To determine if Simvastatin can stimulate bone metabolism while simultaneously attenuate vascular calcification metabolism as quantified by Na18F PET CT imaging.
ID
Source
Brief title
Condition
- Other condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Health condition
Botontkalking (osteoporose)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the absolute change in fluorine-18 metabolism in the
2nd, 3rd, and 4th lumbar vertebral body (quantified by the volumetric bone
metabolic rate; bodyweight corrected standardized uptake value [g/mL]
multiplied by the volume of the vertebral body) between baseline and 3 months
after baseline.
Secondary outcome
Maximum standardized uptake value in the major arteries (aorta, carotid
arteries, coronary arteries) between baseline and three months after baseline.
Background summary
Remarkably, osteopenia and osteoporosis are often accompanied by ectopic artery
calcification, a strong independent risk factor of cardiovascular disease
(CVD). This association is known as the calcification paradox. Simvastatin, an
HMG-CoA reductase inhibitor, is the first-line drug for the primary prevention
of CVD. Recent evidence suggests Simvastatin can also reduce fracture risk in
patients with osteopenia / osteoporosis. We hypothesize that Simvastatin
achieves the reduction of CVD risk and fracture risk by attenuating vascular
calcification metabolism and stimulating bone metabolism, respectively.
Study objective
To determine if Simvastatin can stimulate bone metabolism while simultaneously
attenuate vascular calcification metabolism as quantified by Na18F PET CT
imaging.
Study design
Case-crossover study
Study burden and risks
Each patient will visit the University Medical Center Utrecht thrice: two weeks
before baseline, at baseline, and three months after baseline. At each visit,
questionnaires, blood samples, dual-energy X-ray absorptiometry (DXA) of the
vertebral bodies, femoral necks, and total hips, and a *whole-body* hybrid
sodium fluoride-18 positron emission tomography computed tomography (Na18F PET
CT) scan will be acquired. DXA and Na18F PET CT are associated with exposure to
ionizing radiation. The effective dosage per DXA and per Na18F PET CT is 0.03
mSv and 5.80 mSv, respectively. For the entire study protocol, the effective
dosage is approximately 17.5 mSv. This might marginally increase the lifetime
risk of developing cancer. Research participants gain no individual benefit
from participating in the study. However the study is expected to open up a
promising avenue for the treatment of atherosclerosis, osteopenia, and
osteoporosis. Statins do not only attenuate cardiovascular risk, but might
possibly reduce fracture risk by increasing bone mineral density. Therefore,
evaluating the effect of statins on bone metabolism and vascular calcification
metabolism is especially apposite in patients with decreased bone turnover as
well as an increased cardiovascular risk profile, as are the patients included
in our study.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
1. Statin naivety;
2. Age equal to or above 50 years;
3. T-score at inclusion between -1.0 and -2.5;
4. HeartSCORE equal to or above 5% (i.e. clinical indication for Simvastatine 40 mg determined at the discretion of the treating physician).
5. Karnofsky score at inclusion equal to or higher then 90%.
Exclusion criteria
Reduced bone mass due to drugs (i.e., steroids) or a medical condition, such as
hyperthyroidism, hyperparathyroidism, renal or liver failure, multiple myeloma, etc.;Current or prior treatment with bisphosphonates, calcium-antagonists, calcium supplements with or without vitamin D, PTH-agonists, and Denosumab.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-003360-32-NL |
| CCMO | NL45890.041.13 |