Clinical trial NCT01574963: Graz Osteoprotegerin as a Risk Factor (GORF) Study
Official title: Graz Osteoprotegerin as a Risk Factor (GORF) Study: THE ROLE of OSTEOPROTEGERIN (OPG) and the RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-Kb LIGAND (RANKL) IN PATIENTS REQUIRING SURGERY FOR CORONARY HEART DISEASE
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Prevalent OPG and RANKL Excession in Patients With CAD
Keywords: Coronary artery disease
OPG
RANKL
bone disease
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
Collaborators: name: Medical University of Vienna
First posted: 2012-04-10
Enrollment: 150
Sex: MALE
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male patients above 40 years of age presenting with symptomatic CAD and scheduled for a coronary artery bypass graft (CABG) are eligible for the study. The control group includes male patients scheduled for elective surgery other than cardiac procedures.

Brief summary: Osteoprotegerin (OPG) is membrane bound in the immune system but can also be produced and secreted almost everywhere in the organism, so that it is mainly available in soluble form. So far, the OPG/RANKL/RANK system has been most intensively studied in bone. The binding of RANKL on its receptor RANK, which is expressed by osteoclasts, activates a number of osteoclastic cell functions. OPG also has a key function in the vascular system. Patients with coronary heart disease (CAD) have elevated OPG serum levels, probably as a sign of ischemic or inflammatory endothelial damage. Elevated OPG levels were also found in patients with advanced heart failure, whereby OPG correlated with pro BNP (brain natriuretic peptide) and was a predictor for cardiovascular morbidity and mortality.

Our prospective cohort study will include 150 men (75 patients requiring surgery for CAD and a control group without coronary heart disease). The primary endpoints are the differences between the two groups in serum levels of OPG and RANKL, markers of bone metabolism (osteocalcin \[OC\], crosslaps \[CTX\], tartrate resistant acid phosphatase (TRAP5b), 25(OH) vitamin D \[Vit D\], 1.25(OH) vitamin D, parathormone \[iPTH\], endocrine parameters related to vascular damage (e.g. aldosterone, renin and cortisol) and bone mineral density. Metabolomic based biomarkers will be evaluated to explore the mechanisms behind OPG-RANKL linked CVD damage. In the patients further studies of the mRNA expression of OPG, RANKL, TRAP5b, arginine:glycine amidinotransferase (AGAT) and osteocalcin in bone (sternum sliver) and vascular wall (aorta, internal thoracic artery and the great saphenous vein) will be performed.

A further study endpoint is the analysis of a causal coincidence between osteoporosis and CAD and the discrimination of possible key factors in the two entities. These will be determined by the correlation between the above-mentioned markers in serum and the expression in different vessels and in bone tissue.

In addition to analysis of the degree of vascular sclerosis, the mineral content of the bone will also be analyzed in a subpopulation with quantitative backscattered electron imaging (qBEI) related to the degree of vascular sclerosis and bone mineral density. The ultimate goal of the analysis is the discrimination of the most sensitive predictive marker(s) for diagnosis and outcome of patients with CAD for the purpose of early diagnosis and primary prevention of the disease.

CAD and osteoporosis are increasingly prevalent diseases that overlap. In both entities, OPG plays a role not only in pathogenesis but also as an outcome predictor. We aim to study the relevance of OPG concentration in serum but also in the vessel wall and the bone.


Eligibility criteria: Inclusion Criteria:

* Male patients above 40 years of age presenting with symptomatic CAD and scheduled for a coronary artery bypass graft (CABG) are eligible for the study. The control group includes male patients scheduled for elective surgery other than cardiac procedures.

Exclusion Criteria:

* Exclusion criteria are a second indication for heart surgery, chronic renal disease with a glomerular filtration rate \< 30ml/min, advanced liver disease (AST, ALT, GGT \> 3fold upper limit of normal), history of malignancy within the last 5 years and ongoing osteoprotective treatment.

Primary outcomes:
measure: OSTEOPROTEGERIN (OPG)
timeFrame: Baseline at time 0 (at the beginning of the study). The participants will be followed for the duration of hospital stay, an expected average of 10 days.
Secondary outcomes:
measure: RANKL
timeFrame: At baseline. The participants will be followed for the duration of hospital stay, an expected average of 10 days.
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
Study officials:
affiliation: Medical University of Graz, Department of Surgery, Division for Cardiac Surgery
name: Daniela Malliga, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of Graz, Department of Internal Medicine, Division for Endocrinology and Metabolism
name: Astrid Fahrleitner-Pammer, Prof.
role: STUDY_DIRECTOR
affiliation: Medical University of Graz, Department of Surgery, Division for Transplantation
name: Doris Wagner, MD
role: STUDY_CHAIR
References: