How Bone is Made in Children Receiving Dialysis

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
Regulation of Bone Mineralization in Renal Osteodystrophy

Conditions
-----------------
Bone Mineralization Defect

Intervention / Treatment
-----------------
* Drug: Vitamin D2


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment with vitamin D2<br>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<br>* These patients will receive standard of care vitamin D 1,25 therapy with intervention of vitamin D2<br>* Other names: Ergocalciferol;|
| No Intervention: Standard of Care<br>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 |