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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 15, 2019
Sponsor:
Collaborators:
Wright State University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Hartmut Malluche, MD, University of Kentucky

Tracking Information
First Submitted Date  ICMJE May 7, 2015
First Posted Date  ICMJE May 12, 2015
Last Update Posted Date May 15, 2019
Study Start Date  ICMJE July 2015
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 12, 2015)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 7, 2015)
QCT BMD of the Hip [ Time Frame: One Year ]
At one year we will asses bone mass using QCT of the total hip and compare one year changes in bone mass between the treatment and control groups.
Change History Complete list of historical versions of study NCT02440581 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2015)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2015)
  • Coronary Artery Calcifications by MDCT [ Time Frame: One year ]
    At one year we 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Renal Osteodystrophy: An Individual Management Approach
Official Title  ICMJE Renal Osteodystrophy: A Fresh Approach
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Kidney Failure, Chronic
Intervention  ICMJE
  • Drug: Alendronate
  • Drug: Teriparatide
  • Drug: Cinacalcet
Study Arms  ICMJE
  • 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.
    Interventions:
    • 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.
    Intervention: Drug: Alendronate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 7, 2015)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Hartmut Malluche, MD 859-323-5049 hhmall@uky.edu
Contact: Nedda Hughes, PA 859-218-1509 nkhugh1@uky.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02440581
Other Study ID Numbers  ICMJE 14-0976-F6A
R01DK080770 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hartmut Malluche, MD, University of Kentucky
Study Sponsor  ICMJE Hartmut Malluche, MD
Collaborators  ICMJE
  • Wright State University
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: Hartmut Malluche, MD University of Kentucky
PRS Account University of Kentucky
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP