Dose-Finding Study for Vitamin K2 in Human Volunteers - Full Text View

Purpose

Earlier studies have shown that high vitamin K-intake leads to improved bone and vascular health by increased carboxylation of Gla-proteins in these tissues. From all K-vitamins, menaquinone-7 (MK-7) has been identified as the most effective cofactor for the carboxylation reaction of Gla-proteins such as osteocalcin and matrix-gla protein. The question remains which dosage of MK-7 leads to optimal carboxylation levels of these proteins.

The primary objective of this double-blind randomized intervention study is to establish the optimal dose of MK-7 for carboxylation of the vitamin K-dependent proteins osteocalcin in bone and matrix-gla protein in the vessel wall. The optimal dose will be the concentration at which osteocalcin and matrix-gla protein are > 90% in the active (=carboxylated) form.

Condition	Intervention
Vitamin K-Status	Dietary Supplement: no vitamin K Dietary Supplement: 10 mcg Vitamin K for 3 months daily Dietary Supplement: 20 mcg Vitamin K for 3 months daily Dietary Supplement: 45 mcg Vitamin K for 3 months daily Dietary Supplement: 90 mcg Vitamin K for 3 months daily Dietary Supplement: 180 mcg Vitamin K for 3 months daily Genetic: 360 mcg Vitamin K for 3 months daily

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Dose-Finding Study for Vitamin K2 in Human Volunteers

Resource links provided by NLM:

MedlinePlus related topics: Vitamin K

Drug Information available for: Menadione

U.S. FDA Resources

Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:

undercarboxylated osteocalcin [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
carboxylated osteocalcin [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

undercarboxylated matrix-gla protein [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
carboxylated matrix-gla protein [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment:	42
Study Start Date:	May 2007
Study Completion Date:	October 2007
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
No Intervention: 1	Dietary Supplement: no vitamin K no vitamin K
Active Comparator: 2 10 mcg Vitamin K	Dietary Supplement: 10 mcg Vitamin K for 3 months daily 10 mcg Vitamin K for 3 months daily
Active Comparator: 3 20 mcg Vitamin K	Dietary Supplement: 20 mcg Vitamin K for 3 months daily 20 mcg Vitamin K for 3 months daily
Active Comparator: 4 45 mcg Vitamin K	Dietary Supplement: 45 mcg Vitamin K for 3 months daily 45 mcg Vitamin K for 3 months daily
Active Comparator: 5 90 mcg Vitamin K	Dietary Supplement: 90 mcg Vitamin K for 3 months daily 90 mcg Vitamin K for 3 months daily
Active Comparator: 6 180 mcg Vitamin K	Dietary Supplement: 180 mcg Vitamin K for 3 months daily 180 mcg Vitamin K for 3 months daily
Active Comparator: 7 360 mcg Vitamin K for 3 months daily	Genetic: 360 mcg Vitamin K for 3 months daily 360 mcg Vitamin K for 3 months daily

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy male and female adults between 18 and 45 years of age.
Subjects of normal body weight and height according to BMI < 30
Subject has given written consent to take part in the study

Exclusion Criteria:

Subjects with (a history of) metabolic or gastrointestinal disease
Subject with (a history of) soy allergy
Subjects using vitamin supplements containing vitamin K
Subjects presenting chronic inflammatory diseases
Subjects receiving systemic treatment or topical treatment likely to interfere with evaluation of the study parameters
Subjects receiving corticoϊd treatment
Subjects using oral anticoagulants

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00483431

Locations

Netherlands
VitaK BV / University of Maastricht
Maastricht, PO Box 616, Netherlands, 6200 MD

Sponsors and Collaborators

Maastricht University Medical Center

Investigators

Principal Investigator:

Cees Vermeer, PhD

Maastricht University

More Information

No publications provided by Maastricht University Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Theuwissen E, Cranenburg EC, Knapen MH, Magdeleyns EJ, Teunissen KJ, Schurgers LJ, Smit E, Vermeer C. Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. Br J Nutr. 2012 Nov 14;108(9):1652-7. doi: 10.1017/S0007114511007185. Epub 2012 Jan 31.

Knapen MH, Schurgers LJ, Shearer MJ, Newman P, Theuwissen E, Vermeer C. Association of vitamin K status with adiponectin and body composition in healthy subjects: uncarboxylated osteocalcin is not associated with fat mass and body weight. Br J Nutr. 2012 Sep 28;108(6):1017-24. doi: 10.1017/S000711451100626X. Epub 2011 Dec 5.

Responsible Party:	Dr.C.Vermeer, VitaK BV
ClinicalTrials.gov Identifier:	NCT00483431 History of Changes
Other Study ID Numbers:	MEC 07-3-014
Study First Received:	June 6, 2007
Last Updated:	March 9, 2009
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht University Medical Center:

vitamin K2
dosis-response
osteocalcin
matrix-gla protein

Additional relevant MeSH terms:

Vitamin K
Vitamins
Vitamin K 2
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 May 23, 2013