Optimal Vitamin D3 Supplementation Strategies for Acute Fracture Healing
NCT ID: NCT02786498
Last Updated: 2022-03-31
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
102 participants
INTERVENTIONAL
2016-11-21
2021-12-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Vitamin D Supplementation and Tibia Fracture. Does it Improve Healing Rate?
NCT03232216
Vitamin D3 Supplementation and Stress Fracture Occurrence in High-Risk Collegiate Athletes
NCT03395171
Vitamin D Supplement for Patients With Tibial Fracture
NCT01955577
The Vitamin K2 and D3 Intervention Trial in Children and Adolescents With the Low-energy Fractures
NCT03871322
The Effect of Vitamin D and Calcium Supplementation on the Prevention of Stress Fractures.
NCT05186194
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
With modern orthopaedic surgical care, rates of complications following tibia and femoral shaft fractures can be as high as 15%. Complications, including delayed union, nonunion, or infection often require secondary surgical procedures and result in profound personal and societal economic costs. While surgeons continue to seek advances in surgical technique, it is becoming increasingly obvious that innovations in orthopaedic techniques or implants are unlikely to eliminate complications. As a result, considerable attention is currently focused on adjunct biologic therapies, such as vitamin D.
A recent survey of 397 orthopaedic surgeons showed that only 26% routinely prescribe vitamin D supplementation to adult fracture patients. Of the 93 surgeons who indicated that they routinely prescribe vitamin D supplementation, 29 different dosing regimens were described ranging from low daily doses of 400 IU to loading doses of 600,000 IU. This suggests a high level of clinical uncertainty surrounding the use and optimal dose of vitamin D supplementation in adult fracture patients. If vitamin D supplementation improves fracture healing outcomes, then there is a large opportunity to increase its use; however, before widespread adoption occurs, research is needed to optimize the dosing strategy, establish the dosing safety in the immobilized fracture healing population, and overcome potential medication adherence issues among the often marginalized patients that suffer trauma.
The long-term goal of our research program is to conduct a large phase III RCT to determine which dose of vitamin D3 supplementation optimally improves acute fracture healing outcomes in healthy adult patients (18-50 years). The current proposed phase II exploratory trial will perform important preliminary work to test the central hypothesis that vitamin D3 dose and timing of administration is critical for improving fracture healing at 3 months. This trial will also inform the feasibility of the large phase III RCT.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
OTHER
TRIPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
High Loading Dose
150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months.
Vitamin D3
Placebo
High Daily Dose
Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months.
Vitamin D3
Placebo
Low Daily Dose
Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months.
Vitamin D3
Placebo
Control Group
Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months.
Placebo
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Vitamin D3
Placebo
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Closed or low grade open (Gustilo type I or II) tibial or femoral shaft fracture
3. Fracture treated with a reamed, locked, intramedullary nail
4. Acute fracture (enrolled within 7 days of injury)
5. Provision of informed consent.
Exclusion Criteria
2. Stress fractures
3. Elevated serum calcium (\>10.5 mg/dL)
4. Atypical femur fractures as defined by American Society for Bone and Mineral Research (ASBMR) criteria
5. Pathological fractures secondary to neoplasm or other bone lesion
6. Patients with known or likely undiagnosed disorders of bone metabolism such as Paget's disease, osteomalacia, osteopetrosis, osteogenesis imperfecta etc.
7. Patients with hyperhomocysteinemia
8. Patients with an allergy to vitamin D or another contraindication to being prescribed vitamin D
9. Patients currently taking an over the counter multivitamin that contains vitamin D and are unable or unwilling to discontinue its use for this study
10. Patients who will likely have problems, in the judgment of the investigators, with maintaining follow-up
11. Pregnancy
12. Patients who are incarcerated
13. Patients who are not expected to survive their injuries
14. Other lower extremity injuries that prevent bilateral full weight-bearing by 6 weeks post-fracture.
18 Years
50 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
McMaster University
OTHER
University of Maryland, Baltimore
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Gerard Slobogean
Associate Professor of Orthopaedics
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Gerard Slobogean, MD
Role: PRINCIPAL_INVESTIGATOR
University of Maryland
Sheila Sprague, PhD
Role: PRINCIPAL_INVESTIGATOR
McMaster University
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of Maryland, R Adams Cowley Shock Trauma Center
Baltimore, Maryland, United States
McMaster University, Center for Evidence-Based Orthopaedics
Hamilton, Ontario, Canada
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Sprague S, Petrisor B, Scott T, Devji T, Phillips M, Spurr H, Bhandari M, Slobogean GP. What Is the Role of Vitamin D Supplementation in Acute Fracture Patients? A Systematic Review and Meta-Analysis of the Prevalence of Hypovitaminosis D and Supplementation Efficacy. J Orthop Trauma. 2016 Feb;30(2):53-63. doi: 10.1097/BOT.0000000000000455.
