How Bone is Made in Children Receiving Dialysis

• ClinicalTrials.gov Identifier: NCT01799317
• Recruitment Status: Unknown
• First Posted: February 26, 2013
• Last Update Posted: February 26, 2013
• Sponsor: University of California, Los Angeles
• Collaborators: Children's Hospital Los Angeles; Loma Linda University; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Isidro Salusky, MD, University of California, Los Angeles

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Bone Mineralization Defect	Drug: Vitamin D2	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Regulation of Bone Mineralization in Renal Osteodystrophy
• Study Start Date: March 2009
• Estimated Primary Completion Date: June 2014
• Estimated Study Completion Date: June 2014

Arms and Interventions

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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Improvement of bone mineralization defect demonstrated by bone histomorphometry [ Time Frame: 8 months ]
   Iliac crest bone biopsy pre and post treatment with vitamin D2

Secondary Outcome Measures :

1. Radiographic improvement of skeletal abnormalities associated with renal osteodystrophy [ Time Frame: 8 months ]
   We will compare skeletal lesions identified through radiographic studies with bone histomorphometry pre and post treatment with vitamin D2

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Isidro Salusky, MD; 310.206.6987; isalusky@mednet.ucla.edu

Locations

United States, California

Loma Linda University; Recruiting

Loma Linda, California, United States, 92354

Contact: Shobbha Sahney, MD 909-558-8242 ssahney@llu.edu

Principal Investigator: Shobha Sahney, MD

Childrens Hospital Los Angeles; Recruiting

Los Angeles, California, United States, 90027

Contact: Kevin Lemley, MD 323-361-2295 klemley@chla.usc.edu

Principal Investigator: Kevin Lemley, MD

Sponsors and Collaborators

University of California, Los Angeles

Children's Hospital Los Angeles

Loma Linda University

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Isidro Salusky, MD; University of California, Los Angeles

More Information

• Responsible Party: Isidro Salusky, MD, Principal Investigator, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT01799317
• Other Study ID Numbers: IBS-05; R01DK035423-19 ( U.S. NIH Grant/Contract )
• First Posted: February 26, 2013
• Last Update Posted: February 26, 2013
• Last Verified: February 2013

Additional relevant MeSH terms:

Calcinosis; Calcium Metabolism Disorders; Metabolic Diseases; Vitamin D; Ergocalciferols; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents