Vitamin D and Coronary Calcification Study - Full Text View

Sponsors and Collaborators:	University of Pennsylvania Abbott
Information provided by:	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 Coronary Calcification Bone Metabolism	Drug: Calcitriol (Rocaltrol®) Drug: Paricalcitol	Phase IV

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy 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

Resource links provided by NLM:

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:	October 2011
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Calcitriol: Active Comparator	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.
Paricalcitol: Active Comparator	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.

Eligibility

Ages Eligible for Study:	35 Years to 74 Years
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 NKF guidelines:
  - CKD stage 3 (eGFR 30-59) with iPTH >7.7 pmol/L (70 pg/ml), calcium <9.5, and phosphorus <4.6
  - CKD stage 4 (eGFR 15-29) with iPTH >12.1 pmol/L (110 pg/ml)
CAC score >10
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 myocardial infarction
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: Katharine Schankel	215-615-3848	katharine.schankel@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 ( Sylvia E. Rosas, MD, MSCE )
Study ID Numbers:	Abbott #20128
Study First Received:	September 11, 2008
Last Updated:	March 25, 2009
ClinicalTrials.gov Identifier:	NCT00752102 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Pennsylvania:

Chronic Kidney Disease
Vitamin D
Coronary Calcification
Bone metabolism

Study placed in the following topic categories:

Renal Insufficiency
Metabolic Diseases
Kidney Failure, Chronic
Bone Density Conservation Agents
Trace Elements
Cardiovascular Agents
Calcitriol
Calcinosis
Calcium, Dietary

Vitamin D
Urologic Diseases
Renal Insufficiency, Chronic
Vitamins
Vasoconstrictor Agents
Micronutrients
Kidney Diseases
Metabolic Disorder
Kidney Failure

Additional relevant MeSH terms:

Renal Insufficiency
Metabolic Diseases
Molecular Mechanisms of Pharmacological Action
Growth Substances
Calcium Channel Agonists
Physiological Effects of Drugs
Kidney Failure, Chronic
Bone Density Conservation Agents
Cardiovascular Agents
Pharmacologic Actions
Calcitriol

Membrane Transport Modulators
Calcinosis
Calcium Metabolism Disorders
Urologic Diseases
Renal Insufficiency, Chronic
Therapeutic Uses
Vitamins
Vasoconstrictor Agents
Kidney Diseases
Micronutrients
Kidney Failure

ClinicalTrials.gov processed this record on September 02, 2009