Omeroglu S, Erdogan D, Omeroglu H. Effects of single high-dose vitamin D3 on fracture healing. An ultrastructural study in healthy guinea pigs. Arch Orthop Trauma Surg. 1997;116(1-2):37-40.
Jingushi S, Iwaki A, Higuchi O, Azuma Y, Ohta T, Shida JI, Izumi T, Ikenoue T, Sugioka Y, Iwamoto Y. Serum 1alpha,25-dihydroxyvitamin D3 accumulates into the fracture callus during rat femoral fracture healing. Endocrinology. 1998 Apr;139(4):1467-73. doi: 10.1210/endo.139.4.5883.
Lidor C, Dekel S, Edelstein S. The metabolism of vitamin D3 during fracture healing in chicks. Endocrinology. 1987 Jan;120(1):389-93. doi: 10.1210/endo-120-1-389.
Lidor C, Dekel S, Hallel T, Edelstein S. Levels of active metabolites of vitamin D3 in the callus of fracture repair in chicks. J Bone Joint Surg Br. 1987 Jan;69(1):132-6. doi: 10.1302/0301-620X.69B1.3029136.
Omeroglu H, Ates Y, Akkus O, Korkusuz F, Bicimoglu A, Akkas N. Biomechanical analysis of the effects of single high-dose vitamin D3 on fracture healing in a healthy rabbit model. Arch Orthop Trauma Surg. 1997;116(5):271-4. doi: 10.1007/BF00390051.
Study to Prospectively Evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures Investigators; Bhandari M, Guyatt G, Tornetta P 3rd, Schemitsch EH, Swiontkowski M, Sanders D, Walter SD. Randomized trial of reamed and unreamed intramedullary nailing of tibial shaft fractures. J Bone Joint Surg Am. 2008 Dec;90(12):2567-78. doi: 10.2106/JBJS.G.01694.
Duan X, Al-Qwbani M, Zeng Y, Zhang W, Xiang Z. Intramedullary nailing for tibial shaft fractures in adults. Cochrane Database Syst Rev. 2012 Jan 18;1(1):CD008241. doi: 10.1002/14651858.CD008241.pub2.
Bhandari M, Guyatt GH, Tong D, Adili A, Shaughnessy SG. Reamed versus nonreamed intramedullary nailing of lower extremity long bone fractures: a systematic overview and meta-analysis. J Orthop Trauma. 2000 Jan;14(1):2-9. doi: 10.1097/00005131-200001000-00002.
Bonafede M, Espindle D, Bower AG. The direct and indirect costs of long bone fractures in a working age US population. J Med Econ. 2013;16(1):169-78. doi: 10.3111/13696998.2012.737391. Epub 2012 Oct 22.
Antonova E, Le TK, Burge R, Mershon J. Tibia shaft fractures: costly burden of nonunions. BMC Musculoskelet Disord. 2013 Jan 26;14:42. doi: 10.1186/1471-2474-14-42.
Kanakaris NK, Giannoudis PV. The health economics of the treatment of long-bone non-unions. Injury. 2007 May;38 Suppl 2:S77-84. doi: 10.1016/s0020-1383(07)80012-x.
Bhandari M, Schemitsch EH. Stimulation of fracture healing: osteobiologics, bone stimulators, and beyond. J Orthop Trauma. 2010 Mar;24 Suppl 1:S1. doi: 10.1097/BOT.0b013e3181d2d683. No abstract available.
Marsell R, Einhorn TA. Emerging bone healing therapies. J Orthop Trauma. 2010 Mar;24 Suppl 1:S4-8. doi: 10.1097/BOT.0b013e3181ca3fab.
Schoelles K, Snyder D, Kaczmarek J, Kuserk E, Erinoff E, Turkelson C, Coates V. The Role of Bone Growth Stimulating Devices and Orthobiologics in Healing Nonunion Fractures [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2005 Sep 21. Available from http://www.ncbi.nlm.nih.gov/books/NBK285118/
Veitch SW, Findlay SC, Hamer AJ, Blumsohn A, Eastell R, Ingle BM. Changes in bone mass and bone turnover following tibial shaft fracture. Osteoporos Int. 2006;17(3):364-72. doi: 10.1007/s00198-005-2025-y. Epub 2005 Dec 15.
Hojsager FD, Rand MS, Pedersen SB, Nissen N, Jorgensen NR. Fracture-induced changes in biomarkers CTX, PINP, OC, and BAP-a systematic review. Osteoporos Int. 2019 Dec;30(12):2381-2389. doi: 10.1007/s00198-019-05132-1. Epub 2019 Aug 24.
Sprague S, Bzovsky S, Connelly D, Thabane L, Adachi JD, Slobogean GP; Vita-Shock Investigators. Study protocol: design and rationale for an exploratory phase II randomized controlled trial to determine optimal vitamin D3 supplementation strategies for acute fracture healing. Pilot Feasibility Stud. 2019 Nov 22;5:135. doi: 10.1186/s40814-019-0524-4. eCollection 2019.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
HP-00069705
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.