Vitamin D and Carboxy PTH Fragments in Coronary Calcification

NCT00502268 | Withdrawn Phase 4

• 1 other identifier: SBPTH-CC1
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Coronary Calcification; Endstage Renal Disease; Parathyroid Hormone

Keywords

Coronary Calcification; Endstage Renal Disease; Parathyroid hormone

Outcome Measures

Primary Outcomes (1)

• Percent Change in Hounsfield units of coronary calcification between baseline and after one year of therapy

  12 months

Secondary Outcomes (1)

• Mean dose of Vitamin D2 administered over 12 months

  12 months

Study Arms (2)

Group 1

PLACEBO COMPARATOR

Doxercalciferol administration by DOQI and 2nd Gen PTH assay

Drug: Doxercalciferol administration

Group 2

ACTIVE COMPARATOR

Doxercalciferol administered by 1-84-7-84 ratio between 1.4-1.6

Drug: Doxercalciferol administered by 1-84-7-84

Interventions

Doxercalciferol administration DRUG

Doxercalciferol administration

Group 1

Doxercalciferol administered by 1-84-7-84 DRUG

Doxercalciferol administered by 1-84-7-84

Group 2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients intact PTH \< 100 or \> 1000 pg/ml
• Patients on peritoneal dialysis
• Patients with a previous parathyroidectomy
• Patients with dry weight \> 300 lbs
• Patients with chronic atrial flutter or fibrillation
• Patients receiving chronic coumadin therapy
• Patients with known allergies to contrast dyes
• Patients receiving current Cinacalcet therapy or during previous 30 days
• Patients unable to take Metoprolol therapy
• Patients with resting heart rate \>100 and unresponsive to beta blockade
• Patients with known pregnancy or unwilling to use contraception during the course of the study
• Patients unable to tolerate the confines of CT scanner
• Patients with a renal transplant within the previous 5 years
• Patients with known aluminum toxicity
• Patients undergoing recent PTCA or CABG within the previous 12 months

Sponsors & Collaborators

• Southeast Renal Research Institute: lead

Study Sites (1)

Davita East Charlotte Dialysis Unit

Charlotte, North Carolina, 28208, United States

Location

Study Officials

• James A. Tumlin, MD

  Southeast Renal Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Nurse

Study Record Dates

• First Submitted: July 16, 2007
• First Posted: July 17, 2007
• Study Start: February 1, 2008
• Primary Completion: February 1, 2009
• Study Completion: July 1, 2009
• Last Updated: December 23, 2020

Record last verified: 2020-12

Locations

US (1)