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Vitamin D and Coronary Calcification Study (VCOR)

Primary Purpose

Chronic Kidney Disease, Vitamin D Deficiency, Coronary Calcification

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Calcitriol (Rocaltrol®)
Paricalcitol
Sponsored by
Joslin Diabetes Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Chronic Kidney Disease focused on measuring Secondary Hyperparathryoidism, Chronic Kidney Disease, Vitamin D, Coronary Calcification, Bone metabolism

Eligibility Criteria

25 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • CKD stages 3 or 4 (estimated glomerular filtration rate (eGFR) between 15 and 59)

  • Diagnosis of secondary hyperparathyroidism, which is defined as:

    • Elevated intact PTH (iPTH) as per KDIGO guidelines:

      • CKD stage 3 (eGFR 30-59) or CKD stage 4 (eGFR 15-29) with iPTH > Upper Limit of Normal for lab (6.8 pmol/L)
  • Presence of Coronary Artery Calcium (CAC > 0)
  • Subject will be able to complete the study, to the best of his/her knowledge

Exclusion Criteria:

  • iPTH >1500 pg/ml
  • Current or previous use of bisphosphonates
  • History of parathyroidectomy or anticipated parathyroidectomy
  • History of cinacalcet use
  • History of a solid organ transplant or scheduled date for transplant surgery
  • History of coronary revascularization (coronary artery bypass surgery or percutaneous intervention)
  • History of coronary artifact (e.g. pacemaker, intracardiac defibrillator, artificial valve or biventricular leads)
  • Active atrial fibrillation
  • Weight greater than 300 pounds (due to limitations of equipment)
  • HIV positive
  • Current pregnancy (although pregnancy is very rare in the CKD population)
  • Life expectancy less than two years as judged by primary physician
  • Institutionalized patients (nursing home or prisoners)
  • Language barrier or mental incapacity to consent
  • Inability to swallow tablets or current gastrointestinal disorder that may be associated with impaired absorption of orally administered medications.

Sites / Locations

  • Hospital of the University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Calcitriol

Paricalcitol

Arm Description

Calcitriol is a synthetic vitamin D analog which is active in the regulation of the absorption of calcium from the gastrointestinal tract and its utilization in the body. Calcitriol is available as capsules containing 0.25 mcg or 0.5 mcg calcitriol and as an oral solution containing 1 mcg/ml of calcitriol. All dosage forms contain butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) as antioxidants. Subjects taking calcitriol started at 0.25 mcg 3x/week and titrated up during the next visit according to PTH levels.

Paricalcitol, USP, the active ingredient in Zemplar® Capsules, is a synthetically manufactured analog of calcitriol, the metabolically active form of vitamin D indicated for the prevention and treatment of secondary hyperparathyroidism in chronic kidney disease. Zemplar is available as soft gelatin capsules for oral administration containing 1 mcg, 2 mcg or 4 mcg of paricalcitol. Each capsule also contains medium chain triglycerides, alcohol, and butylated hydroxytoluene. Subjects taking paricalcitol will be started at 2 mcg 3x/week and titrated up during the next visit according to PTH levels.

Outcomes

Primary Outcome Measures

Coronary Artery (CAC) Score Progression
coronary artery (CAC) score difference between baseline and followup CT scans. It was measured in Agatston units. These are units of amount of calcification in the blood vessels so it's a continuous variable. The amount of calcium was quantified with the Agatston scoring method. Calcium scores were adjusted with a standard calcium phantom that was scanned along with the participant. The phantom contained known calcium density bars and provided a way to calibrate the x-ray attenuation level. Participants scoring CAC >400 are considered to be at risk for having at least one coronary lesion.

Secondary Outcome Measures

Full Information

First Posted
September 11, 2008
Last Updated
December 7, 2017
Sponsor
Joslin Diabetes Center
Collaborators
Abbott
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1. Study Identification

Unique Protocol Identification Number
NCT00752102
Brief Title
Vitamin D and Coronary Calcification Study
Acronym
VCOR
Official Title
A Phase IV, Randomized, Single-center Study of the Effects of Calcitriol and Paricalcitol on Vascular Calcification in Chronic Kidney Disease Stages 3 and 4
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
September 2008 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
October 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Joslin Diabetes Center
Collaborators
Abbott

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Patients with chronic kidney disease (CKD) have a higher mortality rate than the general population, with cardiovascular disease (CVD) accounting for approximately 50% of deaths. Vascular calcification is a common finding in patients with CKD. Furthermore, patients with CKD develop secondary hyperparathyroidism, partly because of a decrease of calcitriol synthesis on the kidney. Treatment of secondary hyperparathyroidism includes use of activated vitamin D including calcitriol and paricalcitol. Recent evidence in dialysis patients suggest an improved survival in patients using paricalcitol compared to calcitriol. Studies in uremic rats suggests that there are differential effects of calcitriol and paricalcitol in expression of markers of soft-tissue calcification independent of calcium-phosphorus product. Calcitriol increased calcification of vascular smooth muscle cells cultured in calcification media. There was also significant increase in pulse pressure in animals treated with calcitriol. The investigators hypothesize that these different forms of vitamin D may have differential effects in vascular calcification progression in CKD patients.
Detailed Description
Coronary artery calcification (CAC) is a risk marker for CVD and mortality. In animal models, calcitriol significantly increased the serum calcium-phosphate product and aortic calcium content, while paricalcitol had no effect. The objective of this randomized, blinded single-center is to determine the differential effect of oral calcitriol and paracalcitol on vascular calcification in patients with chronic kidney disease (CKD). We performed a total of 89 screening visits and randomized 44 participants. Forty participants completed the final visit. Diagram 1 presents the recruitment schematic.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Disease, Vitamin D Deficiency, Coronary Calcification, Disorders of Calcium and Bone Metabolism
Keywords
Secondary Hyperparathryoidism, Chronic Kidney Disease, Vitamin D, Coronary Calcification, Bone metabolism

