Renal Osteodystrophy: An Individual Management Approach
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|ClinicalTrials.gov Identifier: NCT02440581|
Recruitment Status : Recruiting
First Posted : May 12, 2015
Last Update Posted : May 3, 2017
Renal osteodystrophy (ROD) represents the bone histologic abnormalities resulting from loss of renal function. It starts early during the loss of kidney function and is seen in virtually all chronic end stage kidney disease patients on dialysis (CKD-5D). A major component of ROD is bone loss leading to chronic kidney disease (CKD) associated osteoporosis. Debilitating hip fractures occur in patients with CKD at a rate 4.4 times higher than in the general population, with associated high costs, morbidity and an annual mortality of 64%. CKD osteoporosis is distinctly different from post-menopausal osteoporosis. Presently, no uniformly accepted CKD osteoporosis treatment protocol exists because of challenges related to racially specific bone turnover states. Therefore, most physicians are reluctant to treat this disorder despite the profound impact on health and quality of life, and its association with vascular calcifications. These vascular calcifications confer an increased risk for cardiovascular events which are the major cause of the over 20% annual mortality rate in CKD-5D patients.
The goal of the proposed controlled randomized study is to test the concept that CKD osteoporosis can be successfully treated when treatment is individualized by patients' turnover status. The study will demonstrate that reversal of bone loss can be achieved by increasing bone formation in low turnover patients, and by reducing bone resorption in normal or high turnover patients. A second aim of this study is to provide new information whether these treatments will also retard progression of vascular calcifications. Blood tests measuring FGF23, indicators of Wnt pathway activity, bone resorption and formation will be followed to understand potential mechanisms and to evaluate their usefulness for prediction of changes in bone mass and vascular calcifications.
CKD-5D patients with established osteoporosis will be enrolled into one of two treatment arms based on bone turnover status. Each arm will be adaptively randomized by race, age and gender into treatment or control groups. In the low turnover arm, teriparatide combined with cinacalcet will be given, and in the normal or high turnover arm, alendronate will be administered. Bone mineral density will be measured at baseline and after one year of treatment by quantitative computed tomography. Calcifications of the coronaries, aorta and heart valves will also be measured at the same times by multi-detector computed tomography.
If this proof-of-concept study is successful, it will offer a heretofore unavailable treatment for osteoporosis in CKD-5D patients thus changing the prevailing clinical practice paradigm. This will provide immediate benefit to CKD patients by reducing fracture risk, bone pain, and cardiovascular risk, while greatly improving their quality of life. These improvements will also convey major socioeconomic benefits by decreasing the high associated treatment costs. The proposed study is highly relevant to the National Institute of Diabetes and Digestive and Kidney Diseases' mission of disseminating science-based information to improve the health and quality of life for patients with endocrine, metabolic and kidney diseases.
|Condition or disease||Intervention/treatment||Phase|
|Kidney Failure, Chronic||Drug: Alendronate Drug: Teriparatide Drug: Cinacalcet||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Renal Osteodystrophy: A Fresh Approach|
|Study Start Date :||July 2015|
|Estimated Primary Completion Date :||June 2020|
|Estimated Study Completion Date :||June 2020|
No Intervention: Control, low turnover
No intervention in low turnover osteoporosis control group.
Experimental: Treatment, low turnover
Low turnover osteoporosis group treated with teriparatide and cinacalcet.
|Drug: Teriparatide Drug: Cinacalcet|
No Intervention: Control, high turnover
No intervention in high turnover osteoporosis control group.
Experimental: Treatment, high turnover
High turnover osteoporosis group treated with alendronate.
- Quantitative Computed Tomography (QCT) Bone Mineral Density of the Hip [ Time Frame: One Year ]At one year the investigators will asses bone mass using QCT of the total hip and compare one year changes in bone mass between the treatment and control groups.
- Coronary Artery Calcifications by Multiple Detector Computed Tomography (MDCT) [ Time Frame: One year ]At one year the investigators will asses differences between the treatment and control groups in changes in Coronary Artery Calcifications by MDCT.
- Serum biochemical bone markers of bone activity [ Time Frame: Six months and One year ]Bone markers of bone activity tracked over time for changes.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02440581
|Contact: Hartmut Malluche, MDemail@example.com|
|Contact: Nedda Hughes, PAfirstname.lastname@example.org|
|United States, Kentucky|
|University of Kentucky||Recruiting|
|Lexington, Kentucky, United States, 40536|
|Contact: Nedda Hughes, PA 859-218-1509 email@example.com|
|Contact: Kim McLaughlin, PA 859-323-2672 firstname.lastname@example.org|
|Principal Investigator:||Hartmut Malluche, MD||University of Kentucky|