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

Primary Purpose

Obesity, Insulin Resistance, Insulin Sensitivity

Status

Unknown status

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Placebo-Control

Low-Dose Vitamin K2 (menaquinone-7; 45 mcg/d)

High-Dose Vitamin K2 (menaquinone-7; 90 mcg/d)

About this trial

This is an interventional prevention trial for Obesity focused on measuring Vitamin K, Vitamin K2, Menaquinone-7, Osteocalcin, Children, Obesity, Insulin resistance, Insulin sensitivity, Beta-cell function, Prediabetes, Matrix Gla protein, Arterial stiffness, Endothelial function

Eligibility Criteria

8 Years - 17 Years (Child)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Medical College of Georgia; Augusta UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo-Control

Low-Dose Vitamin K2 (45 mcg/d)

High-Dose Vitamin K2 (90 mcg/d)

Arm Description

The placebo-control group will take one placebo softgel capsules every day for 8 weeks.

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.

The high-dose vitamin K2 group will take one 90-mcg vitamin K2 softgel capsules every day for 8 weeks.

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

Full Information

NCT ID

NCT01972113

First Posted

October 24, 2013

Last Updated

November 18, 2019

Sponsor

Augusta University

Collaborators

University of Alabama at Birmingham, Yale University, Tufts University

1. Study Identification

Unique Protocol Identification Number

NCT01972113

Brief Title

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

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Unknown status

Study Start Date

September 2013 (undefined)

Primary Completion Date

August 30, 2020 (Anticipated)

Study Completion Date

December 30, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Augusta University

Collaborators

University of Alabama at Birmingham, Yale University, Tufts University

4. Oversight

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Placebo-Control

Arm Type

Placebo Comparator

Arm Description

The placebo-control group will take one placebo softgel capsules every day for 8 weeks.

Arm Title

Low-Dose Vitamin K2 (45 mcg/d)

Arm Type

Active Comparator

Arm Description

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.

Arm Title

High-Dose Vitamin K2 (90 mcg/d)

Arm Type

Active Comparator

Arm Description

The high-dose vitamin K2 group will take one 90-mcg vitamin K2 softgel capsules every day for 8 weeks.

Intervention Type

Dietary Supplement

Intervention Name(s)

Placebo-Control

Intervention Description

one placebo softgel capsules per day (for 8 weeks) containing no vitamin K2 (menaquinone-7)

Intervention Type

Dietary Supplement

Intervention Name(s)

Low-Dose Vitamin K2 (menaquinone-7; 45 mcg/d)

Other Intervention Name(s)

menaquinone-7

Intervention Description

one 45-mcg vitamin K2 (menaquinone-7) softgel capsule per day and one placebo softgel per day (containing no menaquinone-7) for 8 weeks

Intervention Type

Dietary Supplement

Intervention Name(s)

High-Dose Vitamin K2 (menaquinone-7; 90 mcg/d)

Other Intervention Name(s)

menaquinone-7

Intervention Description

one 90-mcg vitamin K2 (menaquinone-7) softgel capsules per day for 8 weeks

Primary Outcome Measure Information:

Title

Change in serum lipid concentrations

Description

To determine if vitamin K supplementation improves fasting lipid panel (triglycerides, total cholesterol, HDL-cholesterol, and LDL-cholesterol) in a dose-dependent manner.

Time Frame

8 weeks

Title

Change in insulin sensitivity

Description

Time Frame

8 weeks

Title

Change in beta-cell function

Description

Time Frame

8 weeks

Secondary Outcome Measure Information:

Title

Change in coagulation

Description

Coagulation-related parameters (i.e., prothrombin time and activated partial thromboplastin time) will be assessed at baseline and 8 weeks to assess clotting function.

Time Frame

8 weeks

Title

Change in arterial stiffness (pulse wave velocity)

Description

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.

Time Frame

8 weeks

Title

Change in endothelial function (Flow-mediated dilation)

Description

Time Frame

8 weeks

Title

Effects of sex, race, bone age, and pubertal stage on changes in glucosemetabolism (insulin sensitivity and beta-cell function)

Description

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.

Time Frame

8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

8 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Norman K Pollock, Ph.D.

Phone

706-721-5424

npollock@augusta.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Celestine F Williams, M.S.

Phone

706-721-8553

cewilliams@augusta.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Norman K Pollock, Ph.D.

Organizational Affiliation

Department of Medicine, Medical College of Georgia, Augusta University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medical College of Georgia; Augusta University

City

Augusta

State/Province

Georgia

ZIP/Postal Code

30909

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Norman K Pollock, Ph.D.

12. IPD Sharing Statement

Citations:

PubMed Identifier

21508147

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.

Results Reference

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PubMed Identifier

23616149

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. Erratum In: J Clin Endocrinol Metab. 2016 May;101(5):2265.

Results Reference

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PubMed Identifier

23147574

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.

Results Reference

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PubMed Identifier

25817542

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.

Results Reference

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PubMed Identifier

28794209

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.

Results Reference

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PubMed Identifier

29635270

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.

Results Reference

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

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