A Randomized, Placebo-controlled, Double Blind Trial to Investigate Whether Vitamin K2 Can Influence Arterial Calcification in Patients With Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
Arterial calcification is an independent predictor of coronary events associated with a 3-4 fold increased risk of cardiovascular events. Currently, no effective intervention exists to reduce arterial calcification. However, recent studies showed that vitamin K may reduce ongoing calcium deposition in the arteries, and thereby inhibit arterial calcification. The primary objective is to determine if MK-7 supplementation leads to stabilization or attenuation of ongoing calcium deposition in the femoral artery as quantified by 18F-NaF PET/CT imaging in patients with type 2 diabetes and arterial disease.

Official Title
-----------------
A Randomized, Placebo-controlled, Double Blind Trial to Investigate Whether Vitamin K2 Can Influence Arterial Calcification in Patients With Type 2 Diabetes

Conditions
-----------------
Arterial Calcification, Diabetes Mellitus Type 2

Intervention / Treatment
-----------------
* Dietary Supplement: Menaquinone-7
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Middle aged men and women, ≥ 40 years. Diagnosed with type 2 diabetes. Presence of arterial diseases, based on an Ankle Brachial Index (ABI) <0.9 and/or diagnosed with arterial diseases by physician. ABI<0.9 Written informed consent. Exclusion Criteria: Subjects participate in another intervention research or study using imaging. Contra-indication for undergoing18F-NaF PET/CT scan (claustrophobia, pregnancy, breastfeeding). Subject underwent amputation of the lower extremities (above the knee). Using vitamin K antagonists. Known coagulation problems (history of Venous Thrombo Embolism). Using vitamin supplements that contain vitamin K, or unwilling to stop two weeks before randomisation. A mean vitamin K2 intake ≥120 microgram/day measured with a questionnaire. Natto or goose liver consumers. Low kidney function (eGFR<30).

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin K<br>One group receives tablets of 360 microgram menaquinone-7 daily | Dietary Supplement: Menaquinone-7<br> <br> |
| Placebo Comparator: Placebo<br>One group receives placebo tablets daily | Dietary Supplement: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in ongoing calcium deposition quantified as volumetric bone metabolic rate (CSUVMEAN x cm3) in the femoral artery between baseline and 6 months after baseline, as determined by 18F-NaF PET/CT imaging. |  | 6 months |