OPG and RANKL Plasma Level After Administration of Unfractionated Heparin (UFH) and Low-Molecular-Weight Heparin (LMWH) in Hemodialysis
NCT ID: NCT00669721
Last Updated: 2008-04-30
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
UNKNOWN
NA
40 participants
INTERVENTIONAL
2008-03-31
2008-06-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Recently it was observed that heparin interferes with RANK/RANKL/POG system \[5,6\]. RANK, RANKL and OPG are members of TNF alfa receptor superfamily. The pathways involving them in conjunction with various cytokines and calciotrophic hormones play a pivotal role in bone remodelling. In addiction experimental and clinical studies established a consistent relationship between the RANK/RANKL/OPG pathway and both skeletal lesion related to disorders of mineral metabolism \[7,8,9\] and vascular calcification \[7,10\]. OPG exists either as active soluble form or is expressed by osteoblast, stromal and cardiovascular cells, acting as decoy receptor that competes with RANKL for RANK.
This interaction inhibits osteoclastic proliferation and differentiation and consequently prevents bone resorption . OPG is also produced by both endothelial cells (EC) and Vascular Smooth Muscle Cells (VSMCs ). EC-derived OPG seems to act as an important autocrine / paracrine factor able to protect against arterial calcification blocking the effects of RANKL that promotes monocytes differentiation in osteoclast -like cells and an osteogenic differentiation program in VSMC. This process leads to the synthesis of bone proteins and matrix calcification within the arterial vessel. OPG levels increase with aging and are higher in ESRD patient \[11,12\].
Recently it was demonstrated in cultures of murine bone marrow that the heparin inhibits osteoprotegerin activity binding OPG competitively and in this way inhibiting the interaction between OPG and RANKL \[5\].
On the other side heparin seems cause the mobilization of OPG into the circulation. It was reported that OPG is co-localized with vWF in Weibel Palade bodies in endothelial cells \[13\] and binds to Glucosaminoglycans (GAGs) at cellular membranes through its highly basic heparin binding domain \[14,15\]. Heparin treatment causes an immediate mobilization of these protein in to the circulation by displacement from the endothelial surface since they have higher affinity for heparins than GAGs at the endothelial surface\[16,17\]. UFH cause a more pronounced vascular mobilization of OPG than LMWH, indicating that UFH have an higher affinity for OPG than LMWH \[6\].
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
CROSSOVER
BASIC_SCIENCE
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
A
This patients start a run in period with LMWH schedule as hemodialysis circuit anticoagulation. Then they'll undergo hemodialysis with LMWH for a second period of two weeks: in this checking phase samples will be collected during the midweek hemodialysis sessions. After the checking phase the patients will be crossed to UFH schedule. A wash out period of two weeks with UFH will be done. At the end of this period two weeks of checking phase will starts.
law molecular weigth heparin
administration of LMWH as anticoagulation for hemodialysis circuit;nadroparin is administred ad the dosage of 65 IU/kg on starting dialysis and in the arterial hemodialytic line after a washing phase with 2 litres of a heparin-free saline solution 0.9%.
B
The patients randomized to receive UFH will start a run in period with this heparin schedule. Then they'll undergo hemodialysis with UFH for a second period of two weeks: in this checking phase samples will be collected during the midweek hemodialysis sessions. After the checking phase the patients will be crossed to LMWH. A wash out period of two weeks with UFH will be done. At the end of this period two weeks of checking phase will starts.
unfractioned heparin
administration of UFH as anticoagulation of hemodialysis circuit; standard heparin ( Sodic Heparin, Vister by Parke-Davis) 1500 IU on starting dialysis and 1500 ± 500 IU in continues intradialytic infusion per dialysis session
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
law molecular weigth heparin
administration of LMWH as anticoagulation for hemodialysis circuit;nadroparin is administred ad the dosage of 65 IU/kg on starting dialysis and in the arterial hemodialytic line after a washing phase with 2 litres of a heparin-free saline solution 0.9%.
unfractioned heparin
administration of UFH as anticoagulation of hemodialysis circuit; standard heparin ( Sodic Heparin, Vister by Parke-Davis) 1500 IU on starting dialysis and 1500 ± 500 IU in continues intradialytic infusion per dialysis session
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. clinical stability at least three months before the study started;
Exclusion Criteria
2. hemorrhagic stroke
3. Myeloproliferative disorders
4. Hereditary deficiency of coagulation factors, LAC phenomenon or antiphospholipid syndrome
5. Malignant disease
6. Patient submitted to antithrombotic prophylaxis with LMWH
7. Immunosuppressive therapy
8. Participation in other clinical trials
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
IRCCS Azienda Ospedaliero-Universitaria di Bologna
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
St. Orsola University Hospital
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Sergio Stefoni, Prof
Role: PRINCIPAL_INVESTIGATOR
St.orsola University Hospital
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
St.Orsola University Hospital
Bologna, , Italy
Countries
Review the countries where the study has at least one active or historical site.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Sergio Stefoni, Prof.
Role: primary
References
Explore related publications, articles, or registry entries linked to this study.
