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

Obesity Clinical Trial

Official title:

Vitamin K and Glucose Metabolism in Children at Risk for Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01972113
• Other study ID #: 611523 (Pro00000912)
• Secondary ID: 16GRNT31090037
• Status: Recruiting
• Phase: N/A
• Start date: September 2013
• Est. completion date: December 30, 2020

Study information

• Verified date: November 2019
• Source: Augusta University
• Contact: Norman K Pollock, Ph.D.
• Phone: 706-721-5424
• Email: npollock[@]augusta.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 30, 2020
• Est. primary completion date: August 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Dyslipidemia
• Dyslipidemias
• Glucose Intolerance
• Hypersensitivity
• Insulin Resistance
• Insulin Sensitivity
• Obesity
• Prediabetes
• Prediabetic State

Intervention

Dietary Supplement:
• Placebo-Control
one placebo softgel capsules per day (for 8 weeks) containing no vitamin K2 (menaquinone-7)
• 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
• High-Dose Vitamin K2 (menaquinone-7; 90 mcg/d)
one 90-mcg vitamin K2 (menaquinone-7) softgel capsules per day for 8 weeks

Locations

Country	Name	City	State
United States	Medical College of Georgia; Augusta University	Augusta	Georgia

Sponsors (4)

Lead Sponsor	Collaborator
Augusta University	Tufts University, University of Alabama at Birmingham, Yale University

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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 Aug 9. pii: jn253666. doi: 10.3945/jn.117.253666. [Epub ahead of print] — View Citation

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. — View Citation

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 ß-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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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