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Calcitriol
Arm Type
Active Comparator
Arm Description
Calcitriol is a synthetic vitamin D analog which is active in the regulation of the absorption of calcium from the gastrointestinal tract and its utilization in the body. Calcitriol is available as capsules containing 0.25 mcg or 0.5 mcg calcitriol and as an oral solution containing 1 mcg/ml of calcitriol. All dosage forms contain butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) as antioxidants. Subjects taking calcitriol started at 0.25 mcg 3x/week and titrated up during the next visit according to PTH levels.
Arm Title
Paricalcitol
Arm Type
Active Comparator
Arm Description
Paricalcitol, USP, the active ingredient in Zemplar® Capsules, is a synthetically manufactured analog of calcitriol, the metabolically active form of vitamin D indicated for the prevention and treatment of secondary hyperparathyroidism in chronic kidney disease. Zemplar is available as soft gelatin capsules for oral administration containing 1 mcg, 2 mcg or 4 mcg of paricalcitol. Each capsule also contains medium chain triglycerides, alcohol, and butylated hydroxytoluene. Subjects taking paricalcitol will be started at 2 mcg 3x/week and titrated up during the next visit according to PTH levels.
Intervention Type
Drug
Intervention Name(s)
Calcitriol (Rocaltrol®)
Other Intervention Name(s)
Calcijex®, Rocaltrol®
Intervention Description
Subjects taking calcitriol will be started at 0.25 mcg 3x/week and titrated up during the next visit according to PTH levels. If at the 12 week visit, PTH is still not at goal, then calcitriol will be increased to 0.5 mcg 3x/week.
Intervention Type
Drug
Intervention Name(s)
Paricalcitol
Other Intervention Name(s)
Zemplar®
Intervention Description
Subjects taking paricalcitol will be started at 2 mcg 3x/week and titrated up during the next visit according to PTH levels. If at the 12 week visit, PTH is still not at goal, then paricalcitol will be increased to 4 mcg 3x/week.
Primary Outcome Measure Information:
Title
Coronary Artery (CAC) Score Progression
Description
coronary artery (CAC) score difference between baseline and followup CT scans. It was measured in Agatston units. These are units of amount of calcification in the blood vessels so it's a continuous variable. The amount of calcium was quantified with the Agatston scoring method. Calcium scores were adjusted with a standard calcium phantom that was scanned along with the participant. The phantom contained known calcium density bars and provided a way to calibrate the x-ray attenuation level. Participants scoring CAC >400 are considered to be at risk for having at least one coronary lesion.
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: CKD stages 3 or 4 (estimated glomerular filtration rate (eGFR) between 15 and 59) Diagnosis of secondary hyperparathyroidism, which is defined as: Elevated intact PTH (iPTH) as per KDIGO guidelines: CKD stage 3 (eGFR 30-59) or CKD stage 4 (eGFR 15-29) with iPTH > Upper Limit of Normal for lab (6.8 pmol/L) Presence of Coronary Artery Calcium (CAC > 0) Subject will be able to complete the study, to the best of his/her knowledge Exclusion Criteria: iPTH >1500 pg/ml Current or previous use of bisphosphonates History of parathyroidectomy or anticipated parathyroidectomy History of cinacalcet use History of a solid organ transplant or scheduled date for transplant surgery History of coronary revascularization (coronary artery bypass surgery or percutaneous intervention) History of coronary artifact (e.g. pacemaker, intracardiac defibrillator, artificial valve or biventricular leads) Active atrial fibrillation Weight greater than 300 pounds (due to limitations of equipment) HIV positive Current pregnancy (although pregnancy is very rare in the CKD population) Life expectancy less than two years as judged by primary physician Institutionalized patients (nursing home or prisoners) Language barrier or mental incapacity to consent Inability to swallow tablets or current gastrointestinal disorder that may be associated with impaired absorption of orally administered medications.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sylvia E Rosas, MD, MSCE
Organizational Affiliation
Joslin Diabetes Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
32775985
Citation
Anis KH, Pober D, Rosas SE. Vitamin D Analogues and Coronary Calcification in CKD Stages 3 and 4: A Randomized Controlled Trial of Calcitriol Versus Paricalcitol. Kidney Med. 2020 Jun 17;2(4):450-458. doi: 10.1016/j.xkme.2020.05.009. eCollection 2020 Jul-Aug.
Results Reference
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Vitamin D and Coronary Calcification Study

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