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

Sponsor
University of Maryland, Baltimore (Other)
Overall Status
Completed
CT.gov ID
NCT02786498
Collaborator
McMaster University (Other)
102
Enrollment
2
Locations
4
Arms
60.3
Actual Duration (Months)
51
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

Study Description

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
  • 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
102 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Other
Official Title:
A Blinded Exploratory Randomized Controlled Trial (RCT) to Determine Optimal Vitamin D3 Supplementation Strategies for Acute Fracture Healing
Actual Study Start Date :
Nov 21, 2016
Actual Primary Completion Date :
Aug 1, 2019
Actual Study Completion Date :
Dec 1, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Fracture Healing Will be Assessed Clinically Using Function IndeX for Trauma (FIX-IT) [3 months post-injury]

    FIX-IT is a standardized measure of weight-bearing and pain in patients with lower extremity fractures, specifically tibia and femur fractures. The FIX-IT score ranges from 0 to 12 points in 2 domains: the ability to bear weight (maximum 6 points) and pain at the fracture site (maximum 6 points) The ability to bear weight is assessed through the single-leg stand and ambulation procedures. Pain is assessed through palpation and stress procedures. The scores in both domains, which are weighted equally, are summed to obtain the final total score; the maximum score of 12 indicates the highest level of function.

  2. Fracture Healing Will be Assessed Radiographically Using Radiographic Union Score for Tibial Fractures (RUST) [3 months post-injury]

    Radiographic fracture healing was measured using the Radiographic Union Score for Tibial fractures (RUST), which assesses the presence of bridging callus or a persistent fracture line on each of four cortices. This method evaluates two orthogonal radiographic views; each cortex is attributed points ranging from 1 to 3. A fracture in the immediate postoperative period will receive the minimum score, 4, (1 point for each of the four cortices) and a fully consolidated or healed fracture will be assigned the maximum score, 12 (3 points on each of the four cortices).

  3. Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker (BTM) C-terminal Telopeptide of Type I Collagen (CTX) [3 months post-injury]

    The BTM C-terminal telopeptide of type I collagen (CTX). CTX is a marker of bone resorption. Clinically important changes in the CTX markers are unknown; however, in a previous study of tibia fracture healing, Veitch et al observed concentrations of both bone turnover markers approximately 100% greater than baseline values.43 Given the large changes observed in these bone turnover markers, the same criteria will be applied for identifying a potentially clinically beneficial regimen and remain powered to detect a mean difference of 20% (SD 30%).

  4. Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker N-terminal Propeptide of Type I Procollagen (P1NP) [3 months post-injury]

    P1NP is a bone-formation marker and prior research has found that it is highest at 12 weeks after fractures of the tibial shaft and proximal femur.

Secondary Outcome Measures

  1. Serum Level of 25(OH)D [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. Number of Participants With Adherence With Vitamin D Supplementation [Up to 3 months post-injury]

    Will measure adherence with vitamin D supplementation based on participants self report at the 6 week and 3 month visits.

  3. Number of Participants With Adverse Events (AE) [Up to 12 months post-injury]

    A count of the participants who experienced adverse events will measure participant safety

  4. Serum Levels of Calcium [Up to 3 months post-injury]

    Will measure participant safety

  5. Serum Levels of Parathyroid Hormone [Up to 3 months post-injury]

    Helps the body to maintain stable levels of calcium in the blood

  6. Count of Participants Who Completed Blood Measures [Up to 3 months post-injury]

    Will measure participants adherence to the blood measures of the protocol.

