Clinical trial NCT00752102: Vitamin D and Coronary Calcification Study
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
Overall status: COMPLETED
Phase: PHASE4
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
Lead sponsor: Joslin Diabetes Center
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2008-09-15
Enrollment: 44
Sex: ALL
Minimum age (years): 25
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Coronary Artery (CAC) Score Progression
timeFrame: 48 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Joslin Diabetes Center
name: Sylvia E Rosas, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
References:
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.