How Bone is Made in Children Receiving Dialysis

University of California, Los Angeles (UCLA)

Status and phase: Unknown; Phase 4

Conditions: Bone Mineralization Defect

Treatments: Drug: Vitamin D2

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01799317

R01DK035423-19 (U.S. NIH Grant/Contract)

IBS-05

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 6 to 21 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Treatment with vitamin D2

Active Comparator group

Description:

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

Treatment:

Drug: Vitamin D2

Standard of Care

No Intervention group

Description:

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