  7. Count of Participants Who Completed Radiographic Imaging Measures [up to 12 months]

    Count of participants who completed radiographic imaging measures to determine participant protocol adherence and assists with identifying healing status

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 50 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Maryland, R Adams Cowley Shock Trauma Center Baltimore Maryland United States 21201
2 McMaster University, Center for Evidence-Based Orthopaedics Hamilton Ontario Canada L8L 8E7

Sponsors and Collaborators

  • University of Maryland, Baltimore
  • McMaster University

Investigators

  • Principal Investigator: Gerard Slobogean, MD, University of Maryland
  • Principal Investigator: Sheila Sprague, PhD, McMaster University

Study Documents (Full-Text)

More Information

Publications

Responsible Party:
Gerard Slobogean, Associate Professor of Orthopaedics, University of Maryland, Baltimore
ClinicalTrials.gov Identifier:
NCT02786498
Other Study ID Numbers:
  • HP-00069705
First Posted:
Jun 1, 2016
Last Update Posted:
Mar 31, 2022
Last Verified:
Mar 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Gerard Slobogean, Associate Professor of Orthopaedics, University of Maryland, Baltimore
Tibial Shaft
Tibia
Femoral Shaft
Femur
Vitamin D
Fracture Healing
Additional relevant MeSH terms:
Fractures, Bone
Vitamin D
Cholecalciferol

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title High Loading Dose High Daily Dose Low Daily Dose Control Group
Arm/Group Description 150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months. Placebo
Period Title: Overall Study
STARTED 27 24 24 27
COMPLETED 25 24 24 26
NOT COMPLETED 2 0 0 1

Baseline Characteristics

Arm/Group Title High Loading Dose High Daily Dose Low Daily Dose Control Group Total
Arm/Group Description 150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months. Placebo Total of all reporting groups
Overall Participants 27 24 24 27 102
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
0
0%
0
0%
Between 18 and 65 years
27
100%
24
100%
24
100%
27
100%
102
100%
>=65 years
0
0%
0
0%
0
0%
0
0%
0
0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
27.4
(8.1)
28.8
(7.3)
31.1
(9.8)
31.3
(7.9)
29.65
(8.28)
Sex: Female, Male (Count of Participants)
Female
13
48.1%
5
20.8%
8
33.3%
6
22.2%
32
31.4%
Male
14
51.9%
19
79.2%
16
66.7%
21
77.8%
70
68.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
2
7.4%
2
8.3%
0
0%
1
3.7%
5
4.9%
Not Hispanic or Latino
25
92.6%
22
91.7%
24
100%
26
96.3%
97
95.1%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
0
0%
Asian
0
0%
0
0%
1
4.2%
1
3.7%
2
2%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
0
0%
Black or African American
11
40.7%
11
45.8%
10
41.7%
15
55.6%
47
46.1%
White
14
51.9%
11
45.8%
13
54.2%
10
37%
48
47.1%
More than one race
2
7.4%
2
8.3%
0
0%
1
3.7%
5
4.9%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
Region of Enrollment (participants) [Number]
United States
27
100%
24
100%
24
100%
27
100%
102
100%
Smoking status (Count of Participants)
Current Smoker
10
37%
6
25%
7
29.2%
14
51.9%
37
36.3%
Previous Smoker
1
3.7%
3
12.5%
2
8.3%
0
0%
6
5.9%
Non-Smoker
16
59.3%
15
62.5%
15
62.5%
13
48.1%
59
57.8%
Fractured bone (Tibia) (Count of Participants)
Count of Participants [Participants]
11
40.7%
9
37.5%
10
41.7%
11
40.7%
41
40.2%
Association for the Study of Internal fixation /Orthopaedic Trauma AssociationClassification (AO/OTA (Count of Participants)
AO/OTA Class 32.A
10
37%
6
25%
9
37.5%
9
33.3%
34
33.3%
AO/OTA Class 32.B
4
14.8%
4
16.7%
5
20.8%
3
11.1%
16
15.7%
AO/OTA Class 32.C
2
7.4%
4
16.7%
2
8.3%
4
14.8%
12
11.8%
AO/OTA Class 42.A
7
25.9%
3
12.5%
3
12.5%
6
22.2%
19
18.6%
AO/OTA Class 42.B
3
11.1%
3
12.5%
4
16.7%
3
11.1%
13
12.7%
AO/OTA Class 42.C
1
3.7%
4
16.7%
1
4.2%
2
7.4%
8
7.8%
Vitamin D3 deficient (25(OH)D Serum Levels ,20 ng/mL) (Count of Participants)
Count of Participants [Participants]
16
59.3%
11
45.8%
12
50%
17
63%
56
54.9%

