Vitamin D and Coronary Calcification Study - Full Text View

Sponsor:	University of Pennsylvania
Collaborator:	Abbott
Information provided by (Responsible Party):	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT00752102

Purpose

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.

Condition	Intervention	Phase
Chronic Kidney Disease Vitamin D Deficiency Coronary Calcification Disorders of Calcium and Bone Metabolism	Drug: Calcitriol (Rocaltrol®) Drug: Paricalcitol	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
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

Resource links provided by NLM:

Genetics Home Reference related topics: carbamoyl phosphate synthetase I deficiency

MedlinePlus related topics: Calcium Kidney Failure Vitamin D

Drug Information available for: Calcitriol 19-Nor-1alpha,25-dihydroxyvitamin D2 Vitamin D

U.S. FDA Resources

Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:

To determine prospectively if there is a differential effect on coronary artery (CAC) score progression between calcitriol and paricalcitol in patients with chronic kidney disease. [ Time Frame: Baseline and week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine prospectively if there is a differential effect on aortic and valvular score progression and arterial stiffness in patients with chronic kidney disease receiving calcitriol and paricalcitol. [ Time Frame: Baseline and week 48 ] [ Designated as safety issue: No ]
To determine prospectively if there is a differential effect on biomarkers of vascular calcification and mineral metabolism in patients with chronic kidney disease receiving calcitriol and paricalcitol. [ Time Frame: Baseline and week 48 ] [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	September 2008
Estimated Study Completion Date:	January 2013
Estimated Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Calcitriol	Drug: 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. Other Names: Calcijex® Rocaltrol®
Active Comparator: Paricalcitol	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. Other Name: Zemplar®

Eligibility

Ages Eligible for Study:	25 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00752102

Contacts

Contact: Philip T Cochetti	215-615-3848	philip.cochetti@uphs.upenn.edu
Contact: Christine Bonney	215-615-3848	christine.bonney@uphs.upenn.edu

Locations

United States, Pennsylvania
Hospital of the University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19107
Principal Investigator: Sylvia E Rosas, MD, MSCE

Sponsors and Collaborators

University of Pennsylvania

Abbott

Investigators

Principal Investigator:

Sylvia E Rosas, MD, MSCE

University of Pennsylvania

More Information

No publications provided

Responsible Party:	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT00752102 History of Changes
Other Study ID Numbers:	Abbott #20128
Study First Received:	September 11, 2008
Last Updated:	November 14, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Pennsylvania:

Secondary Hyperparathryoidism
Chronic Kidney Disease
Vitamin D
Coronary Calcification
Bone metabolism

Additional relevant MeSH terms:

Calcinosis
Kidney Diseases
Kidney Failure, Chronic
Renal Insufficiency, Chronic
Vitamin D Deficiency
Calcium Metabolism Disorders
Metabolic Diseases
Urologic Diseases
Renal Insufficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Calcitriol

Vitamin D
Vitamins
Ergocalciferols
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Calcium Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012