Effect of Vitamin K Supplementation on Markers of Diabetes Risk in Obese Children

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 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: NA
Last verified: October 2013
History: No changes posted
  Purpose

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 obese children is to determine whether eight weeks of daily supplementation with vitamin K2 (menaquinone-7) can improve markers in blood associated with diabetes risk.


Condition Intervention Phase
Obesity
Insulin Resistance
Insulin Sensitivity
Beta-Cell Dysfunction
Prediabetes
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 2
Phase 3

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: Efficacy and Optimal Dose Finding Study of Vitamin K on 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 change in carboxylation of osteocalcin 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 change in carboxylation of osteocalcin 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., activated thrombin and endogenous thrombin potential) will be assessed at baseline and 8 weeks to determine that vitamin K2 has no procoagulant effect.

  • 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.

  • Effects of sex, race, bone age, and pubertal stage on changes in glucose metabolism (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 Primary Completion Date: August 2014 (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 11 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age 8 to 11 years
  • Obese but otherwise healthy (obese is defined as having body mass index greater than or equal to 95th percentile for children of same age and sex)
  • Sedentary (no regular physical activity or sports program greater than one hour per week)
  • 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, Assistant Professor, Department of Pediatrics, Georgia Regents University
ClinicalTrials.gov Identifier: NCT01972113     History of Changes
Other Study ID Numbers: Pro00000912
Study First Received: October 24, 2013
Last Updated: October 24, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Georgia Regents University:
Vitamin K
Vitamin K2
Menaquinone-7
Osteocalcin
Children
Obesity
Insulin resistance
Insulin sensitivity
Beta-cell function
Prediabetes

Additional relevant MeSH terms:
Insulin Resistance
Obesity
Glucose Intolerance
Prediabetic State
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hyperglycemia
Diabetes Mellitus
Endocrine System Diseases
Vitamin K
Vitamins
Vitamin K 2
Vitamin MK 7
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014