Graz Osteoprotegerin as a Risk Factor (GORF) Study

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2012 by Medical University of Graz.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Medical University of Vienna
Information provided by (Responsible Party):
Daniela Malliga, MD, Medical University of Graz
ClinicalTrials.gov Identifier:
NCT01574963
First received: April 4, 2012
Last updated: April 9, 2012
Last verified: April 2012
  Purpose

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.


Condition
Prevalent OPG and RANKL Excession in Patients With CAD

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
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

Resource links provided by NLM:


Further study details as provided by Medical University of Graz:

Primary Outcome Measures:
  • OSTEOPROTEGERIN (OPG) [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • RANKL [ Time Frame: At baseline. The participants will be followed for the duration of hospital stay, an expected average of 10 days. ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 150
Study Start Date: July 2010
Estimated Study Completion Date: September 2012
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
CAD Patients
Patients suffering from CAD requiring coronary artery bypass grafting
Control Patients
Patients without CAD

  Eligibility

Ages Eligible for Study:   40 Years to 90 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01574963

Contacts
Contact: Daniela Malliga, MD 0043 316 385 ext 80651 daniela-eugenia.martin@medunigraz.at
Contact: Doris Wagner, MD 0043 316 385 ext 80651 doris.wagner@medunigraz.at

Locations
Austria
Medical University of Graz Recruiting
Graz, Austria, 8036
Contact: Daniela Malliga, MD    0043 316 385 ext 80681    daniela-eugenia.martin@medunigraz.at   
Contact: Doris Wagner, MD    0043 316 385 ext 80651    doris.wagner@medunigraz.at   
Sponsors and Collaborators
Medical University of Graz
Medical University of Vienna
Investigators
Principal Investigator: Daniela Malliga, MD Medical University of Graz, Department of Surgery, Division for Cardiac Surgery
Study Director: Astrid Fahrleitner-Pammer, Prof. Medical University of Graz, Department of Internal Medicine, Division for Endocrinology and Metabolism
Study Chair: Doris Wagner, MD Medical University of Graz, Department of Surgery, Division for Transplantation
  More Information

No publications provided

Responsible Party: Daniela Malliga, MD, OA Dr. med. univ., Medical University of Graz
ClinicalTrials.gov Identifier: NCT01574963     History of Changes
Other Study ID Numbers: GORF 2.0
Study First Received: April 4, 2012
Last Updated: April 9, 2012
Health Authority: Austria: Medical University of Graz, Ethics board

Keywords provided by Medical University of Graz:
Coronary artery disease
OPG
RANKL
bone disease

ClinicalTrials.gov processed this record on September 18, 2014