Clinical trial NCT01972113: Vitamin K and Glucose Metabolism in Children at Risk for Diabetes (Vita-K 'n' Kids Study)
Official title: Vitamin K and Glucose Metabolism in Children at Risk for Diabetes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity
Insulin Resistance
Insulin Sensitivity
Prediabetes
Dyslipidemia
Diabetes
Keywords: Vitamin K
Vitamin K2
Menaquinone-7
Osteocalcin
Children
Obesity
Insulin resistance
Insulin sensitivity
Beta-cell function
Prediabetes
Matrix Gla protein
Arterial stiffness
Endothelial function
Lead sponsor: Augusta University
Sponsor class: OTHER
Collaborators: name: University of Alabama at Birmingham
name: Yale University
name: Tufts University
First posted: 2013-10-30
Enrollment: 30
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility 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

Primary outcomes:
measure: Change in serum lipid concentrations
timeFrame: 8 weeks
measure: Change in insulin sensitivity
timeFrame: 8 weeks
measure: Change in beta-cell function
timeFrame: 8 weeks
Secondary outcomes:
measure: Change in coagulation
timeFrame: 8 weeks
measure: Change in arterial stiffness (pulse wave velocity)
timeFrame: 8 weeks
measure: Change in endothelial function (Flow-mediated dilation)
timeFrame: 8 weeks
measure: Effects of sex, race, bone age, and pubertal stage on changes in glucosemetabolism (insulin sensitivity and beta-cell function)
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Medical College of Georgia; Augusta University
state: Georgia
Study officials:
affiliation: Department of Medicine, Medical College of Georgia, Augusta University
name: Norman K Pollock, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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 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.
citation: 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.
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.
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 Oct 1;147(10):1960-1967. doi: 10.3945/jn.117.253666.
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.