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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2016 by Georgia Regents University
Sponsor:
Collaborators:
University of Alabama at Birmingham
Yale University
Tufts University
NattoPharma, ASA
Information provided by (Responsible Party):
Norman Pollock, Georgia Regents University
ClinicalTrials.gov Identifier:
NCT01972113
First received: October 24, 2013
Last updated: June 23, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Obesity
Insulin Resistance
Insulin Sensitivity
Prediabetes
Dyslipidemia
Diabetes
Dietary Supplement: Placebo-Control
Dietary Supplement: Low-Dose Vitamin K2 (menaquinone-7; 45 mcg/d)
Dietary Supplement: High-Dose Vitamin K2 (menaquinone-7; 90 mcg/d)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Vitamin K and Glucose Metabolism in Children at Risk for Diabetes

Resource links provided by NLM:


Further study details as provided by Georgia Regents University:

Primary Outcome Measures:
  • Change in insulin sensitivity [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    The first primary aim is to determine if the vitamin K-induced changes in carboxylation of osteocalcin and matrix Gla protein effects insulin sensitivity in a dose-dependent manner. Insulin sensitivity will be calculated from plasma insulin and glucose concentrations measured during a two-hour oral glucose tolerance test by using the oral glucose minimal model.

  • Change in beta-cell function [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    The second primary aim is to determine if the vitamin K-induced changes in carboxylation of osteocalcin and matrix Gla protein effects beta-cell function 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 two-hour oral glucose tolerance test by using the oral C-peptide minimal model.


Secondary Outcome Measures:
  • Change in coagulation [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Coagulation-related parameters (i.e., prothrombin time and activated partial thromboplastin time) will be assessed at baseline and 8 weeks to assess clotting function.

  • Changes in serum adipokine concentrations [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Adipokines leptin and adiponectin will be measured in fasting serum at baseline and 8 weeks to explore whether changes in serum adipokine concentrations are influenced by vitamin K2 supplementation.

  • Change in arterial stiffness (pulse wave velocity) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Changes in serum lipid concentrations [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Fasting lipid panel (triglycerides, total cholesterol, HDL-cholesterol, non-HDL-cholesterol, LDL-cholesterol) will be taken at baseline and 8 weeks to explore whether changes in serum lipid are influenced by vitamin K2 supplementation.

  • Effects of sex, race, bone age, and pubertal stage on changes in glucosemetabolism (insulin sensitivity and beta-cell function) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 60
Study Start Date: September 2013
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo-Control
The placebo-control group will take two placebo softgel capsules every day for 8 weeks.
Dietary Supplement: Placebo-Control
two placebo softgel capsules per day (for 8 weeks) containing no vitamin K2 (menaquinone-7)
Active Comparator: Low-Dose Vitamin K2 (45 mcg/d)
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)
one 45-mcg vitamin K2 (menaquinone-7) softgel capsule per day and one placebo softgel per day (containing no menaquinone-7) for 8 weeks
Other Name: menaquinone-7
Active Comparator: High-Dose Vitamin K2 (90 mcg/d)
The high-dose vitamin K2 group will take two 45-mcg vitamin K2 softgel capsules every day for 8 weeks.
Dietary Supplement: High-Dose Vitamin K2 (menaquinone-7; 90 mcg/d)
two 45-mcg vitamin K2 (menaquinone-7) softgel capsules per day for 8 weeks
Other Name: menaquinone-7

  Eligibility

Ages Eligible for Study:   8 Years to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 8 to 17 years
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01972113

Contacts
Contact: Norman K Pollock, Ph.D. 706-721-5424 npollock@gru.edu

Locations
United States, Georgia
Medical College of Georgia; Georgia Regents University Recruiting
Augusta, Georgia, United States, 30909
Principal Investigator: Norman K Pollock, Ph.D.         
Sponsors and Collaborators
Georgia Regents University
University of Alabama at Birmingham
Yale University
Tufts University
NattoPharma, ASA
Investigators
Principal Investigator: Norman K Pollock, Ph.D. Department of Pediatrics, Medical College of Georgia, Georgia Regents University
  More Information

Publications:
Responsible Party: Norman Pollock, Associate Professor, Department of Pediatrics, Georgia Regents University
ClinicalTrials.gov Identifier: NCT01972113     History of Changes
Other Study ID Numbers: 611523 (Pro00000912) 
Study First Received: October 24, 2013
Last Updated: June 23, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Georgia Regents University:
Insulin resistance
Insulin sensitivity
Vitamin K
Vitamin K2
Menaquinone-7
Osteocalcin
Children
Obesity
Beta-cell function
Prediabetes
Matrix Gla protein
Arterial stiffness
Endothelial function

Additional relevant MeSH terms:
Insulin Resistance
Diabetes Mellitus
Hypersensitivity
Dyslipidemias
Prediabetic State
Glucose Intolerance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperinsulinism
Immune System Diseases
Lipid Metabolism Disorders
Hyperglycemia
Vitamins
Vitamin K
Vitamin K 2
Vitamin MK 7
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants

ClinicalTrials.gov processed this record on July 21, 2016