Muir JM, Hirsh J, Weitz JI, Andrew M, Young E, Shaughnessy SG. A histomorphometric comparison of the effects of heparin and low-molecular-weight heparin on cancellous bone in rats. Blood. 1997 May 1;89(9):3236-42.
Pettila V, Leinonen P, Markkola A, Hiilesmaa V, Kaaja R. Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin. Thromb Haemost. 2002 Feb;87(2):182-6.
Irie A, Takami M, Kubo H, Sekino-Suzuki N, Kasahara K, Sanai Y. Heparin enhances osteoclastic bone resorption by inhibiting osteoprotegerin activity. Bone. 2007 Aug;41(2):165-74. doi: 10.1016/j.bone.2007.04.190. Epub 2007 May 5.
Vik A, Brodin E, Sveinbjornsson B, Hansen JB. Heparin induces mobilization of osteoprotegerin into the circulation. Thromb Haemost. 2007 Jul;98(1):148-54.
Collin-Osdoby P. Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin. Circ Res. 2004 Nov 26;95(11):1046-57. doi: 10.1161/01.RES.0000149165.99974.12.
Vega D, Maalouf NM, Sakhaee K. CLINICAL Review #: the role of receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/osteoprotegerin: clinical implications. J Clin Endocrinol Metab. 2007 Dec;92(12):4514-21. doi: 10.1210/jc.2007-0646. Epub 2007 Sep 25.
Orita Y, Yamamoto H, Kohno N, Sugihara M, Honda H, Kawamata S, Mito S, Soe NN, Yoshizumi M. Role of osteoprotegerin in arterial calcification: development of new animal model. Arterioscler Thromb Vasc Biol. 2007 Sep;27(9):2058-64. doi: 10.1161/ATVBAHA.107.147868. Epub 2007 Jul 5.
Nitta K, Akiba T, Uchida K, Otsubo S, Takei T, Yumura W, Kabaya T, Nihei H. Serum osteoprotegerin levels and the extent of vascular calcification in haemodialysis patients. Nephrol Dial Transplant. 2004 Jul;19(7):1886-9. doi: 10.1093/ndt/gfh263. Epub 2004 May 5.
Schoppet M, Shroff RC, Hofbauer LC, Shanahan CM. Exploring the biology of vascular calcification in chronic kidney disease: what's circulating? Kidney Int. 2008 Feb;73(4):384-90. doi: 10.1038/sj.ki.5002696. Epub 2007 Nov 28.
Zannettino AC, Holding CA, Diamond P, Atkins GJ, Kostakis P, Farrugia A, Gamble J, To LB, Findlay DM, Haynes DR. Osteoprotegerin (OPG) is localized to the Weibel-Palade bodies of human vascular endothelial cells and is physically associated with von Willebrand factor. J Cell Physiol. 2005 Aug;204(2):714-23. doi: 10.1002/jcp.20354.
Standal T, Seidel C, Hjertner O, Plesner T, Sanderson RD, Waage A, Borset M, Sundan A. Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells. Blood. 2002 Oct 15;100(8):3002-7. doi: 10.1182/blood-2002-04-1190.
Theoleyre S, Kwan Tat S, Vusio P, Blanchard F, Gallagher J, Ricard-Blum S, Fortun Y, Padrines M, Redini F, Heymann D. Characterization of osteoprotegerin binding to glycosaminoglycans by surface plasmon resonance: role in the interactions with receptor activator of nuclear factor kappaB ligand (RANKL) and RANK. Biochem Biophys Res Commun. 2006 Aug 25;347(2):460-7. doi: 10.1016/j.bbrc.2006.06.120. Epub 2006 Jun 30.
Valentin S, Larnkjer A, Ostergaard P, Nielsen JI, Nordfang O. Characterization of the binding between tissue factor pathway inhibitor and glycosaminoglycans. Thromb Res. 1994 Jul 15;75(2):173-83. doi: 10.1016/0049-3848(94)90066-3.
Hansen JB, Sandset PM, Huseby KR, Huseby NE, Nordoy A. Depletion of intravascular pools of tissue factor pathway inhibitor (TFPI) during repeated or continuous intravenous infusion of heparin in man. Thromb Haemost. 1996 Nov;76(5):703-9.
Deruelle P, Coulon C. The use of low-molecular-weight heparins in pregnancy--how safe are they? Curr Opin Obstet Gynecol. 2007 Dec;19(6):573-7. doi: 10.1097/GCO.0b013e3282f10e33.
Folwarczna J, Sliwinski L, Janiec W, Pikul M. Effects of standard heparin and low-molecular-weight heparins on the formation of murine osteoclasts in vitro. Pharmacol Rep. 2005 Sep-Oct;57(5):635-45.
Vescini F, Buffa A, Sinicropi G. Osteoprotegerina RANKL e RANK nella regolazione dell'ostoclastogenesi. Riv It Biol Med 22: 64-67, 2002.
Natale P, Palmer SC, Ruospo M, Longmuir H, Dodds B, Prasad R, Batt TJ, Jose MD, Strippoli GF. Anticoagulation for people receiving long-term haemodialysis. Cochrane Database Syst Rev. 2024 Jan 8;1(1):CD011858. doi: 10.1002/14651858.CD011858.pub2.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
LWH-INT-79
Identifier Type: -
Identifier Source: org_study_id