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| ID | Type | Description | Link |
|---|---|---|---|
| 16GRNT31090037 | Other Grant/Funding Number | American Heart Association |
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| Name | Class |
|---|---|
| University of Alabama at Birmingham | OTHER |
| Yale University | OTHER |
| Tufts University | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo-Control | Placebo Comparator | The placebo-control group will take one placebo softgel capsules every day for 8 weeks. |
|
| Low-Dose Vitamin K2 (45 mcg/d) | Active Comparator | 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. |
|
| High-Dose Vitamin K2 (90 mcg/d) | Active Comparator | The high-dose vitamin K2 group will take one 90-mcg vitamin K2 softgel capsules every day for 8 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo-Control | Dietary Supplement | one placebo softgel capsules per day (for 8 weeks) containing no vitamin K2 (menaquinone-7) |
|
| 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 |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Norman K Pollock, Ph.D. | Contact | 706-721-5424 | npollock@augusta.edu | |
| Celestine F Williams, M.S. | Contact | 706-721-8553 | cewilliams@augusta.edu |
| Name | Affiliation | Role |
|---|---|---|
| Norman K Pollock, Ph.D. | Department of Medicine, Medical College of Georgia, Augusta University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical College of Georgia; Augusta University | Recruiting | Augusta | Georgia | 30909 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21508147 | Background | Pollock NK, Bernard PJ, Gower BA, Gundberg CM, Wenger K, Misra S, Bassali RW, Davis CL. Lower uncarboxylated osteocalcin concentrations in children with prediabetes is associated with beta-cell function. J Clin Endocrinol Metab. 2011 Jul;96(7):E1092-9. doi: 10.1210/jc.2010-2731. Epub 2011 Apr 20. | |
| 23616149 | Background |
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| Low-Dose Vitamin K2 (menaquinone-7; 45 mcg/d) | Dietary Supplement | one 45-mcg vitamin K2 (menaquinone-7) softgel capsule per day and one placebo softgel per day (containing no menaquinone-7) for 8 weeks |
|
|
| High-Dose Vitamin K2 (menaquinone-7; 90 mcg/d) | Dietary Supplement | one 90-mcg vitamin K2 (menaquinone-7) softgel capsules per day for 8 weeks |
|
|
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 |
| Gower BA, Pollock NK, Casazza K, Clemens TL, Goree LL, Granger WM. Associations of total and undercarboxylated osteocalcin with peripheral and hepatic insulin sensitivity and beta-cell function in overweight adults. J Clin Endocrinol Metab. 2013 Jul;98(7):E1173-80. doi: 10.1210/jc.2013-1203. Epub 2013 Apr 24. |
| 23147574 | Background | Booth SL, Centi A, Smith SR, Gundberg C. The role of osteocalcin in human glucose metabolism: marker or mediator? Nat Rev Endocrinol. 2013 Jan;9(1):43-55. doi: 10.1038/nrendo.2012.201. Epub 2012 Nov 13. |
| 25817542 | Background | Pollock NK. Childhood obesity, bone development, and cardiometabolic risk factors. Mol Cell Endocrinol. 2015 Jul 15;410:52-63. doi: 10.1016/j.mce.2015.03.016. Epub 2015 Mar 27. |
| 28794209 | Background | Douthit MK, Fain ME, Nguyen JT, Williams CF, Jasti AH, Gutin B, Pollock NK. Phylloquinone Intake Is Associated with Cardiac Structure and Function in Adolescents. J Nutr. 2017 Oct 1;147(10):1960-1967. doi: 10.3945/jn.117.253666. |
| 29635270 | Background | Fain ME, Kapuku GK, Paulson WD, Williams CF, Raed A, Dong Y, Knapen MHJ, Vermeer C, Pollock NK. Inactive Matrix Gla Protein, Arterial Stiffness, and Endothelial Function in African American Hemodialysis Patients. Am J Hypertens. 2018 May 7;31(6):735-741. doi: 10.1093/ajh/hpy049. |
| ID | Term |
|---|---|
| D009765 | Obesity |
| D007333 | Insulin Resistance |
| D011236 | Prediabetic State |
| D050171 | Dyslipidemias |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D052439 | Lipid Metabolism Disorders |
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| ID | Term |
|---|---|
| D024482 | Vitamin K 2 |
| C062629 | menaquinone 7 |
| ID | Term |
|---|---|
| D014812 | Vitamin K |
| D009285 | Naphthoquinones |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010836 | Phytol |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D011809 | Quinones |
| D011083 | Polycyclic Compounds |
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