Effects of 10-gram Collagen Protein Hydrolysate on Cardiometabolic Health

Study Overview
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Brief Summary
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The effects of a 10g/day collagen hydrolysate for a period of 4 weeks on glycemic control and cardiovascular health in a parallel design study using overweight/ obese men and women who are likely to have a disturbed lipid and glucose metabolism and increased risk to develop cardiovascular disease and/or Type- 2 diabetes.

Detailed Description
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Food-derived bioactive peptides represent a source of health-enhancing components that have been reported to have cardiovascular health benefits in humans and may be incorporated in functional foods. Up till now studies using collagen hydrolysates particularly addressed issues around joint health, however, there are some preliminary indications that other health-related targets might be affected as well. We here propose to focus on the potential effects of collagen hydrolysates on glycemic control, and characteristics of the microcirculation, both important parameters for the assessment of future cardiovascular disease (CVD) risk.

Official Title
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Effects of 10-gram Collagen Protein Hydrolysate on Cardiometabolic Health in Obese (BMI 25-35 kg/m2) Men and Women With Elevated Risk to Develop Type-2 Diabetes and CVD

Conditions
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Glucose Metabolism, Lipid Metabolism

Intervention / Treatment
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* Dietary Supplement: 10 g of collagen hydrolysate
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 40-75 years Men and women (in a ratio of 40/60 to 60/40) BMI between 25-35 kg/m2 Serum total cholesterol < 8.0 mmol/L (further testing is recommended for excessive hyperlipidemia [serum total cholesterol ≥ 8.0 mmol/L] according to the Standard for cardiovascular risk management of the Dutch general practitioner's community [Nederlands Huisartsen Genootschap]) Serum triacylglycerol < 4.5 mmol/L No current smoker No diabetic patients No familial hypercholesterolemia No abuse of drugs Not more than 4 alcoholic consumption per day with a maximum of 21 per week?? Stable body weight (weight gain or loss < 3 kg in the past three months) No use of medication known to treat blood pressure, lipid or glucose metabolism No use of an investigational product within another biomedical intervention trial within the previous 1-month No severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, autoinflammatory diseases, and rheumatoid arthritis No active cardiovascular disease like congestive heart failure or cardiovascular events, such as an acute myocardial infarction or cerebrovascular accident Willingness to give up being a blood donor from 8 weeks before the start of the study, during the study, and for 4 weeks after completion of the study No difficult venipuncture as evidenced during the screening visit Willing to comply to study protocol during the study Agree to take porcine / animal-derived supplements (i.e. collagen) Informed consent signed Exclusion Criteria: Allergy or intolerance to collagen or collagen hydrolysates Serum total cholesterol ≥ 8.0 mmol/L Serum triacylglycerol ≥ 4.5 mmol/L Current smoker, or smoking cessation <12 months Diabetic patients Familial hypercholesterolemia Abuse of drugs More than 4 alcoholic consumptions per day or 21 per week Unstable body weight (weight gain or loss > 3 kg in the past three months) Use medication known to treat blood pressure, lipid, or glucose metabolism Use of an investigational product within another biomedical intervention trial within the previous 1-month Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, autoinflammatory diseases, and rheumatoid arthritis Active cardiovascular diseases like congestive heart failure or cardiovascular events, such as an acute myocardial infarction or cerebrovascular accident Not willing to give up being a blood donor from 8 weeks before the start of the study, during the study, or for 4 weeks after completion of the study Not or difficult to venipuncture as evidenced during the screening visit Use of over-the-counter and prescribed medication or supplements, which may interfere with study measurements to be judged by the principal investigator; Use of oral antibiotics in 40 days or less prior to the start of the study; Blood donation in the past 3 months before the start of the study

