Effect of Paricalcitol on Endothelial Function in Chronic Kidney Disease (CKD) Patients (the PENNY Study)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 88
- Locations
- 1
- Primary Endpoint
- Endothelial function measurement
Study Overview
Brief Summary
The primary aim of this study was to test the hypothesis that Paricalcitol, an active form of vitamin D, improved endothelial function in stage 3-4 chronic kidney disease (CKD) patients. A secondary aim of this trial was to study the relationship between endothelial function and plasma/serum and genetic biomarkers of bone mineral disorders in CKD (BMD-CKD) and renin angiotensin-aldosteron system (RAS) (angiotensin II and plasma renin activity).
Detailed Description
Primary objective: Test the hypothesis that Paricalcitol, an active form of vitamin D improves endothelial function in stage 3-4 chronic kidney disease (CKD) patients.
Secondary analysis: Study the relationship between endothelial function and plasma/serum and genetic biomarkers of bone mineral disorders in CKD (BMD-CKD) and renin angiotensin-aldosteron system (RAS) (angiotensin II and plasma renin activity).
Background:
Endothelial function is altered in patients with CKD. Factors responsible for disturbed endothelium-dependent vasodilatation in CKD include reduced bioactivity of the nitric oxide (NO) pathway with decreased endothelial NO synthase (NOS) activity or inhibition via accumulation of endogenous inhibitors. In patients with CKD and in those on dialysis serum 25(OH)D3 and 1,25(OH)2D3 levels are associated with FMD. Vitamin D receptors and 1 -hydroxylase activity are present in endothelial and vascular smooth muscle cells and 1,25(OH)2D3 stimulates vascular endothelial growth factor and prostacyclin production by vascular smooth muscle cells. These biological observations may have clinical implications because paricalcitol treatment predicts longer survival in ESRD patients and very recent data link vitamin D to progression to ESRD in patients with stage 3-5 CKD. Furthermore, a previous study by us has shown that the BMSI polymorphism of the vitamin D receptor gene is associated with LVH and LVH progression in ESRD patients.
Study population: Patients with stage 3-4 CKD of both sexes in the age range 18-80 years. Patients taking vitamin D supplements, with abnormal liver function tests, symptomatic cardiovascular disease, diabetes or cancer and those whose medications changed during the study were excluded.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with iPTH level > 65 pg/ml; Ca between 8.4- 10.00 mg/dL and P between 2.9-4.5
- •Negative serum pregnancy test for female subjects of childbering potential.
- •Informed consent.
Exclusion Criteria
- •Use vitamin D supplements.
- •Altered liver function tests (bilirubin, aminotransferases and total alkaline phosphatase > 3 times the upper limit of normal ranges).
- •Sympthomatic cardiovascular disease on the basis of clinical history. Cancer.
Arms & Interventions
Placebo
Placebo capsules daily for 12 weeks.
Intervention: placebo (Drug)
Paracalcitol
see "Intervention description" for details.
Intervention: Paracalcitol (Drug)
Outcomes
Primary Outcomes
Endothelial function measurement
Time Frame: 12 weeks from baseline
Endothelial-dependent and independent vasodilation was assessed by a Toshiba Nemia XG Echo-Doppler applying a 7.5 MHz transducer that was fixed by an adjustable stereotactic clamp to warrant image stability. After baseline recording (1 min) a standard sphygmomanometer was placed on the right forearm 2 cm below the elbow and the cuff was inflated to 250 mmHg for 5 min. Recordings were performed during the 4 min following cuff deflation to estimate endothelium-dependent FMD. In studies of endothelium-independent vasodilatation recording times were 1 min for the baseline assessment and 5 min for changes in arterial diameter brought about by GTN. An interval of at least 1h was set between the last FMD assessment and GTN administration. All scans were recorded, stored and analyzed off-line. FMD and GTN were computed as the maximal % increase in diameter over baseline by an automatic edge detection system.
Secondary Outcomes
- Endothelial function and plasma/serum and genetic biomarkers of bone mineral disorders in CKD (BMD-CKD) and renin angiotensin-aldosteron system (RAS).(12 weeks from baseline)
Investigators
Carmine Zoccali
Prof.
Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy