Effects of Cholecalciferol on Osteoprotegerin Levels in Patients on Peritoneal Dialysis

Vitamin D Deficiency Clinical Trial

Official title:

Effects of Cholecalciferol on Osteoprotegerin Levels and Other Clinical Outcomes in Chronic Kidney Disease Patients on Peritoneal Dialysis: a Randomized Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02598635
• Other study ID #: 1419
• Status: Active, not recruiting
• Phase: Phase 4
• First received: October 31, 2015
• Last updated: March 22, 2017
• Start date: October 2015
• Est. completion date: June 2017

Study information

• Verified date: March 2017
• Source: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Aim: To investigate whether cholecalciferol (4800 U/daily) or placebo for 16 weeks reduces proteins levels associated with vascular calcification (osteoprotegerin, osteopontin, osteocalcin) in patients treated with peritoneal dialysis and 25(OH) vitamin D deficiency.

Description:

Patients with chronic kidney disease on peritoneal dialysis have very low 25-(OH) vitamin D levels. Vitamin D deficiency may be involved in generalized atherosclerosis, vascular calcification and cardiovascular mortality. Among others, Osteoprotegerin (OPG) has been implicated in the pathogenesis leading up vessel calcification in this patients. Furthermore, very low levels of 25-(OH) vitamin D in peritoneal dialysis patients are associated with increased levels of OPG and high values of vascular calcification scores in x-rays.

It is unknown whether cholecalciferol supplementation in patients on peritoneal dialysis with low levels of 25-(OH) vitamin D could change the proteins associated with vascular calcification.

The objective is to conduct a randomized, double-blind, placebo-controlled study focusing on the impact of Cholecalciferol substitution in 25-OH vitamin D deficient peritoneal dialysis patients on circulating OPG and other osteogenic biomarkers levels during 16 weeks of intervention.

Moreover, the impact of cholecalciferol on serum calcium and phosphorus levels, Kidney Disease Quality of Life Short Form, and ultrasound characteristics of carotid arterial will be performed during the first four weeks after inclusion, and after 28 weeks postintervention.

Peritoneal dialysis patients found to have 25-(OH) vitamin D levels <20 ng/ml will be included and will be randomized to receive either oral cholecalciferol therapy or placebo. Cholecalciferol will be administered at a daily dose of 4800 IU over a time period of 16 weeks.

All in all, 58 subjects will be included in this study.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 58
• Est. completion date: June 2017
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Peritoneal dialysis treatment for at least 3 months.

• Concentrations of 25-oh vitamin D <20 ng / mL

• Corrected calcium <10.5 mg / dL

• Serum phosphorus <7.0 mg / dL

• Intact parathyroid hormone > 50 pg / mL and <1500 pg/mL

Exclusion Criteria:

• Active participation in another protocol.

• Vitamin D deficiency due to a hereditary disease or liver disease.

• Use of cholecalciferol = 2000 IU per day within 6 months prior

• New prescription of calcitriol or paricalcitol at any dose within three months prior to the intervention (The subjects may be taking calcitriol or paricalcitol only if these drugs are taken at least three months before and no substantial changes in dosage have been made).

• Use of bisphosphonates.

• Treatment with anticonvulsants or other drugs that affect the metabolism of vitamin D.

• Pregnancy and lactation.

• Active cancer or other active inflammatory disease.

• HIV or AIDS

Related Conditions & MeSH terms

• Calcinosis
• End Stage Renal Failure on Dialysis
• Kidney Failure, Chronic
• Renal Insufficiency
• Renal Insufficiency, Chronic
• Vascular Calcification
• Vitamin D Deficiency

Intervention

Drug:
• Cholecalciferol
Patients on peritoneal dialysis and 25-(OH) levels <20 ng/mL will received one capsule of cholecalciferol (4800 U) once a day for 16 weeks.
• Placebo
An oral placebo capsule matching Cholecalciferol in terms of appearance, smell and taste will be administered once a day for 16 weeks.