Outcome Measures

1. Primary Outcome
Title Fracture Healing Will be Assessed Clinically Using Function IndeX for Trauma (FIX-IT)
Description FIX-IT is a standardized measure of weight-bearing and pain in patients with lower extremity fractures, specifically tibia and femur fractures. The FIX-IT score ranges from 0 to 12 points in 2 domains: the ability to bear weight (maximum 6 points) and pain at the fracture site (maximum 6 points) The ability to bear weight is assessed through the single-leg stand and ambulation procedures. Pain is assessed through palpation and stress procedures. The scores in both domains, which are weighted equally, are summed to obtain the final total score; the maximum score of 12 indicates the highest level of function.
Time Frame 3 months post-injury

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title High Loading Dose High Daily Dose Low Daily Dose Control Group
Arm/Group Description 150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months. Placebo
Measure Participants 27 24 24 27
Mean (Standard Deviation) [scores on a scale]
10.1
(2.5)
9.7
(2.8)
9.3
(3.3)
9.0
(2.9)
2. Primary Outcome
Title Fracture Healing Will be Assessed Radiographically Using Radiographic Union Score for Tibial Fractures (RUST)
Description Radiographic fracture healing was measured using the Radiographic Union Score for Tibial fractures (RUST), which assesses the presence of bridging callus or a persistent fracture line on each of four cortices. This method evaluates two orthogonal radiographic views; each cortex is attributed points ranging from 1 to 3. A fracture in the immediate postoperative period will receive the minimum score, 4, (1 point for each of the four cortices) and a fully consolidated or healed fracture will be assigned the maximum score, 12 (3 points on each of the four cortices).
Time Frame 3 months post-injury

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title High Loading Dose High Daily Dose Low Daily Dose Control Group
Arm/Group Description 150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months. Placebo
Measure Participants 27 24 24 27
Mean (Standard Deviation) [Score on a scale 4-12]
11.0
(2.8)
11.3
(2.9)
11.0
(3.0)
10.4
(2.5)
3. Primary Outcome
Title Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker (BTM) C-terminal Telopeptide of Type I Collagen (CTX)
Description The BTM C-terminal telopeptide of type I collagen (CTX). CTX is a marker of bone resorption. Clinically important changes in the CTX markers are unknown; however, in a previous study of tibia fracture healing, Veitch et al observed concentrations of both bone turnover markers approximately 100% greater than baseline values.43 Given the large changes observed in these bone turnover markers, the same criteria will be applied for identifying a potentially clinically beneficial regimen and remain powered to detect a mean difference of 20% (SD 30%).
Time Frame 3 months post-injury

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title High Loading Dose High Daily Dose Low Daily Dose Control Group
Arm/Group Description 150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months. Placebo
Measure Participants 27 24 24 27
Mean (Standard Deviation) [ng/mL]
0.59
(0.75)
0.79
(0.93)
0.67
(0.64)
0.78
(0.97)
4. Primary Outcome
Title Fracture Healing Will be Assessed Biochemically Using Serum Levels of the Bone Turnover Marker N-terminal Propeptide of Type I Procollagen (P1NP)
Description P1NP is a bone-formation marker and prior research has found that it is highest at 12 weeks after fractures of the tibial shaft and proximal femur.
Time Frame 3 months post-injury

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title High Loading Dose High Daily Dose Low Daily Dose Control Group
Arm/Group Description 150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months. Placebo
Measure Participants 27 24 24 27
Mean (Standard Deviation) [ng/mL]
160.9
(140.1)
187.8
(129.3)
166.7
(115.8)
140.7
(124.7)
5. Secondary Outcome
Title Serum Level of 25(OH)D
Description 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
Time Frame Up to 3 months post-injury

