OPG and RANKL Plasma Level After Administration of Unfractionated Heparin (UFH) and Low-Molecular-Weight Heparin (LMWH) in Hemodialysis
Recruitment status was Recruiting
Tracking Information | |||||
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First Received Date ICMJE | April 25, 2008 | ||||
Last Updated Date | April 28, 2008 | ||||
Start Date ICMJE | March 2008 | ||||
Estimated Primary Completion Date | June 2008 (final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Levels of osteoprotegerin after administration of UFH or LMWH used as anticoagulant therapy for hemodialysis [ Time Frame: during and after dialysis sessions ] [ Designated as safety issue: No ] | ||||
Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | Complete list of historical versions of study NCT00669721 on ClinicalTrials.gov Archive Site | ||||
Current Secondary Outcome Measures ICMJE |
Secondary aim of the study is to verify the safety of anticoagulation therapy with UFH and LMWH. [ Time Frame: during and after dialysis sessions ] [ Designated as safety issue: Yes ] | ||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Outcome Measures ICMJE | |||||
Original Other Outcome Measures ICMJE | |||||
Descriptive Information | |||||
Brief Title ICMJE | OPG and RANKL Plasma Level After Administration of Unfractionated Heparin (UFH) and Low-Molecular-Weight Heparin (LMWH) in Hemodialysis | ||||
Official Title ICMJE | Effects of UFH and LMWH on Osteoprotegerin and RANKL Plasma Levels in Hemodialysis Patients | ||||
Brief Summary | A randomised, prospective, cross over study will be done to determine whether the anticoagulation therapy with UFH or LMWH used for hemodialysis sessions modifies osteoprotegerin and RANKL plasma levels. |
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Detailed Description | It's well known that treatment with heparin can lead to a reduction in bone density and the development of osteoporosis [ 1 ]. Until now, it's not clear the mechanism by which heparin produces this side effect, but several studies in animals [ 2,3] and in humans [ 4 ] have shown that LMWH may induce less osteoporosis than UFH. 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]. |
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Study Type ICMJE | Interventional | ||||
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Study Design ICMJE | Allocation: Randomized Endpoint Classification: Bio-equivalence Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Basic Science |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE | 40 | ||||
Estimated Completion Date | June 2008 | ||||
Estimated Primary Completion Date | June 2008 (final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Gender | Both | ||||
Ages | 18 Years and older | ||||
Accepts Healthy Volunteers | No | ||||
Contacts ICMJE | |||||
Location Countries ICMJE | Italy | ||||
Administrative Information | |||||
NCT Number ICMJE | NCT00669721 | ||||
Other Study ID Numbers ICMJE | LWH-INT-79 | ||||
Has Data Monitoring Committee | Yes | ||||
Responsible Party | Prof. Sergio Stefoni, St. Orsola University Hospital | ||||
Study Sponsor ICMJE | St. Orsola Hospital | ||||
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Information Provided By | St. Orsola Hospital | ||||
Verification Date | April 2008 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |