Vitamin D and Carboxy PTH Fragments in Coronary Calcification

This study has been withdrawn prior to enrollment.
(study never initiated)
Sponsor:
Information provided by:
Southeast Renal Research Institute
ClinicalTrials.gov Identifier:
NCT00502268
First received: July 16, 2007
Last updated: July 20, 2011
Last verified: July 2011
  Purpose

Arterial calcification within the coronaries and other vessels is greatly accelerated among patients with chronic or end-stage kidney disease. The mechanisms leading to increased calcification are unknown, but include hyperphosphatemia, hyperparathyroidism and altered vitamin D metabolism. Moreover, recent data demonstrates that circulating carboxy fragments of PTH (7-84) are physiologic antagonists of intact PTH (1-84) and may directly contribute to vascular calcification. Current PTH assays no not distinguish between intact and carboxy PTH fragments leading to an overestimation of intact PTH levels. Because second generation PTH assays detect both 1-84 and 7-84 PTH fragments, the use of vitamin D analogues to treat secondary hyperparathyroidism could lead to excessive suppression of 1-84 and a preponderance of carboxy PTH fragments. Moreover, increased administration of vitamin D analogues amy contribute to vascular calcifications. To investigate these questions, we plan to investigate the effect of managing new ESRD patients using conventional and third generation PTH assays on vitamin D administration and the development of coronary calcification. Hypothesis #1: Clinical management of secondary hyperparathyroidism in new hemodialysis patients using the Scantibodies 1-84/7-84 PTH ratio for one year will reduce the amount of Vitamin D administration resulting in reduced coronary calcification compared to patients in which PTH management is accomplished by conventional, second generation PTH assay.


Condition Intervention Phase
Coronary Calcification
Endstage Renal Disease
Parathyroid Hormone
Drug: Doxercalciferol administration
Drug: Doxercalciferol administered by 1-84-7-84
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: A Prospective, Randomized, Open-Label Trial Investigating the Effect of 1 Alpha Hydroxy Vitamin D2 on the Development of Coronary Calcification in New ESRD Patients Using the 1-84/7-84 PTH Ratio to Determine Dosing

Resource links provided by NLM:


Further study details as provided by Southeast Renal Research Institute:

Primary Outcome Measures:
  • Percent Change in Hounsfield units of coronary calcification between baseline and after one year of therapy [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mean dose of Vitamin D2 administered over 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: February 2008
Study Completion Date: July 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Group 1
Doxercalciferol administration by DOQI and 2nd Gen PTH assay
Drug: Doxercalciferol administration
Doxercalciferol administration
Active Comparator: Group 2
Doxercalciferol administered by 1-84-7-84 ratio between 1.4-1.6
Drug: Doxercalciferol administered by 1-84-7-84
Doxercalciferol administered by 1-84-7-84

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient age > 18 and < 80 years of age
  2. Patients receiving outpatient hemodialysis for > 3 or <24 months duration
  3. Patients must have baseline coronary calcification defined as at one ROI (regions of interest with >130 Hounsfield units) in 1 or more coronary vessels
  4. Patients must have a stable dose of phosphate binder for 30 days prior to study enrollment

Exclusion Criteria:

  1. Patients intact PTH < 100 or > 1000 pg/ml
  2. Patients on peritoneal dialysis
  3. Patients with a previous parathyroidectomy
  4. Patients with dry weight > 300 lbs
  5. Patients with chronic atrial flutter or fibrillation
  6. Patients receiving chronic coumadin therapy
  7. Patients with known allergies to contrast dyes
  8. Patients receiving current Cinacalcet therapy or during previous 30 days
  9. Patients unable to take Metoprolol therapy
  10. Patients with resting heart rate >100 and unresponsive to beta blockade
  11. Patients with known pregnancy or unwilling to use contraception during the course of the study
  12. Patients unable to tolerate the confines of CT scanner
  13. Patients with a renal transplant within the previous 5 years
  14. Patients with known aluminum toxicity
  15. Patients undergoing recent PTCA or CABG within the previous 12 months
  16. Patients with ESRD secondary to Sarcoidosis
  17. Patients unwilling to use Selevamer as a primary phosphate binder
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00502268

Locations
United States, North Carolina
Davita East Charlotte Dialysis Unit
Charlotte, North Carolina, United States, 28208
Sponsors and Collaborators
Southeast Renal Research Institute
Investigators
Principal Investigator: James A. Tumlin, MD Southeast Renal Research Institute
  More Information

No publications provided

Responsible Party: James A. Tumlin MD, Southeast Renal Research Institute
ClinicalTrials.gov Identifier: NCT00502268     History of Changes
Other Study ID Numbers: SBPTH-CC1
Study First Received: July 16, 2007
Last Updated: July 20, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Southeast Renal Research Institute:
Coronary Calcification
Endstage Renal Disease
Parathyroid hormone

Additional relevant MeSH terms:
Calcinosis
Kidney Diseases
Kidney Failure, Chronic
Calcium Metabolism Disorders
Metabolic Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
1 alpha-hydroxyergocalciferol
Vitamin D
Ergocalciferols
Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on April 15, 2014