NCT01972113

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
30

participants targeted

Target at below P25 for not_applicable obesity

Timeline
Completed

Started Sep 2013

Longer than P75 for not_applicable obesity

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2013

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

October 24, 2013

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 30, 2013

Completed
6.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 30, 2020

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 30, 2020

Completed
Last Updated

November 19, 2019

Status Verified

November 1, 2019

Enrollment Period

7 years

First QC Date

October 24, 2013

Last Update Submit

November 18, 2019

Conditions

Keywords

Vitamin KVitamin K2Menaquinone-7OsteocalcinChildrenObesityInsulin resistanceInsulin sensitivityBeta-cell functionPrediabetesMatrix Gla proteinArterial stiffnessEndothelial function

Outcome Measures

Primary Outcomes (3)

  • 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

Secondary Outcomes (4)

  • Change in coagulation

    8 weeks

  • Change in arterial stiffness (pulse wave velocity)

    8 weeks

  • Change in endothelial function (Flow-mediated dilation)

    8 weeks

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

    8 weeks

Study Arms (3)

Placebo-Control

PLACEBO COMPARATOR

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

Dietary Supplement: Placebo-Control

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.

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

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.

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

Interventions

Placebo-ControlDIETARY_SUPPLEMENT

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

Placebo-Control

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

Also known as: menaquinone-7
Low-Dose Vitamin K2 (45 mcg/d)

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

Also known as: menaquinone-7
High-Dose Vitamin K2 (90 mcg/d)

Eligibility Criteria

Age8 Years - 17 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Medical College of Georgia; Augusta University

Augusta, Georgia, 30909, United States

RECRUITING

Related Publications (6)

  • 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.

    PMID: 21508147BACKGROUND
  • 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.

    PMID: 23616149BACKGROUND
  • 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.

    PMID: 23147574BACKGROUND
  • 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.

    PMID: 25817542BACKGROUND
  • 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.

    PMID: 28794209BACKGROUND
  • 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.

    PMID: 29635270BACKGROUND

MeSH Terms

Conditions

ObesityInsulin ResistancePrediabetic StateDyslipidemiasDiabetes Mellitus

Interventions

Vitamin K 2menaquinone 7

Condition Hierarchy (Ancestors)

OverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesEndocrine System DiseasesLipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Vitamin KNaphthoquinonesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPhytolDiterpenesTerpenesQuinonesPolycyclic Compounds

Study Officials

  • Norman K Pollock, Ph.D.

    Department of Medicine, Medical College of Georgia, Augusta University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Norman K Pollock, Ph.D.

CONTACT

Celestine F Williams, M.S.

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor, Department of Medicine

Study Record Dates

First Submitted

October 24, 2013

First Posted

October 30, 2013

Study Start

September 1, 2013

Primary Completion

August 30, 2020

Study Completion

December 30, 2020

Last Updated

November 19, 2019

Record last verified: 2019-11

Locations