Clinical trial NCT01713231: Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta
Official title: Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Osteogenesis Imperfecta
Keywords: osteogenesis imperfecta
high-dose vitamin D
bone density
muscle function
Lead sponsor: Shriners Hospitals for Children
Sponsor class: OTHER
First posted: 2012-10-24
Enrollment: 60
Sex: ALL
Minimum age (years): 6
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.


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.

Primary outcomes:
measure: Change in areal bone mineral density z-score of the lumbar spine
timeFrame: at baseline and 12 months
Secondary outcomes:
measure: Change in trabecular and cortical volumetric bone mineral density z-scores at the radius, as measured by pQCT, relative to baseline.
timeFrame: at baseline and at 12 months
Other outcomes:
measure: Percentage change in lower extremity muscle power per body weight, as measured by jumping mechanography, relative to baseline.
timeFrame: baseline and 12 months
Locations:
city: Montréal
country: Canada
facility: Shriners Hospitals for Children-Canada
state: Quebec
Study officials:
References:
citation: 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.