Outcome Measure Data

Analysis Population Description
Serum 25(OH)D Concentration by Treatment Group
Arm/Group Title High Loading Dose High Daily Dose Low Daily Dose Control Group
Arm/Group Description 150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months. Placebo
Measure Participants 27 24 24 27
Baseline
18.8
(7.8)
20.7
(9.6)
19.7
(7.9)
17.3
(7.5)
Week 6
39.3
(17.8)
38.4
(18.6)
35.5
(22.5)
26.1
(15.4)
Month 3
39.9
(17.9)
28.2
(20.7)
38.1
(19.8)
23.1
(19.0)
6. Secondary Outcome
Title Number of Participants With Adherence With Vitamin D Supplementation
Description Will measure adherence with vitamin D supplementation based on participants self report at the 6 week and 3 month visits.
Time Frame Up to 3 months post-injury

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title High Loading Dose High Daily Dose Low Daily Dose Control Group
Arm/Group Description 150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months. Placebo
Measure Participants 27 24 24 27
6 Weeks
19
70.4%
20
83.3%
18
75%
22
81.5%
3 Months
21
77.8%
19
79.2%
19
79.2%
20
74.1%
7. Secondary Outcome
Title Number of Participants With Adverse Events (AE)
Description A count of the participants who experienced adverse events will measure participant safety
Time Frame Up to 12 months post-injury

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title High Loading Dose High Daily Dose Low Daily Dose Control Group
Arm/Group Description 150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months. Placebo
Measure Participants 27 24 24 27
Count of Participants [Participants]
9
33.3%
10
41.7%
11
45.8%
14
51.9%
8. Secondary Outcome
Title Serum Levels of Calcium
Description Will measure participant safety
Time Frame Up to 3 months post-injury

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title High Loading Dose High Daily Dose Low Daily Dose Control Group
Arm/Group Description 150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months. Placebo
Measure Participants 27 24 24 27
baseline
9.1
(0.6)
8.8
(0.7)
8.3
(1.8)
9.0
(0.6)
Week 6
9.6
(0.3)
9.6
(0.3)
9.6
(0.4)
9.6
(0.5)
Month 3
9.5
(0.3)
9.6
(0.5)
9.7
(0.4)
9.6
(0.3)
9. Secondary Outcome
Title Serum Levels of Parathyroid Hormone
Description Helps the body to maintain stable levels of calcium in the blood
Time Frame Up to 3 months post-injury

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title High Loading Dose High Daily Dose Low Daily Dose Control Group
Arm/Group Description 150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months. Placebo
Measure Participants 27 24 24 27
Baseline
69.6
(39.0)
64.7
(37.2)
67.8
(35.1)
60.3
(31.1)
Week 6
41.9
(47.7)
28.8
(32.2)
68.0
(63.2)
43.6
(47.7)
Month 3
42.4
(39.6)
71.0
(68.0)
63.1
(48.1)
74.6
(60.6)
10. Secondary Outcome
Title Count of Participants Who Completed Blood Measures
Description Will measure participants adherence to the blood measures of the protocol.
Time Frame Up to 3 months post-injury

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title High Loading Dose High Daily Dose Low Daily Dose Control Group
Arm/Group Description 150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months. Placebo
Measure Participants 27 24 24 27
baseline
26
96.3%
24
100%
24
100%
26
96.3%
Week 6
21
77.8%
20
83.3%
15
62.5%
22
81.5%
Month 3
19
70.4%
11
45.8%
17
70.8%
15
55.6%
11. Secondary Outcome
Title Count of Participants Who Completed Radiographic Imaging Measures
Description Count of participants who completed radiographic imaging measures to determine participant protocol adherence and assists with identifying healing status
Time Frame up to 12 months

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title High Loading Dose High Daily Dose Low Daily Dose Control Group
Arm/Group Description 150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months. Placebo
Measure Participants 27 24 24 27
Baseline
27
100%
24
100%
24
100%
27
100%
Week 6
24
88.9%
22
91.7%
17
70.8%
19
70.4%
Month 3
21
77.8%
17
70.8%
20
83.3%
16
59.3%
Month 6
16
59.3%
11
45.8%
13
54.2%
13
48.1%
Month 9
4
14.8%
4
16.7%
6
25%
5
18.5%
Month 12
6
22.2%
3
12.5%
4
16.7%
5
18.5%