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Parallel Assignment
Interventional Model Description: A 4-weeks randomized, controlled trial with a parallel design. Before the 4-weeks intervention, there is a 2-weeks run period.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Collagen hydrolysate<br>30 subjects will consume the protein hydrolysate daily for 4 weeks | Dietary Supplement: 10 g of collagen hydrolysate<br>* Before breakfast, participants consume 1 sachet every day for 4 weeks. The sachet contains 10-gram collagen protein hydrolysates + 5-gram erythritol and it has to be dissolved in 250 ml of water.<br>|
| Placebo Comparator: Placebo<br>30 subjects will consume the placebo daily for 4 weeks | Dietary Supplement: Placebo<br>* Before breakfast, participants consume 1 sachet every day for 4 weeks. The sachet contains 5-gram erythritol (placebo) and has to be dissolved in 250 ml of water.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic glucose metabolism | Measured by change in average daily glucose concentrations over a 15 hours period between waking up and going to bed 7:00-22:00 for three days, which is calculated based on the total area under the curve (tAUC) using a continuous glucose monitor. | pre- intervention and during the fourth week of intervention. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lipid metabolism | Measured by fasting serum, lipids and lipoproteins in all visits | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 1,2 and 3), and during the fourth week of intervention (visit 4, and 5) | 
| Glucose metabolism | Measured by fasting plasma glucose, and insulin in all visits | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 1,2 and 3), and during the fourth week of intervention (visit 4, and 5) | 
| Low-grade inflammation | Measured by inflammation plasma markers (Interleukin-6, Interleukin-8) | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 1,2 and 3), and during the fourth week of intervention (visit 4, and 5) | 
| Postprandial glucose metabolism | Following a high-fat, high-carb meal, measured by plasma glucose, insulin. | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 3), and immediately after the intervention (visit 5) | 
| Postprandial triacylglyceride metabolism | Following a high-fat, high-carb meal, measured by plasma triacylglyceride. | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 3), and immediately after the intervention (visit 5) | 
| Quality of life questionnaire | Assessed with a 32-item questionnaire (including social, spiritual, emotional, cognitive, physical, activities of daily living, and integrated quality of life) Outcome Measures 1-5 (1= Bad, 2=Below Average, 3= Average, 4=Above Average, 5=Good . | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 3), during (at home), and immediately after the intervention (visit 5) | 
| Mood, degree of pleasantness and arousal | Assessed with the Affect grid | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 3), during (at home), and immediately after the intervention (visit 5) | 
| Perceived Stress Scale | Assessed using the Perceived Stress Scale Scale, a 10-item questionnaire that is used to determine individual stress levels experienced in the past weeks during daily activities. Scores ranging from 0-40 Scores ranging from 0-13 would be considered low stress. Scores ranging from 14-26 would be considered moderate stress. Scores ranging from 27-40 would be considered high perceived stress. | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 3), during (at home), and immediately after the intervention (visit 5) | 
| Cognitive performance | Assessed with a validated neuropsychological test battery (Cambridge Neuropsychological Test Automated Battery) subjects will perform a neuropsychological test battery containing the anti-cue task (impulse control), the psychomotor vigilance test (sustained attention), the Attention Network Test, the N-Back task (working), the Rey Auditory Verbal Learning Task) (episodic memory), and the Trail Making Test (executive functioning). | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 3), and immediately after the intervention (visit 5) | 
| Venular and arteriolar diameters | Assessed via fundus photography | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 3), and immediately after the intervention (visit 5) | 
| Office blood pressure | Systolic and diastolic blood pressure measured by office blood pressure monitor in all visits | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 1,2 and 3), and during the fourth week of intervention (visit 4, and 5) | 
| 36-hours blood pressure profiles | Systolic and diastolic blood pressure assessed via wearable blood pressure monitor | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 3), and during the fourth week of intervention (visit 5) | 
| Sleep Quality | Assessed using the Pittsburgh Sleep Quality Index (PSQI) Consisting of 19 items. Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by A total of seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality. | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 3), during (at home), and immediately after the intervention (visit 5) | 
| Tumor necrosis factor alfa | Measured by inflammation plasma markers Tumor necrosis factor alfa | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 1,2 and 3), and during the fourth week of intervention (visit 4, and 5) | 
| C-reactive Protein | Measured by inflammation plasma markers C-reactive Protein | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 1,2 and 3), and during the fourth week of intervention (visit 4, and 5) | 
| Chronic glucose metabolism | Measured by fasting plasma glycated hemoglobin A1c | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 1,2 and 3), and during the fourth week of intervention (visit 4, and 5) | 
| Insulin sensitivity | Measured by fasting calculated homeostasis model assessment of insulin resistance in all visits | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 1,2 and 3), and during the fourth week of intervention (visit 4, and 5) | 
| C-peptide | Measured by fasting serum C-peptide | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 1,2 and 3), and during the fourth week of intervention (visit 4, and 5) | 
| Cerebral blood flow (CBF) | Measured using a DWL Multi-Dop T digital device (Compumedics Germany GmbH, Singen, Germany) | 2 weeks pre-intervention + 4 weeks intervention: Pre-intervention (visit 3), and immediately after the intervention (visit 5) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Collagen hydrolysate, Glucose metabolism, Dietary patterns, Cardiometabolic health