Pilot Study Evaluating Doxercalciferol Replacement Therapy in Kidney Transplant Recipients

Pilot Study: Effects of Hectorol (Doxercalciferol) Vitamin D Replacement on Proteinuria, PTH Level and Bone Turnover in Stable Kidney Transplant Recipients: a Single-Blind, Placebo-Controlled Study in Patients Receiving 25-OH Vitamin D3

People with kidney transplants often develop bone disease. One reason for bone disease may be overactivity of a gland in the neck called the parathyroid gland. Overactivity of the parathyroid gland may be caused by lack of Vitamin D in the body. It has recently been discovered that many patients with kidney transplants have low Vitamin D levels. The investigators are examining the effects of doxercalciferol on parathyroid hormone levels, proteinuria and bone turnover markers in people who have had a kidney transplant.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Kidney Transplantation
• Intervention / Treatment: Drug: Doxercalciferol; Drug: 25-OH Vitamin D3; Drug: placebo

Detailed Description

People with kidney transplants often develop bone disease. One reason for bone disease may be overactivity of a gland in the neck called the parathyroid gland. Overactivity of the parathyroid gland may be caused by lack of Vitamin D in the body. It has recently been discovered that many patients with kidney transplants have low Vitamin D levels.

25-OH Vitamin D3 is now recommended to treat kidney transplant patients with low vitamin D levels but it may not be enough to treat the parathyroid problems and bone disease. Doxercalciferol is a form of Vitamin D that has been used to treat bone disease and parathyroid problems in dialysis patients but has not yet been studied in patients with kidney transplants. We are interested in seeing whether doxercalciferol given together with 25-OH Vitamin D3 will be a better treatment for the overactive parathyroid gland and bone disease than 25-OH Vitamin D3 alone in patients with kidney transplants.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Brooklyn, New York, United States, 11234
      • SUNY Downstate Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults of both genders between the ages of 18 and 65.
• Kidney transplant at least 1 year prior to enrollment
• Creatinine value of <2.5 mg/dl with no excursion >0.5 within the past 3 months
• Proteinuria of 500 mg/24 hours or a protein/creatinine ratio of 0.5 or greater
• Hypovitaminosis D, as defined by a 25-OH Vitamin D value of <25 ng/ml
• Intact PTH value between 150 and 600 pg/ml

Exclusion Criteria:

• History of parathyroidectomy
• History of prior intolerance to vitamin D therapy (not including hypercalcemia)
• History of biopsy proven acute rejection over the 3 months preceding enrollment
• Recent (over the past month) addition of an ACE inhibitor or Angiotensin -
• Receptor Blocking agent - patients who have been on a stable dose are acceptable
• Current use of active Vitamin D supplement (patients in whom therapy has been discontinued more than 1 month prior to enrollment are acceptable)
• Postmenopausal woman or women receiving hormone replacement therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doxercalciferol; Patients are randomized using an A B C D randomization scheme in which the patient and the primary investigator are blinded but the study staff is not. Active group receives doxercalciferol (Hectorol) 1mcgwith active titration based on intact PTH plus 25-OH Vitamin D3 (cholecalciferol) 400 IU. Safety labs and end point labs are monitored as per protocol, with the opportunity to increase the dose of doxercalciferol if target PTH value is not achieved by the predetermined midpoint.	Drug: Doxercalciferol; Active group receives doxercalciferol (Hectorol) 1mcg; Other Names: Hectorol (the other name for Doxercalciferol); Drug: 25-OH Vitamin D3; All groups received cholecalciferol; Other Names: (cholecalciferol)
Placebo Comparator: Cholecalciferol; Patients are randomized using an A B C D randomization scheme in which the patient and the primary investigator are blinded but the study staff is not. Group 2 receives placebo (dummy bottle with pills resembling doxercalciferol) plus 25-OH Vitamin D3 (cholecalciferol) 400IU. Safety labs and end point labs are monitored as per protocol, with the opportunity to increase the dose of doxercalciferol placebo if target PTH value is not achieved by the predetermined midpoint.	Drug: 25-OH Vitamin D3; All groups received cholecalciferol; Other Names: (cholecalciferol); Drug: placebo; Group 2 receives placebo (dummy bottle with pills resembling doxercalciferol); Other Names: Placebo for doxercalciferol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
- iPTH value of 100 pg/ml or lower	The number of patients achieving the target iPTH value of 100 pg/ml or lower measured. Change in the level of iPTH (baseline as compared with 3 and 6 months) using both absolute value and percent change from baseline.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 1,25 D2 and D3, 25-OH Vitamin D3 levels	The Change in the levels of 1,25 D2 and D3, 25-OH Vitamin D3 levels (baseline as compared with 3 month and end of study)	6 months
Change in FGF-23 levels	The Change in FGF-23 levels (baseline as compared with 3 and 6 months) were measured.	6 months
Change in serum bone turnover markers	The Change in the levels of serum osteocalcin, bone alkaline phosphatase and n-telopeptide of Type I collagen levels (baseline versus 3 and 6 months	6 months
Change in Protein/creatinine ratio	Change in the level of Protein/creatinine ratio and or 24 hour urine for protein (baseline as compared with 3 and 6 months) 6. Change in the level of Protein/creatinine ratio (baseline as compared with 3 and 6 months) The Change in the level of Protein/creatinine ratio (baseline as compared with 3 and 6 months)	6 months

Collaborators and Investigators

• Sponsor: Mariana Markell
• Collaborators: Genzyme, a Sanofi Company
• Investigators: Principal Investigator: Mariana Markell, MD, State University of New York - Downstate Medical Center

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: April 23, 2009
• First Submitted That Met QC Criteria: April 28, 2009
• First Posted (Estimate): April 29, 2009

Study Record Updates

• Last Update Posted (Actual): February 22, 2019
• Last Update Submitted That Met QC Criteria: February 19, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: kidney transplantation; kidney transplant recipients
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Ergocalciferols; 1 alpha-hydroxyergocalciferol
• Other Study ID Numbers: 08-080

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO