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

NCT ID: NCT01713231

Last Updated: 2014-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2014-07-31

Brief 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.

Conditions

Osteogenesis Imperfecta

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: TRIPLE

Study Groups

standard-dose vitamin D

one group of 30 participants will be randomized to receive vitamin D3 at a dose of 400 international units per day ('standard-dose group').

Group Type: ACTIVE_COMPARATOR

standard-dose vitamin D (400IU per day)

Intervention Type: DIETARY_SUPPLEMENT

high-dose vitamin D

One group of 30 participants will be randomized to receive vitamin D3 at a dose of 2000 international units per day ('high-dose group').

Group Type: EXPERIMENTAL

high-dose vitamin D (2000 IU per day)

Intervention Type: DIETARY_SUPPLEMENT

Interventions

standard-dose vitamin D (400IU per day)

Intervention Type: DIETARY_SUPPLEMENT

high-dose vitamin D (2000 IU per day)

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Louis-Nicolas Veilleux Ph.D.

OTHER

Sponsor Role: lead

Responsible Party

Louis-Nicolas Veilleux Ph.D.

postdoctoral fellow

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Shriners Hospitals for Children-Canada

Montreal, Quebec, Canada

Countries

Canada

References

Plante L, Veilleux LN, Glorieux FH, Weiler H, Rauch F. Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial. Bone. 2016 May;86:36-42. doi: 10.1016/j.bone.2016.02.013. Epub 2016 Feb 24.

Reference Type: DERIVED

PMID: 26924265 (View on PubMed)

Other Identifiers

A02-M14-12A

Identifier Type: -

Identifier Source: org_study_id