How Bone is Made in Children Receiving Dialysis

Regulation of Bone Mineralization in Renal Osteodystrophy

The study outlined is designed to measure and to determine whether the combined use of vitamin D2 (ergocalciferoI) and 1-alpha-hydroxyvitamin D2 (doxercalciferol)) or doxercalciferol alone will correct the mineralization defect in pediatric patients with established secondary hyperparathyroidism (2°HPT) undergoing regular peritoneal dialysis. Serum phosphorus levels will be controlled with a calcium¬-free-metal free phosphate binder; (obtained at baseline and after 8 months of treatment) sevelamer. Indices of bone mineralization obtained at baseline and after 8 months of treatment will be measured by quantitative histomorphometry in iliac crest bone biopsies after double tetracycline labeling. Immunohistochemistry will be done in specimens of bone biopsies from iliac crest to examine the expression for selected markers of bone turnover and mineralization such as FGF-23, DMP1, MEPE and OPG. Serum PTH levels will be measured with the 1st and 2nd generation immunometric assay (PTH-IMAs) and fibroblast growth factor-23 (FGF-23) will be determined by one assay with specific detection antibodies that are against epitopes within the C-terminus of FGF-23 and another assay that uses antibodies against epitopes within the N- and C-terminal portions of the molecule respectively. The value of non-invasive assessment of bone mass by quantitative computed tomography (QCT) and its relationship with vascular disease determined by ultrasound (US) of intimal carotid thickness (CIMT) will be correlated with bone histomorphometry and the different biochemical determinations.

Study Overview

• Status: Unknown
• Conditions: Bone Mineralization Defect
• Intervention / Treatment: Drug: Vitamin D2

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92354
      • Recruiting
      • Loma Linda University
      • Contact: Shobbha Sahney, MD; Phone Number: 909-558-8242; Email: ssahney@llu.edu
      • Principal Investigator: Shobha Sahney, MD
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Childrens Hospital Los Angeles
      • Contact: Kevin Lemley, MD; Phone Number: 323-361-2295; Email: klemley@chla.usc.edu
      • Principal Investigator: Kevin Lemley, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• medically stable patients
• 6-21 years old
• undergoing treatment with continuous cycling peritoneal dialysis
• evidence of mineralization defect and secondary hyperparathyroidism

Exclusion Criteria:

• histopathological lesion of bone such as adynamic bone or osteomalacia
• poor compliance
• current treatment with prednisone or other immunosuppressives
• treatment with human recombinant growth hormone
• parathyroidectomy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment with vitamin D2; Vitamin D2 50,000u titrated to serum 25(OH)D values given orally once a month in addition to standard of care: Doxercalciferol escalating doses beginning at 2.5 mcg given orally thrice weekly. Sevelamer Carbonate 800 mg (1600- 4800 mg) given orally with each meal	Drug: Vitamin D2; These patients will receive standard of care vitamin D 1,25 therapy with intervention of vitamin D2; Other Names: Ergocalciferol
No Intervention: Standard of Care; Standard of Care: Doxercalciferol escalating doses beginning at 2.5 mcg given orally thrice weekly. Sevelamer Carbonate 800 mg (1600- 4800 mg) given orally with each meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of bone mineralization defect demonstrated by bone histomorphometry	Iliac crest bone biopsy pre and post treatment with vitamin D2	8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic improvement of skeletal abnormalities associated with renal osteodystrophy	We will compare skeletal lesions identified through radiographic studies with bone histomorphometry pre and post treatment with vitamin D2	8 months

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Loma Linda University; Children's Hospital Los Angeles
• Investigators: Principal Investigator: Isidro Salusky, MD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Anticipated): June 1, 2014
• Study Completion (Anticipated): June 1, 2014

Study Registration Dates

• First Submitted: February 20, 2013
• First Submitted That Met QC Criteria: February 22, 2013
• First Posted (Estimate): February 26, 2013

Study Record Updates

• Last Update Posted (Estimate): February 26, 2013
• Last Update Submitted That Met QC Criteria: February 22, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Calcium Metabolism Disorders; Calcinosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Ergocalciferols
• Other Study ID Numbers: IBS-05; R01DK035423-19 (U.S. NIH Grant/Contract)