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

• ClinicalTrials.gov Identifier: NCT01713231
• Recruitment Status: Completed
• First Posted: October 24, 2012
• Last Update Posted: September 9, 2014
• Sponsor: Louis-Nicolas Veilleux Ph.D.
• Information provided by (Responsible Party): Louis-Nicolas Veilleux Ph.D., Shriners Hospitals for Children

Tracking Information

• First Submitted Date: October 21, 2012
• First Posted Date: October 24, 2012
• Last Update Posted Date: September 9, 2014
• Study Start Date: September 2012
• Actual Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 21, 2012)

Change in areal bone mineral density z-score of the lumbar spine [ Time Frame: at baseline and 12 months ]

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 .

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 21, 2012)

Change in trabecular and cortical volumetric bone mineral density z-scores at the radius, as measured by pQCT, relative to baseline. [ Time Frame: at baseline and at 12 months ]

Trabecular bone is analyzed at the distal radial metaphysis ('4% site'). Cortical bone is analyzed at the radial diaphysis ('65% site').

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: October 21, 2012)

Percentage change in lower extremity muscle power per body weight, as measured by jumping mechanography, relative to baseline. [ Time Frame: baseline and 12 months ]

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.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Supportive Care
• Condition: Osteogenesis Imperfecta

Intervention

• Dietary Supplement: standard-dose vitamin D (400IU per day)
• Dietary Supplement: high-dose vitamin D (2000 IU per day)

Study Arms

• Active Comparator: 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').
  Intervention: Dietary Supplement: standard-dose vitamin D (400IU per day)
• Experimental: 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').
  Intervention: Dietary Supplement: high-dose vitamin D (2000 IU per day)

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 21, 2012): 60
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: July 2014
• Actual Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 19 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT01713231
• Other Study ID Numbers: A02-M14-12A
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Louis-Nicolas Veilleux Ph.D., Shriners Hospitals for Children
• Original Responsible Party: Same as current
• Current Study Sponsor: Louis-Nicolas Veilleux Ph.D.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Shriners Hospitals for Children
• Verification Date: September 2014