Vitamin K and Glucose Metabolism in Adults at Risk for Diabetes (Vita-K 'n' Adults Study)

Study Overview
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Brief Summary
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Given that glutamate carboxylation or decarboxylation is key to the metabolic role of osteocalcin (at least in mouse models) and that carboxylation is vitamin K dependent, it is critical to isolate the effect of vitamin K manipulation on carboxylation of osteocalcin and its subsequent effect on glucose metabolism in clinical trials. The purpose of this randomized, double-blind, placebo-controlled clinical trial in adults is to determine whether eight weeks of daily supplementation with vitamin K2 (menaquinone-7) can improve markers in blood associated with diabetes risk.

Official Title
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Vitamin K and Glucose Metabolism in Adults at Risk for Diabetes

Conditions
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Obesity, Insulin Resistance, Insulin Sensitivity, Beta-Cell Dysfunction, Prediabetes

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: Low-Dose Vitamin K2 Supplement (menaquinone-7; 90-mcg/d)
* Dietary Supplement: High-Dose Vitamin K2 Supplement (menaquinone-7; 180-mcg/d)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults between 18 and 65 years old Subject understands the study protocol and agrees to comply with it Informed Consent Form signed by the subject Exclusion Criteria: Subjects using vitamin supplements containing vitamin k Subjects with (a history of) metabolic or gastrointestinal diseases including hepatic disorders Subjects presenting chronic degenerative and/or inflammatory diseases Subjects receiving systemic treatment or topical treatment likely to interfere with evaluation of the study parameters (salicylates, antibiotics) Subjects receiving corticosteroid treatment Subjects using oral anticoagulants Subjects with a history of soy allergy Subjects who have participated in a clinical study more recently than one month before the current study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo-Control<br>The placebo-control group will take two placebo softgel capsules every day for 8 weeks. | Dietary Supplement: Placebo<br>* Two placebo softgel capsules (containing no vitamin K2) every day for 8 weeks.<br>|
| Active Comparator: Low-Dose Vitamin K2 (90-mcg/d)<br>The low-dose vitamin K group will take one 90-mcg vitamin K2 (menaquinone-7) softgel capsule and one placebo softgel capsule every day for 8 weeks. | Dietary Supplement: Low-Dose Vitamin K2 Supplement (menaquinone-7; 90-mcg/d)<br>* One 90-mcg vitamin K2 softgel capsules (containing no vitamin K2) and one placebo softgel capsule everyday for 8 weeks.<br>|
| Active Comparator: High-Dose Vitamin K2 (180-mcg/d)<br>The high-dose vitamin K group will take two 90-mcg vitamin K2 (menaquinone-7) softgel capsules every day for 8 weeks. | Dietary Supplement: High-Dose Vitamin K2 Supplement (menaquinone-7; 180-mcg/d)<br>* Two 90-mcg vitamin K2 softgel capsules every day for 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in insulin sensitivity | Insulin sensitivity will be calculated from plasma insulin and glucose concentrations measured during a 2-hour oral glucose tolerance test by using the oral glucose minimal model. | Change from baseline in insulin sensitivity at 8 weeks | 
| Change in beta-cell function | Beta-cell function, as assessed by dynamic beta-cell responsitivity, will be calculated from plasma glucose and C-peptide concentrations measured during a 2-hour oral glucose tolerance test by using the oral C-peptide minimal model. | Change from baseline in beta-cell function at 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in prothrombin time (PT) |  | Change from baseline in PT at 8 weeks | 
| Change in activated partial thromboplastin time (aPTT) |  | Change from baseline in aPTT at 8 weeks | 
| Change in arterial stiffness (PWV) | Arterial stiffness will be assessed using carotid-femoral pulse wave velocity (PWV) by applanation tonometry. | Change from baseline in arterial stiffness at 8 weeks | 
| Change in endothelial function (FMD) | Endothelial function will be assessed using brachial artery flow-mediated dilation (FMD) by ultrasound. | Change from baseline in endothelial function at 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin K, Vitamin K2, Menaquinone-7, Osteocalcin, Adults, Obesity, Insulin resistance, Insulin sensitivity, Beta-cell function, Prediabetes