NCT02366481

Brief Summary

Given that glutamate carboxylation or decarboxylation is key to the metabolic role of osteocalcin (at least in mouse models) and that carboxylation is vitamin K dependent, it is critical to isolate the effect of vitamin K manipulation on carboxylation of osteocalcin and its subsequent effect on glucose metabolism in clinical trials. The purpose of this randomized, double-blind, placebo-controlled clinical trial in adults is to determine whether eight weeks of daily supplementation with vitamin K2 (menaquinone-7) can improve markers in blood associated with diabetes 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 Feb 2015

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

February 1, 2015

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

February 12, 2015

Completed
7 days until next milestone

First Posted

Study publicly available on registry

February 19, 2015

Completed
5.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2020

Completed
29 days until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2020

Completed
Last Updated

November 20, 2019

Status Verified

November 1, 2019

Enrollment Period

5.3 years

First QC Date

February 12, 2015

Last Update Submit

November 18, 2019

Conditions

ObesityInsulin ResistanceInsulin SensitivityBeta-Cell DysfunctionPrediabetes

Keywords

Vitamin KVitamin K2Menaquinone-7OsteocalcinAdultsObesityInsulin resistanceInsulin sensitivityBeta-cell functionPrediabetes

Outcome Measures

Primary Outcomes (2)

  • Change in insulin sensitivity

    Insulin sensitivity will be calculated from plasma insulin and glucose concentrations measured during a 2-hour oral glucose tolerance test by using the oral glucose minimal model.

    Change from baseline in insulin sensitivity at 8 weeks

  • Change in beta-cell function

    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 oral glucose tolerance test by using the oral C-peptide minimal model.

    Change from baseline in beta-cell function at 8 weeks

Secondary Outcomes (4)

  • Change in prothrombin time (PT)

    Change from baseline in PT at 8 weeks

  • Change in activated partial thromboplastin time (aPTT)

    Change from baseline in aPTT at 8 weeks

  • Change in arterial stiffness (PWV)

    Change from baseline in arterial stiffness at 8 weeks

  • Change in endothelial function (FMD)

    Change from baseline in endothelial function at 8 weeks

Study Arms (3)

Placebo-Control

PLACEBO COMPARATOR

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

Dietary Supplement: Placebo

Low-Dose Vitamin K2 (90-mcg/d)

ACTIVE COMPARATOR

The low-dose vitamin K group will take one 90-mcg vitamin K2 (menaquinone-7) softgel capsule and one placebo softgel capsule every day for 8 weeks.

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

High-Dose Vitamin K2 (180-mcg/d)

ACTIVE COMPARATOR

The high-dose vitamin K group will take two 90-mcg vitamin K2 (menaquinone-7) softgel capsules every day for 8 weeks.

Dietary Supplement: High-Dose Vitamin K2 Supplement (menaquinone-7; 180-mcg/d)

Interventions

PlaceboDIETARY_SUPPLEMENT

Two placebo softgel capsules (containing no vitamin K2) every day for 8 weeks.

Placebo-Control
Low-Dose Vitamin K2 Supplement (menaquinone-7; 90-mcg/d)DIETARY_SUPPLEMENT

One 90-mcg vitamin K2 softgel capsules (containing no vitamin K2) and one placebo softgel capsule everyday for 8 weeks.

Low-Dose Vitamin K2 (90-mcg/d)
High-Dose Vitamin K2 Supplement (menaquinone-7; 180-mcg/d)DIETARY_SUPPLEMENT

Two 90-mcg vitamin K2 softgel capsules every day for 8 weeks.

High-Dose Vitamin K2 (180-mcg/d)

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Healthy adults between 18 and 65 years old
  • Subject understands the study protocol and agrees to comply with it
  • Informed Consent Form 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, 30912, United States

Location

Related Publications (4)

  • 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

MeSH Terms

Conditions

ObesityInsulin ResistancePrediabetic State

Interventions

menaquinone 7

Condition Hierarchy (Ancestors)

OverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesDiabetes MellitusEndocrine System Diseases

Study Officials

  • Norman K Pollock, Ph.D.

    Department of Pediatrics, Medical College of Georgia, Augusta University

    PRINCIPAL INVESTIGATOR

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

February 12, 2015

First Posted

February 19, 2015

Study Start

February 1, 2015

Primary Completion

June 1, 2020

Study Completion

June 30, 2020

Last Updated

November 20, 2019

Record last verified: 2019-11

Locations

US(1)