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

Study Overview
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Brief Summary
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The undercarboxylated fractions of the two vitamin K-dependent proteins osteocalcin and matrix Gla protein have been shown to play key roles in type 2 diabetes and cardiovascular disease (at least in mouse models). Clinical trials are needed to isolate the effects of vitamin K manipulation on carboxylation of these two proteins (osteocalcin and matrix GLA protein) and their subsequent effects on markers of diabetes and cardiovascular disease risk. The purpose of this pilot randomized, double-blind, placebo-controlled trial in children is to estimate the effective dose of vitamin K2 (menaquinone-7) supplementation (to improve carboxylation of both osteocalcin and matrix Gla protein), and whether it can have an effect on markers associated with diabetes and cardiovascular disease risk.

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

Conditions
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Obesity, Insulin Resistance, Insulin Sensitivity, Prediabetes, Dyslipidemia, Diabetes

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 BMI less than 85th percentile for age and gender 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 one placebo softgel capsules every day for 8 weeks. | Dietary Supplement: Placebo-Control<br>* one 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 one 90-mcg vitamin K2 softgel capsules every day for 8 weeks. | Dietary Supplement: High-Dose Vitamin K2 (menaquinone-7; 90 mcg/d)<br>* one 90-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 vitamin K supplementation 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 vitamin K supplementation improves insulin sensitivity in a dose-dependent manner. Insulin sensitivity will be calculated from plasma insulin and glucose concentrations measured during a 2-hour glucose tolerance test by using the oral glucose minimal model. | 8 weeks | 
| Change in beta-cell function | To determine if vitamin K supplementation improves insulin sensitivity 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 2-hour 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 | 
| Effects of sex, race, bone age, and pubertal stage on changes in glucosemetabolism (insulin sensitivity and beta-cell function) | Moderation effects of sex, race, bone age, and pubertal stage in the associations of vitamin K-induced changes in carboxylation of osteocalcin on markers of glucose metabolism will be determined. | 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, Children, Obesity, Insulin resistance, Insulin sensitivity, Beta-cell function, Prediabetes, Matrix Gla protein, Arterial stiffness, Endothelial function