Effects of Cholecalciferol on Osteoprotegerin Levels in Patients on Peritoneal Dialysis

March 22, 2017 updated by: Juan C Ramirez-Sandoval, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

58

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • Mexico city
      • Mexico, Mexico city, Mexico, 01400
        • National Medical Science and Nutrition Institute Salvador Zubiran MEXICO

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cholecalciferol
A capsule of pulverized cholecalciferol 4800 U will be administered once a day for 16 weeks. At serum calcium levels > 10.5 mg/dL (2.65 mmol/l) and/or at serum phosphorus levels > 7 mg/dL (2.26 mmol/L) capsule administration will be discontinued and restarted one month after when serum calcium levels or phosphorus levels declined to < 10.6 mg/dL and/or <7.1 mg/dL respectively.
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.
Other Names:
  • "Valmetrol-3"
Placebo Comparator: Placebo
An oral placebo capsule matching Cholecalciferol in terms of appearance, smell and taste will be administered once a day for 16 weeks. At serum calcium levels > 10.5 mg/dL (2.65 mmol/l) and/or at serum phosphorus levels > 7 mg/dL (2.26 mmol/L) capsule administration will be discontinued and restarted one month after when serum calcium levels or phosphorus levels declined to < 10.6 mg/dL and/or <7.1 mg/dL respectively.
Drug: Placebo
An oral placebo capsule matching Cholecalciferol in terms of appearance, smell and taste will be administered once a day for 16 weeks.
Other Names:
  • (Capsule similar to Cholecalciferol)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relative reduction in serum osteoprotegerin (OPG) levels assessed by ELISA (in pg/mL) between study inclusion, and the 16-week intervention period.
Time Frame: 16 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relative reduction in circulating intact fibroblast growth factor 23 (FGF23) levels (in pg/mL)
Time Frame: 16 weeks
The concentrations of intact FGF-23 will be assessed using ELISA (Austin, Texas, USA)
16 weeks
Relative reduction in circulating osteopontin (OPN) levels (in pg/mL)
Time Frame: 16 weeks
The concentrations of OPN will be assessed using ELISA (Austin, Texas, USA)
16 weeks
Relative reduction in circulating osteocalcin (OCN) levels (in pg/mL)
Time Frame: 16 weeks
The concentrations of OCN will be assessed using ELISA ( Austin, Texas, USA)
16 weeks
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.
Time Frame: 52 weeks
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
Number of participants with courses of corrected calcium (>10.5 mg/dL) and phosphorus (>7 mg/dL) levels
Time Frame: 16 weeks
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Investigators

  • Study Director: Ricardo Correa-Rotter, MD, Head Dept Nephrology and Mineral Metabolism National Medical Science and Nutrition Institute Salvador Zubiran MEXICO

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2015

Primary Completion (Actual)

October 1, 2016

Study Completion (Anticipated)

June 1, 2017

Study Registration Dates

First Submitted

October 31, 2015

First Submitted That Met QC Criteria

November 5, 2015

First Posted (Estimate)

November 6, 2015

Study Record Updates

Last Update Posted (Actual)

March 24, 2017

Last Update Submitted That Met QC Criteria

March 22, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1419

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Renal Insufficiency

Clinical Trials on Cholecalciferol

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mauritius

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe