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

• ClinicalTrials.gov Identifier: NCT01972113
• Recruitment Status: Unknown
• First Posted: October 30, 2013
• Last Update Posted: November 19, 2019
• Sponsor: Augusta University
• Collaborators: University of Alabama at Birmingham; Yale University; Tufts University
• Information provided by (Responsible Party): Norman Pollock, Augusta University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Obesity; Insulin Resistance; Insulin Sensitivity; Prediabetes; Dyslipidemia; Diabetes	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)	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Vitamin K and Glucose Metabolism in Children at Risk for Diabetes
• Study Start Date: September 2013
• Estimated Primary Completion Date: August 30, 2020
• Estimated Study Completion Date: December 30, 2020

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo-Control; The placebo-control group will take one placebo softgel capsules every day for 8 weeks.	Dietary Supplement: Placebo-Control; one placebo softgel capsules per day (for 8 weeks) containing no vitamin K2 (menaquinone-7)
Active Comparator: Low-Dose Vitamin K2 (45 mcg/d); 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); one 45-mcg vitamin K2 (menaquinone-7) softgel capsule per day and one placebo softgel per day (containing no menaquinone-7) for 8 weeks; Other Name: menaquinone-7
Active Comparator: High-Dose Vitamin K2 (90 mcg/d); 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); one 90-mcg vitamin K2 (menaquinone-7) softgel capsules per day for 8 weeks; Other Name: menaquinone-7

Outcome Measures

Primary Outcome Measures :

1. Change in serum lipid concentrations [ Time Frame: 8 weeks ]
   To determine if vitamin K supplementation improves fasting lipid panel (triglycerides, total cholesterol, HDL-cholesterol, and LDL-cholesterol) in a dose-dependent manner.
2. Change in insulin sensitivity [ Time Frame: 8 weeks ]
   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.
3. Change in beta-cell function [ Time Frame: 8 weeks ]
   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.

Secondary Outcome Measures :

1. Change in coagulation [ Time Frame: 8 weeks ]
   Coagulation-related parameters (i.e., prothrombin time and activated partial thromboplastin time) will be assessed at baseline and 8 weeks to assess clotting function.
2. Change in arterial stiffness (pulse wave velocity) [ Time Frame: 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.
3. Change in endothelial function (Flow-mediated dilation) [ Time Frame: 8 weeks ]
   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.
4. Effects of sex, race, bone age, and pubertal stage on changes in glucosemetabolism (insulin sensitivity and beta-cell function) [ Time Frame: 8 weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 8 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Contacts

Contact: Norman K Pollock, Ph.D.; 706-721-5424; npollock@augusta.edu

Contact: Celestine F Williams, M.S.; 706-721-8553; cewilliams@augusta.edu

Locations

United States, Georgia

Medical College of Georgia; Augusta University; Recruiting

Augusta, Georgia, United States, 30909

Principal Investigator: Norman K Pollock, Ph.D.

Sponsors and Collaborators

Augusta University

University of Alabama at Birmingham

Yale University

Tufts University

Investigators

• Principal Investigator: Norman K Pollock, Ph.D.; Department of Medicine, Medical College of Georgia, Augusta University

More Information

Publications:

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.

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 β-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. Erratum in: J Clin Endocrinol Metab. 2016 May;101(5):2265.

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. Review.

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. Review.

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.

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.

• Responsible Party: Norman Pollock, Associate Professor, Department of Medicine, Augusta University
• ClinicalTrials.gov Identifier: NCT01972113
• Other Study ID Numbers: 611523 (Pro00000912); 16GRNT31090037 ( Other Grant/Funding Number: American Heart Association )
• First Posted: October 30, 2013
• Last Update Posted: November 19, 2019
• Last Verified: November 2019

Keywords provided by Norman Pollock, Augusta University:

Vitamin K; Vitamin K2; Menaquinone-7; Osteocalcin; Children; Obesity; Insulin resistance; Insulin sensitivity; Beta-cell function; Prediabetes; Matrix Gla protein; Arterial stiffness; Endothelial function

Additional relevant MeSH terms:

Diabetes Mellitus; Insulin Resistance; Dyslipidemias; Prediabetic State; Glucose Intolerance; Hypersensitivity; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Immune System Diseases; Hyperinsulinism; Lipid Metabolism Disorders; Hyperglycemia; Vitamins; Vitamin K; Vitamin K 2; Vitamin MK 7; Micronutrients; Physiological Effects of Drugs; Antifibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Hemostatics; Coagulants