Vitamin D and Coronary Calcification Study

NCT ID: NCT00752102

Last Updated: 2017-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2013-10-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Calcitriol

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.

Group Type: ACTIVE_COMPARATOR

Calcitriol (Rocaltrol®)

Intervention Type: DRUG

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.

Paricalcitol

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.

Group Type: ACTIVE_COMPARATOR

Paricalcitol

Intervention Type: DRUG

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.

Interventions

Calcitriol (Rocaltrol®)

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

Paricalcitol

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.

Intervention Type: DRUG

Other Intervention Names

Calcijex®; Rocaltrol®; Zemplar®

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.

• Minimum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abbott

INDUSTRY

Sponsor Role: collaborator

Joslin Diabetes Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sylvia E Rosas, MD, MSCE

Role: PRINCIPAL_INVESTIGATOR

Joslin Diabetes Center

Locations

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32775985 (View on PubMed)

Other Identifiers

Abbott #20128

Identifier Type: -

Identifier Source: org_study_id