Vitamin K to Slow Progression of Dyslipidemia and Diabetes Risk (Vita-K 'n' Kids Study II)

Study Overview
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Brief Summary
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Animal studies have found that vitamin K-dependent proteins matrix Gla protein and osteocalcin beneficially influence lipid and glucose metabolism, respectively. However, this concept has not been tested in humans at risk for dyslipidemia and diabetes risk. Vitamin K supplementation presents an opportunity to test the hypothesized link between the vitamin K-dependent proteins and markers of lipid and glucose metabolism. The investigators will conduct an 8-week vitamin K intervention (to manipulate carboxylation of matrix Gla protein and osteocalcin) and determine its effects on markers of dyslipidemia and diabetes risk. Sixty obese children will be randomly allocated to either the control group receiving placebo or the low-dose (45 mcg/d) or high-dose group (90 mcg/d) receiving vitamin K (menaquinone-7).

Official Title
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Vitamin K to Slow Progression of Dyslipidemia and Diabetes Risk

Conditions
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Obesity, Insulin Resistance, Obesity in Diabetes, Nutritional and Metabolic Diseases, Hyperlipidemia, Hyperglycemia, Cardiovascular Diseases

Intervention / Treatment
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* Dietary Supplement: Placebo-Control
* Dietary Supplement: Low-Dose Vitamin K2 (menaquinone-7; 45-mcg/d)
* Dietary Supplement: High-Dose Vitamin K2 (menaquinone-7; 90 mcg/d)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 8 to 17 years Body mass index equal to or greater than 85th percentile for age and sex Subject and parent/guardian understands the study protocol and agrees to comply with it Informed Consent Form signed by the parent/guardian and assent 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: 8 Years
Maximum Age: 17 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-Control<br>* two placebo softgel capsules per day (for 8 weeks) containing no vitamin K2 (menaquinone-7)<br>|
| Active Comparator: Low-Dose Vitamin K2 (45-mcg/d)<br>The low-dose vitamin K2 group will take one 45-mcg vitamin K2 softgel capsule and one placebo softgel capsule every day for 8 weeks. | Dietary Supplement: Low-Dose Vitamin K2 (menaquinone-7; 45-mcg/d)<br>* one 45-mcg vitamin K2 (menaquinone-7) softgel capsule per day and one placebo softgel per day (containing no menaquinone-7) for 8 weeks<br>* Other names: menaquinone-7;|
| Active Comparator: High-Dose Vitamin K2 (90-mcg/d)<br>The high-dose vitamin K2 group will take two 45-mcg vitamin K2 softgel capsules every day for 8 weeks. | Dietary Supplement: High-Dose Vitamin K2 (menaquinone-7; 90 mcg/d)<br>* two 45-mcg vitamin K2 (menaquinone-7) softgel capsules per day for 8 weeks<br>* Other names: menaquinone-7;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum lipid concentrations | To determine if the vitamin K-induced change in matrix Gla protein carboxylation improves fasting lipid panel (triglycerides, total cholesterol, HDL-cholesterol, and LDL-cholesterol) in a dose-dependent manner. | 8 weeks | 
| Change in insulin sensitivity | To determine if the vitamin K-induced change in osteocalcin carboxylation effects insulin sensitivity in a dose-dependent manner. Insulin sensitivity will be calculated from plasma insulin and glucose concentrations measured during a two-hour oral glucose tolerance test by using the oral glucose minimal model. | 8 weeks | 
| Change in beta-cell function | To determine if the vitamin K-induced change in osteocalcin carboxylation effects beta-cell function in a dose-dependent manner. Beta-cell function, as assessed by dynamic beta-cell responsitivity, will be calculated from plasma glucose and C-peptide concentrations measured during a two-hour oral glucose tolerance test by using the oral C-peptide minimal model. | 8-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in coagulation | Coagulation-related parameters (i.e., prothrombin time and activated partial thromboplastin time) will be assessed at baseline and 8 weeks to assess clotting function. | 8 weeks | 
| Change in arterial stiffness (pulse wave velocity) | Arterial stiffness, as measured by pulse wave velocity (PWV), will be assessed at baseline and 8 weeks to explore whether change in arterial stiffness is influenced by vitamin K2 supplementation. | 8 weeks | 
| Change in endothelial function (flow-mediated dilation) | Endothelial function, as measured by flow-mediated dilation (FMD), will be assessed at baseline and 8 weeks to explore whether change in endothelial function is influenced by vitamin K2 supplementation. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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G01 [Biological Sciences], G02.513 [Nutrition], G06.696.259 [Child Nutrition], G07.553.481.398.571 [Obesity], G06 [Biochemical Phenomena, Metabolism, and Nutrition], G12.392.617 [Insulin Resistance], G06.696.259.500 [Adolescent Nutrition], A06 [Endocrine System], A07 [Cardiovascular System], C18.452.297.681 [Obesity in Diabetes], C18.452.555 [Insulin Resistance], C18 [Nutritional and Metabolic Diseases], C18.452.494 [Hyperlipidemia], C18.452.460 [Hyperglycemia], C14 [Cardiovascular Diseases], D11.786.875.844 [Vitamin K 2], D02.806.550.750 [Vitamin K 2], E02.293 [Diet Therapy], E02 [Therapeutics], F04.096.544.215.508.428 [Primary Prevention], N01.224.425.525 [Nutritional Status]