Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta

Osteogenesis Imperfecta Clinical Trial

Official title:

Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01713231
• Other study ID #: A02-M14-12A
• Status: Completed
• Phase: Phase 4
• First received: October 21, 2012
• Last updated: September 8, 2014
• Start date: September 2012
• Est. completion date: July 2014

Study information

• Verified date: September 2014
• Source: Shriners Hospitals for Children
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

• Overall Objective: To test the hypothesis that oral vitamin D supplementation at higher than currently prescribed doses has a beneficial effect on the skeleton of young patients with osteogenesis imperfecta (OI).

• Specific Aims: 1. To determine whether 12 months of high-dose vitamin D supplementation, compared to standard-dose vitamin D supplementation, increases areal bone mineral density z-scores at the lumbar spine. 2. To examine the effectiveness of high-dose vitamin D supplementation to increase trabecular and cortical bone mineral density at the radius. 3. To examine whether high-dose vitamin D supplementation has an effect on physiological determinants of bone mass (parathyroid hormone, activity of bone metabolism, muscle function).

• Background: In a preliminary cross-sectional study of 282 OI patients we observed an inverse relationship between serum 25-hydroxyvitamin D and parathyroid hormone levels and a positive relationship between circulating levels of 25-hydroxyvitamin D and lumbar spine areal bone mineral density z-scores. This suggested that high-dose vitamin D supplementation would have a beneficial effect on bone density. Most OI patients currently receive oral vitamin D supplementation of 400 International Units per day, but doses of 2000 International Units per day are safe and have been shown to be beneficial in studies on healthy adolescents.

• Study Design: This is a parallel-group double-blind randomized controlled trial of 12 months duration on 60 children and adolescents aged 6 to 19 years with a clinical diagnosis of OI. One group of 30 participants will be randomized to receive vitamin D3 at a dose of 2000 international units per day ('high-dose group'). The other group of 30 participants will be randomized to receive vitamin D3 at a dose of 400 international units per day ('standard-dose group'). Randomization will be stratified according to pubertal status and bisphosphonate treatment status.

• Clinical Relevance: The proposed study aims at direct improvements in the care of OI patients. If a simple and low-cost 'intervention' such as high-dose vitamin D supplementation can be shown to be effective in relieving some of the disease burden associated with OI, the benefit to OI patients worldwide would be substantial.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: July 2014
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 19 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of OI of any type.

Exclusion Criteria:

• Any condition that renders bone density measurements at the lumbar spine impossible. An example for this is prior spinal fusion surgery.

• Bisphosphonate therapy for less than two years duration.

• Use of medication, other than bisphosphonates, known to affect bone metabolism or 25OHD serum concentrations. Examples are anti-epileptics, active vitamin D metabolites, corticosteroids and thyroid hormones.

• Liver and renal disease known to interfere with vitamin D metabolism.

• Any other disorder of calcium and phosphate metabolism (apart from vitamin D deficiency) that might interfere with PTH.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Osteogenesis Imperfecta

Intervention

Dietary Supplement:
• standard-dose vitamin D (400IU per day)

• high-dose vitamin D (2000 IU per day)

Locations

Country	Name	City	State
Canada	Shriners Hospitals for Children-Canada	Montréal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Louis-Nicolas Veilleux Ph.D.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage change in lower extremity muscle power per body weight, as measured by jumping mechanography, relative to baseline.	A countermovement jump to maximal height ('single two-legged jump') will be evaluated. In patients who are unable to jump, the heel-rise test will be used to determine muscle power.	baseline and 12 months	No
Primary	Change in areal bone mineral density z-score of the lumbar spine	LS-aBMD z-score will be used as the primary outcome.The lumbar spine is the standard site of measurement both in the clinical follow up of OI patients .	at baseline and 12 months	No
Secondary	Change in trabecular and cortical volumetric bone mineral density z-scores at the radius, as measured by pQCT, relative to baseline.	Trabecular bone is analyzed at the distal radial metaphysis ('4% site'). Cortical bone is analyzed at the radial diaphysis ('65% site').	at baseline and at 12 months	No