Adverse Events

Time Frame 12 months after initial injury
Adverse Event Reporting Description An Adverse Event (AE) is any symptom, sign, illness, or experience that develops or worsens in severity during the course of this study. AEs are classified as serious or non-serious.
Arm/Group Title High Loading Dose High Daily Dose Low Daily Dose Control Group
Arm/Group Description 150,000 IU loading dose vitamin D3 at enrolment and 6 weeks, plus daily dose placebo for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 4,000 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus 600 IU vitamin D3 per day for 3 months. Vitamin D3 Placebo Loading dose placebo at enrolment and 6 weeks, plus daily dose placebo for 3 months. Placebo
All Cause Mortality
High Loading Dose High Daily Dose Low Daily Dose Control Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/27 (0%) 0/24 (0%) 0/24 (0%) 0/27 (0%)
Serious Adverse Events
High Loading Dose High Daily Dose Low Daily Dose Control Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/27 (0%) 0/24 (0%) 0/24 (0%) 0/27 (0%)
Other (Not Including Serious) Adverse Events
High Loading Dose High Daily Dose Low Daily Dose Control Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 9/27 (33.3%) 10/24 (41.7%) 11/24 (45.8%) 14/27 (51.9%)
Blood and lymphatic system disorders
Sickle Cell Crisis 0/27 (0%) 0 0/24 (0%) 0 3/24 (12.5%) 3 0/27 (0%) 0
Gastrointestinal disorders
Gastrointestinal 0/27 (0%) 0 1/24 (4.2%) 1 0/24 (0%) 0 1/27 (3.7%) 1
General disorders
Accident/Fall 0/27 (0%) 0 0/24 (0%) 0 1/24 (4.2%) 1 1/27 (3.7%) 1
Infections and infestations
Sinus Infection 0/27 (0%) 0 1/24 (4.2%) 1 0/24 (0%) 0 0/27 (0%) 0
Cellulitus 0/27 (0%) 0 0/24 (0%) 0 1/24 (4.2%) 1 0/27 (0%) 0
Musculoskeletal and connective tissue disorders
Fracture Healing Complication 5/27 (18.5%) 5 4/24 (16.7%) 4 5/24 (20.8%) 5 6/27 (22.2%) 6
Non-study Fracture 1/27 (3.7%) 1 0/24 (0%) 0 0/24 (0%) 0 2/27 (7.4%) 2
Retained Foreign Object 1/27 (3.7%) 1 0/24 (0%) 0 0/24 (0%) 0 1/27 (3.7%) 1
Re-operations for fracture healing complications 4/27 (14.8%) 4 4/24 (16.7%) 4 2/24 (8.3%) 2 7/27 (25.9%) 7
Pregnancy, puerperium and perinatal conditions
Miscarriage 0/27 (0%) 0 1/24 (4.2%) 1 0/24 (0%) 0 0/27 (0%) 0
Respiratory, thoracic and mediastinal disorders
Recurrent Pneumothorax 0/27 (0%) 0 0/24 (0%) 0 1/24 (4.2%) 1 0/27 (0%) 0
Vascular disorders
Vascular 2/27 (7.4%) 2 3/24 (12.5%) 3 0/24 (0%) 0 3/27 (11.1%) 3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Dr Gerard Slobogean
Organization University of Maryland Baltimore, School of Medicine, Department of Orthopaedics
Phone 410-28-6280
Email gslobogean@som.umaryland.edu
Responsible Party:
Gerard Slobogean, Associate Professor of Orthopaedics, University of Maryland, Baltimore
ClinicalTrials.gov Identifier:
NCT02786498
Other Study ID Numbers:
  • HP-00069705
First Posted:
Jun 1, 2016
Last Update Posted:
Mar 31, 2022
Last Verified:
Mar 1, 2022