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Optimal Vitamin D3 Supplementation Strategies for Acute Fracture Healing (Vita-Shock)

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ClinicalTrials.gov Identifier: NCT02786498
Recruitment Status : Active, not recruiting
First Posted : June 1, 2016
Last Update Posted : December 10, 2019
Sponsor:
Collaborator:
McMaster University
Information provided by (Responsible Party):
Gerard Slobogean, University of Maryland, Baltimore

Brief Summary:
The objective is to determine the effect of vitamin D3 supplementation on fracture healing at 3 months.

Condition or disease Intervention/treatment Phase
Fracture Drug: Vitamin D3 Other: Placebo Phase 2

Detailed Description:

Vitamin D supplements are increasingly being recommended to healthy adult fracture patients without an osteoporotic injury. Although this is a relatively new practice pattern, the basis for this adjunct therapy is grounded in the high hypovitaminosis D prevalence rates (up to 75%) among healthy adult fracture patients, and the strong biologic rationale for the role of vitamin D in fracture healing. Briefly, experimental animal studies have demonstrated that the concentration of vitamin D metabolites is higher at a fracture callus compared to the uninjured contralateral bone, vitamin D supplementation leads to decreased time to union and increased callus vascularity, and increases mechanical bone strength compared to controls. While evidence to confirm that vitamin D supplementation improves fracture healing in clinical studies does not exist, the pre-clinical data are compelling and worthy of further investigation.

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: A Blinded Exploratory Randomized Controlled Trial to Determine Optimal Vitamin D3 Supplementation Strategies for Acute Fracture Healing
Actual Study Start Date : November 21, 2016
Actual Primary Completion Date : August 2019
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: High Loading Dose
150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months.
Drug: Vitamin D3
Other: Placebo
Experimental: High Daily Dose
Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months.
Drug: Vitamin D3
Other: Placebo
Experimental: Low Daily Dose
Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months.
Drug: Vitamin D3
Other: Placebo
Placebo Comparator: Control Group
Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months.
Other: Placebo



Primary Outcome Measures :
  1. Fracture healing will be assessed clinically using FIX-IT [ Time Frame: 3 months post-injury ]
  2. Fracture healing will be assessed radiographically using RUST [ Time Frame: 3 months post-injury ]
  3. Fracture healing will be assessed biochemically using serum levels of the bone turnover marker CTX [ Time Frame: 3 months post-injury ]
  4. Fracture healing will be assessed biochemically using serum levels of the bone turnover marker PINP [ Time Frame: 3 months post-injury ]

Secondary Outcome Measures :
  1. Serum level of 25(OH)D [ Time Frame: Up to 3 months post-injury ]
    Correlations will be assessed between participants' 25(OH)D levels at enrolment, changes in 25(OH)D levels from enrolment to 3 months, and 25(OH)D levels at 3 months and fracture healing

  2. Patient self-report [ Time Frame: Up to 3 months post-injury ]
    Will measure adherence with vitamin D supplementation

  3. Adverse events [ Time Frame: Up to 12 months post-injury ]
    Will measure participant safety

  4. Serum levels of calcium [ Time Frame: Up to 12 months post-injury ]
    Will measure participant safety

  5. Serum levels of parathyroid hormone [ Time Frame: Up to 12 months post-injury ]
    Will measure participant safety

  6. Number of participants completing bloodwork and imaging outcome measures [ Time Frame: Up to 12 months post-injury ]
    Will measure adherence with the protocol



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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult men or women ages 18-50 years
  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:

  1. Osteoporosis
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02786498


Locations
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United States, Maryland
University of Maryland, R Adams Cowley Shock Trauma Center
Baltimore, Maryland, United States, 21201
Canada, Ontario
McMaster University, Center for Evidence-Based Orthopaedics
Hamilton, Ontario, Canada, L8L 8E7
Sponsors and Collaborators
University of Maryland, Baltimore
McMaster University
Investigators
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Principal Investigator: Gerard Slobogean, MD Unversity of Maryland
Principal Investigator: Sheila Sprague, PhD McMaster University

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Gerard Slobogean, Associate Professor of Orthopaedics, University of Maryland, Baltimore
ClinicalTrials.gov Identifier: NCT02786498     History of Changes
Other Study ID Numbers: HP-00069705
First Posted: June 1, 2016    Key Record Dates
Last Update Posted: December 10, 2019
Last Verified: December 2019
Keywords provided by Gerard Slobogean, University of Maryland, Baltimore:
Tibial Shaft
Tibia
Femoral Shaft
Femur
Vitamin D
Fracture Healing
Additional relevant MeSH terms:
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Fractures, Bone
Wounds and Injuries
Vitamin D
Ergocalciferols
Cholecalciferol
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents