NCT01680198

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
88

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Jun 2011

Shorter than P25 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2011

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2012

Completed
29 days until next milestone

First Submitted

Initial submission to the registry

August 30, 2012

Completed
8 days until next milestone

First Posted

Study publicly available on registry

September 7, 2012

Completed
Last Updated

October 2, 2012

Status Verified

October 1, 2012

Enrollment Period

1.2 years

First QC Date

August 30, 2012

Last Update Submit

October 1, 2012

Conditions

Chronic Kidney Disease.

Keywords

Vitamin DParacalcitolChronic kidney diseaseEndothelial dysfunctionFlow mediated vasodilation

Outcome Measures

Primary Outcomes (1)

  • Endothelial function measurement

    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.

    12 weeks from baseline

Secondary Outcomes (1)

  • 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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo capsules daily for 12 weeks.

Drug: placebo

Paracalcitol

EXPERIMENTAL

see "Intervention description" for details.

Drug: Paracalcitol

Interventions

ParacalcitolDRUG

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.

Also known as: Active form of Vitamin D.
Paracalcitol
placeboDRUG
Placebo

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Nephrology, Dialysis and Transplantation Unit

Reggio Calabria, Reggio Calabria, 89124, Italy

Location

Related Publications (13)

  • 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. doi: 10.1038/ki.2010.194. Epub 2010 Jul 7.

    PMID: 20613714BACKGROUND

  • London GM, Guerin AP, Verbeke FH, Pannier B, Boutouyrie P, Marchais SJ, Metivier 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. doi: 10.1681/ASN.2006060573. Epub 2007 Jan 3.

    PMID: 17202417BACKGROUND

  • 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. doi: 10.1006/abbi.2001.2632.

    PMID: 11811942BACKGROUND

  • 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. doi: 10.1016/0090-6980(91)90072-n.

    PMID: 1775635BACKGROUND

  • Teng M, Wolf M, Ofsthun MN, Lazarus JM, Hernan 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. doi: 10.1681/ASN.2004070573. Epub 2005 Feb 23.

    PMID: 15728786BACKGROUND

  • 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. doi: 10.1056/NEJMoa022536.

    PMID: 12890843BACKGROUND

  • 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. doi: 10.1038/ki.2008.501. Epub 2008 Oct 8.

    PMID: 18843258BACKGROUND

  • 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. doi: 10.1359/jbmr.090717.

    PMID: 20422622BACKGROUND

  • 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. doi: 10.1097/HJH.0b013e328353f222.

    PMID: 22525207BACKGROUND

  • D'arrigo G, Pizzini P, Cutrupi S, Tripepi R, Tripepi G, Mallamaci F, Zoccali C. Vitamin D receptor activation raises soluble thrombomodulin levels in chronic kidney disease patients: a double blind, randomized trial. Nephrol Dial Transplant. 2019 May 1;34(5):819-824. doi: 10.1093/ndt/gfy085.

    PMID: 29668990DERIVED

  • Torino C, Pizzini P, Cutrupi S, Tripepi R, Vilasi A, Tripepi G, Mallamaci F, Zoccali C. Effect of Vitamin D Receptor Activation on the AGE/RAGE System and Myeloperoxidase in Chronic Kidney Disease Patients. Oxid Med Cell Longev. 2017;2017:2801324. doi: 10.1155/2017/2801324. Epub 2017 Dec 6.

    PMID: 29362665DERIVED

  • Spoto B, Pizzini P, Tripepi G, Mallamaci F, Zoccali C. Circulating adiponectin modifies the FGF23 response to vitamin D receptor activation: a post hoc analysis of a double-blind, randomized clinical trial. Nephrol Dial Transplant. 2018 Oct 1;33(10):1764-1769. doi: 10.1093/ndt/gfx344.

    PMID: 29304245DERIVED

  • Zoccali C, Curatola G, Panuccio V, Tripepi R, Pizzini P, Versace M, Bolignano D, Cutrupi S, Politi R, Tripepi G, Ghiadoni L, Thadhani R, Mallamaci F. Paricalcitol and endothelial function in chronic kidney disease trial. Hypertension. 2014 Nov;64(5):1005-11. doi: 10.1161/HYPERTENSIONAHA.114.03748. Epub 2014 Aug 4.

    PMID: 25259743DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Renal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Giuseppe Curatola, MD

    Nephrology, Dialysis and Transplantation Unit

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof.

Study Record Dates

First Submitted

August 30, 2012

First Posted

September 7, 2012

Study Start

June 1, 2011

Primary Completion

August 1, 2012

Study Completion

August 1, 2012

Last Updated

October 2, 2012

Record last verified: 2012-10

Locations

IT(1)