Clinical trial NCT02598635: Effects of Cholecalciferol on Osteoprotegerin Levels in Patients on Peritoneal Dialysis
Official title: Effects of Cholecalciferol on Osteoprotegerin Levels and Other Clinical Outcomes in Chronic Kidney Disease Patients on Peritoneal Dialysis: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Vitamin D Deficiency
Vascular Calcification
Renal Insufficiency
End Stage Renal Failure on Dialysis
Keywords: Cholecalciferol
peritoneal dialysis
FGF23
Calcium
Phosphorus
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
First posted: 2015-11-06
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Relative reduction in serum osteoprotegerin (OPG) levels assessed by ELISA (in pg/mL) between study inclusion, and the 16-week intervention period.
timeFrame: 16 weeks
Secondary outcomes:
measure: Relative reduction in circulating intact fibroblast growth factor 23 (FGF23) levels (in pg/mL)
timeFrame: 16 weeks
measure: Relative reduction in circulating osteopontin (OPN) levels (in pg/mL)
timeFrame: 16 weeks
measure: Relative reduction in circulating osteocalcin (OCN) levels (in pg/mL)
timeFrame: 16 weeks
measure: 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.
timeFrame: 52 weeks
measure: Number of participants with courses of corrected calcium (>10.5 mg/dL) and phosphorus (>7 mg/dL) levels
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Mexico
country: Mexico
facility: National Medical Science and Nutrition Institute Salvador Zubiran MEXICO
state: Mexico city
Study officials:
affiliation: Head Dept Nephrology and Mineral Metabolism National Medical Science and Nutrition Institute Salvador Zubiran MEXICO
name: Ricardo Correa-Rotter, MD
role: STUDY_DIRECTOR
References:
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. Epub 2015 Aug 20.
citation: 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.
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):611-9. doi: 10.2215/CJN.06910714. Epub 2015 Mar 13.
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. Epub 2008 Oct 9.
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. doi: 10.20452/pamw.1678. Epub 2013 Mar 26.