 45, 60, 90, 120, 180, and 240 min
reading points for visual analogue scale: every 30 min
reading points forSOD, catalase, glutathione reductase: 0, 30, 240 min

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • other 
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Recruitment

  •   Actual
  •   2009/10/05
  •   45
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   20   Years
  •   74   Years
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Additional Inclusion Criteria

Inclusion criteria for healthy volunteers:
-age between 20 and 50 years -BMI 20 up to 28 kg/m2 -written consent

Inclusion criteria for prediabetic volunteers:
-age between 20 and 50 years -confirmation of the prediabetic state corresponding to the definition of the WHO. ( Glucose tolerance test: baseline/fasting state ≥ 6,1 mmol/l (≥ 110 mg/dl) and < 7,0 mmol/l (< 126 mg/dl) in venous plasma or ≥ 5,6 mmol/l (≥ 100 mg/dl) and < 6,0 mmol/l (< 109 mg/dl) in capillary whole blood and/or 2 hour sample ≥ 7,8 mmol/l (≥ 140 mg/dl) and <11,1 mmol/l (< 200 mg/dl) in venous plasma or capillary whole blood -written consent

Inclusion criteria for diabetic patients:
-age up to 74 years -single Metformin therapy -written consent

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Exclusion Criteria

Exclusion criteriy for healthy volunteers:
-chronic diseases e.g. diabetes mellitus, inflammatory diseases, cardiovaskular diseases, infectious diseases
-severe depression
-known drug- and alcoholabuse
-medication
-smoker

Exclusion criteria for prediabetic volunteers:
-chronic diseases e.g.iinflammatory diseases, cardiovaskular diseases, infectious diseases
-severe depression
-known drug- and alcoholabuse
-medication
-smoker

Exclusion criteria for diabetic patients:
-severe depression
-known drug- and alcoholabuse
-smoker

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Addresses

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    • Kraft Foods R&D Inc.Zweigniederlassung München
    • Bayerwaldstr. 8
    • 81737  München
    • Germany
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    • Wissenschaftszentrum WeihenstephanLehrstuhl für ErnährungsphysiologieTechnische Universität München
    • Ms.  Prof.Dr.  Hannelore  Daniel 
    • Gregor-Mendel-Strasse 2
    • 85350  Freising
    • Germany
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    • Wissenschaftszentrum WeihenstephanLehrstuhl für ErnährungsphysiologieTechnische Universität München
    • Ms.  Dipl.-Troph.  Anja  Höfle 
    • Gregor-Mendel-Strasse 2
    • 85350  Freising
    • Germany
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Sources of Monetary or Material Support

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    • Kraft Foods R&D Inc.Zweigniederlassung München
    • Bayerwaldstr. 8
    • 81737  München
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2014/08/27
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Trial Publications, Results and other Documents

  •   Hoefle AS; Bangert AM, Stamford A, Gedrich K, Rist MJ, Lee YM, Skurk T, Daniel H. J Nutr 2015 Mar;145(3):467-75
  •   Hoefle AS, Bangert AM, Rist MJ, Gedrich K, Lee YM, Skurk T, Danier J, Schwarzenbolz U, Daniel H. Postprandial metabolic responses to the ingestion of bovine glycomacropeptide compared to a whey protein isolate in prediabetic volunteers. Eur J Nutr. (2018) https://doi.org/10.1007/s00394-018-1763-5
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* This entry means the parameter is not applicable or has not been set.