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Purpose

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

Eligibility

Eligible Ages
Over 21 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Aged 21 years or older;
  • Chronic maintenance dialysis of at least 3 months' duration;
  • Osteoporotic by DXA of either spine or total hip (Women: post-menopausal or age ≥ 50 with T-score ≤ -2.5; Men: age ≥ 50 with T-score ≤ -2.5; All others, Z-score ≤ -2.5);
  • Mental competence;
  • Willingness to participate in the study;
  • Normal serum calcium.

Exclusion Criteria

  • Pregnancy or breast feeding;
  • Incarceration;
  • Systemic illnesses or organ diseases that may affect bone (except type 1 or type 2 diabetes mellitus);
  • Clinical condition that may limit study participation (e.g., unstable angina, respiratory distress, infections).
  • Chronic alcoholism and/or drug addiction;
  • Known Paget 's disease of bone;
  • Prior external beam or implant radiation therapy involving the skeleton;
  • More than 3 computed tomography (CT) scans in the prior 12 months (to avoid excessive radiation exposure);
  • Participation in a study of an investigational drug during the past 90 days;
  • Planning to move out of the area within 1 year of the study;
  • On active transplant list;
  • BMD t-score of the radius less than -3.5 by DXA (to avoid the known potential negative effects of teriparatide treatment on BMD of the radius);
  • Planned or anticipated oral surgery within the next 12 months;
  • Inability to stand or sit upright for at least 30 minutes;
  • Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia;
  • Treatment within last 6 months with drugs that may affect bone metabolism including bisphosphonates and teriparatide (except for treatment with calcitriol, vitamin D analogs and/or calcimimetics);
  • Current treatment with medicines containing digoxin or warfarin;
  • Calcidiol level below the normal range. (The current routine clinical practice in our dialysis clinics is to check calcidiol status twice yearly and supplement with vitamin D according to serum calcidiol levels. It is therefore unlikely that a substantial number of patients will be excluded due to this exclusion criterion.)

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • Drug: Alendronate

Recruiting Locations

UK Center for Clinical and Translational Science and nearby locations

University of Kentucky
Lexington, Kentucky 40536
Contact:
Nedda Hughes, PA
859-218-1509
nkhugh1@uky.edu

More Details

NCT ID
NCT02440581
Status
Recruiting
Sponsor
Hartmut Malluche, MD

Study Contact

Hartmut Malluche, MD
859-323-5049
hhmall@uky.edu

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.