Paricalcitol and Endothelial Function in Chronic Kidney Disease Patients (the PENNY Study) - Full Text View

Purpose

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).

Condition	Intervention	Phase
Chronic Kidney Disease.	Drug: Paracalcitol Drug: placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Effect of Paricalcitol on Endothelial Function in Chronic Kidney Disease (CKD) Patients (the PENNY Study)

Resource links provided by NLM:

MedlinePlus related topics: Chronic Kidney Disease Vitamin D

Drug Information available for: Vitamin D Paricalcitol

U.S. FDA Resources

Further study details as provided by Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy:

Primary Outcome Measures:

Endothelial function measurement [ Time Frame: 12 weeks from baseline ] [ Designated as safety issue: No ]
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 Outcome Measures:

Endothelial function and plasma/serum and genetic biomarkers of bone mineral disorders in CKD (BMD-CKD) and renin angiotensin-aldosteron system (RAS). [ Time Frame: 12 weeks from baseline ] [ Designated as safety issue: No ]
The investigators will analyze 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).

Enrollment:	88
Study Start Date:	June 2011
Study Completion Date:	August 2012
Primary Completion Date:	August 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo Placebo capsules daily for 12 weeks.	Drug: placebo
Experimental: Paracalcitol see "Intervention description" for details.	Drug: Paracalcitol Patients in the experimental arm received 2 micrograms Paricalcitol capsules daily, for 12 weeks. This dose was adjusted based on clinical laboratory parameters and the maximum dose was 2 micrograms daily. Other Name: Active form of Vitamin D.

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Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01680198

Locations

Italy
Nephrology, Dialysis and Transplantation Unit
Reggio Calabria, Italy, 89124

Sponsors and Collaborators

Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy

Investigators

Study Director:

Giuseppe Curatola, MD

Nephrology, Dialysis and Transplantation Unit

More Information

Publications:

Yilmaz MI, Sonmez A, Saglam M, Yaman H, Kilic S, Demirkaya E, Eyileten T, Caglar K, Oguz Y, Vural A, Yenicesu M, Zoccali C. FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease. Kidney Int. 2010 Oct;78(7):679-85. Epub 2010 Jul 7.

London GM, Guérin AP, Verbeke FH, Pannier B, Boutouyrie P, Marchais SJ, Mëtivier F. Mineral metabolism and arterial functions in end-stage renal disease: potential role of 25-hydroxyvitamin D deficiency. J Am Soc Nephrol. 2007 Feb;18(2):613-20. Epub 2007 Jan 3.

Yamamoto T, Kozawa O, Tanabe K, Akamatsu S, Matsuno H, Dohi S, Hirose H, Uematsu T. 1,25-dihydroxyvitamin D3 stimulates vascular endothelial growth factor release in aortic smooth muscle cells: role of p38 mitogen-activated protein kinase. Arch Biochem Biophys. 2002 Feb 1;398(1):1-6.

Wakasugi M, Noguchi T, Inoue M, Kazama Y, Tawata M, Kanemaru Y, Onaya T. Vitamin D3 stimulates the production of prostacyclin by vascular smooth muscle cells. Prostaglandins. 1991 Aug;42(2):127-36.

Teng M, Wolf M, Ofsthun MN, Lazarus JM, Hernán MA, Camargo CA Jr, Thadhani R. Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol. 2005 Apr;16(4):1115-25. Epub 2005 Feb 23.

Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med. 2003 Jul 31;349(5):446-56.

Ravani P, Malberti F, Tripepi G, Pecchini P, Cutrupi S, Pizzini P, Mallamaci F, Zoccali C. Vitamin D levels and patient outcome in chronic kidney disease. Kidney Int. 2009 Jan;75(1):88-95. Epub 2008 Oct 8.

Testa A, Mallamaci F, Benedetto FA, Pisano A, Tripepi G, Malatino L, Thadhani R, Zoccali C. Vitamin D receptor (VDR) gene polymorphism is associated with left ventricular (LV) mass and predicts left ventricular hypertrophy (LVH) progression in end-stage renal disease (ESRD) patients. J Bone Miner Res. 2010 Feb;25(2):313-9.

Ghiadoni L, Faita F, Salvetti M, Cordiano C, Biggi A, Puato M, Di Monaco A, De Siati L, Volpe M, Ambrosio G, Gemignani V, Muiesan ML, Taddei S, Lanza GA, Cosentino F. Assessment of flow-mediated dilation reproducibility: a nationwide multicenter study. J Hypertens. 2012 Jul;30(7):1399-405.

Responsible Party:	Carmine Zoccali, Prof., National Research Council, Italy
ClinicalTrials.gov Identifier:	NCT01680198 History of Changes
Other Study ID Numbers:	Oct2010PENNYStudy
Study First Received:	August 30, 2012
Last Updated:	October 1, 2012
Health Authority:	Italy: National Institute of Health

Keywords provided by Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy:

Vitamin D
Paracalcitol
Chronic kidney disease
Endothelial dysfunction
Flow mediated vasodilation

Additional relevant MeSH terms:

Kidney Diseases
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency
Vitamin D

Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on June 18, 2013