Locations

Country	Name	City	State
Mexico	National Medical Science and Nutrition Institute Salvador Zubiran MEXICO	Mexico	Mexico city

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Country where clinical trial is conducted

Mexico, 

References & Publications (5)

Ammirati AL, Dalboni MA, Cendoroglo M, Draibe SA, Santos RD, Miname M, Canziani ME. The progression and impact of vascular calcification in peritoneal dialysis patients. Perit Dial Int. 2007 May-Jun;27(3):340-6. — View Citation

Bhan I, Dobens D, Tamez H, Deferio JJ, Li YC, Warren HS, Ankers E, Wenger J, Tucker JK, Trottier C, Pathan F, Kalim S, Nigwekar SU, Thadhani R. Nutritional vitamin D supplementation in dialysis: a randomized trial. Clin J Am Soc Nephrol. 2015 Apr 7;10(4): — View Citation

Janda K, Krzanowski M, Chowaniec E, Kusnierz-Cabala B, Dumnicka P, Krasniak A, Podolec P, Sulowicz W. Osteoprotegerin as a marker of cardiovascular risk in patients on peritoneal dialysis. Pol Arch Med Wewn. 2013;123(4):149-55. — View Citation

Ramirez-Sandoval JC, Casanova I, Villar A, Gomez FE, Cruz C, Correa-Rotter R. Biomarkers Associated with Vascular Calcification in Peritoneal Dialysis. Perit Dial Int. 2016 May-Jun;36(3):262-8. doi: 10.3747/pdi.2014.00250. — View Citation

Van Campenhout A, Golledge J. Osteoprotegerin, vascular calcification and atherosclerosis. Atherosclerosis. 2009 Jun;204(2):321-9. doi: 10.1016/j.atherosclerosis.2008.09.033. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative reduction in serum osteoprotegerin (OPG) levels assessed by ELISA (in pg/mL) between study inclusion, and the 16-week intervention period.	The concentrations of OPG will be assessed using ELISA (Austin, Texas, USA) at inclusion and after 16 weeks of treatment with cholecalciferol or placebo.Minimum detectable concentrations for OPG are 1.9 pg/mL; intra and inter-assay coefficients of variability are 5% and 11% for OPG.	16 weeks
Secondary	Relative reduction in circulating intact fibroblast growth factor 23 (FGF23) levels (in pg/mL)	The concentrations of intact FGF-23 will be assessed using ELISA (Austin, Texas, USA)	16 weeks
Secondary	Relative reduction in circulating osteopontin (OPN) levels (in pg/mL)	The concentrations of OPN will be assessed using ELISA (Austin, Texas, USA)	16 weeks
Secondary	Relative reduction in circulating osteocalcin (OCN) levels (in pg/mL)	The concentrations of OCN will be assessed using ELISA ( Austin, Texas, USA)	16 weeks
Secondary	Relative reduction in intima-media thickness measurements in the carotid artery. Ultrasound examination will be performed at study inclusion, at 16 weeks after inclusion, and up to 52 weeks post inclusion.	Ultrasound examination will be performed with the use of an 8-megahertz annular array ultrasound imaging system by a single trained sonographer. With this technique, 2 parallel echogenic lines separated by an anechoic space can be visualized at levels of the artery wall. The distance between the 2 lines gives a reliable index of the thickness of the intimal-medial complex. Subjects will be examined in the supine position. Ultrasound scans of the right and left last distal centimeter of common carotid arteries and bifurcation and of the first proximal centimeter of internal carotid arteries in 3 different projections (anterior, lateral, and posterior) will be performed. All measurements will be made at the time of scanning on unfrozen images of longitudinal scans by using the machine's electronic caliper.	52 weeks
Secondary	Number of participants with courses of corrected calcium (>10.5 mg/dL) and phosphorus (>7 mg/dL) levels	During follow-up, all participants will be interviewed. All participants will be interviewed and a blood sample will be taken every 4-6 weeks.	16 weeks