The primary objective is to determine if MK-7 supplementation leads to stabilization or attenuation of ongoing calcium deposition, quantified by 18F- NaF PET/CT imaging in patients with type 2 diabetes.
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Ongoing calicum deposition in the femoral artery, quantified by 18F-NaF PET/CT
imaging.
Secondary outcome
- Ongoing calcium deposition in other arteries than the femoral artery, as
quantified by 18F-NaF PET/CT imaging
- Ongoing calcium deposition in the lumbar spine, as quantified by 18F-NaF
PET/CT imaging
- Arterialstiffness, as quantified by pulsecor.
- Dpuc-MGP, as quantified using a sandwich ELISA.
Background summary
Arterial calcification is an important riskfactor for cardio vascular diseases.
Observational studies has shown that vitamin K may reduce or attenuated the
proces of ongoing calcium deposition. This could be explained by matrix gla
protein (MGP), which is a vitamin K dependent protein. A previous study within
our working group has shown that vitamin K supplementation reduce the inactive
MGP (dpuc-MGP). Other studies showed that a decrease in inactive MGP reduce the
risk of ongoing calcium deposition in the arteries. Therefore this study is
conducted to investigate whether vitamin K supplementation reduces or
attenuated ongoing calcium deposition in the arteries.
Study objective
The primary objective is to determine if MK-7 supplementation leads to
stabilization or attenuation of ongoing calcium deposition, quantified by 18F-
NaF PET/CT imaging in patients with type 2 diabetes.
Study design
Double blind randomized placebo-controlled trial, with a follow up of 6 months.
Intervention
Subjects will be randomized, one group receives daily 360 µg tablets of MK-7
and the other group receives daily placebo tablets during 6 months
Study burden and risks
Each patient will visit the UMC Utrecht 4 times for the 6 months duration of
the study. At screening, baseline, after 3 months and after 6 months. At
baseline and after 6 months a *whole-body* 18F-NaF PET/CT scan will be made as
part of the study, to measure ongoing calcium deposition in the arteries and
lumbar spine. One group of participants will receive vitamin K during 6 months.
The doses of this supplement is within the physiologic borders and therefore
not harmful. Also a 3-day food diary will be acquired at baseline and a weekly
compliance questionnaire. Blood samples will be taken at baseline and after 3
and 6 months of follow-up. The burden is relatively high but the risk is low.
Previous studies showed no harmfull effect of vitamin K, and the dosages of
radioactivity is approximately 11.6 mSv. Due to the radiation of 11.6 mSv from
this study, the cancer risk for a 60 year old male increases with 0.04%, given
a normal life expectancy. Furthermore, our study participants will probably be
older, because the mean age of our study population in the Diabetes Pearl
cohort is 68 years. Atom bomb data suggest a delay of several decades between
exposure and the occurrence of solid tumours. So, theoretically the PET-CT
increases the risk of cancer, but in our cohort with diabetes patients with
arterial disease the risk will be very low.
Universiteitsweg 100
Utrecht 3584 CX
NL
Universiteitsweg 100
Utrecht 3584 CX
NL
Listed location countries
Age
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. Arterial disease is defined as:
* Coronary artery disease: angina pectoris, myocardial infarction, coronary revascularization (bypass surgery or angioplasty), or
* Cerebral vascular disease: transient ischemic attack, cerebral infarction, amaurosis fugax, retinal infarction, history of carotid surgery, or
* Peripheral artery disease: symptomatic and documented obstruction of distal arteries of the leg or surgery of the leg (percutaneous transluminal angioplasty, bypass or amputation), or
* Abdominal aortic aneurysm: supra- / infrarenal aneurysm of the aorta (distal aorta anteroposterior diameter * 3 cm, measured with ultrasonography) or a history of AAA surgery, or,
-Written informed consent.
Exclusion criteria
- Subjects participates in another intervention research or study using imaging.
- Contra-indication for undergoing18F-NaF PET/CT scan (claustrophobic patients, pregnancy, breastfeeding).
- Subject underwent amputation of the lower extremities (above the knee).
- Using vitamin K antagonists.
- Known coagulation problems (e.g. history of Venous Trombo Embolism, or polycythemia vera).
- Plasma or blood donor and unwilling to stop during this intervention research.
- Using vitamin supplements that contain vitamin K, or unwilling to stop two weeks before randomisation. If the participants use vitamin D or calcium supplements, it should be constant during the study.
- A mean vitamin K2 intake *120 *g/day measured with a questionnaire.
- Natto or goose liver consumers.
- Known with low kidney function (eGFR <30)
- Incompressible femoral artery, as diagnosed by a physician.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL53572.041.15 |
| OMON | NL-OMON25255 |